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Fused Pyridine Derivatives: Synthesis and Biological Activities

Written By

Huseyin Istanbullu, Gulsah Bayraktar and Merve Saylam

Submitted: 14 August 2022 Reviewed: 01 September 2022 Published: 13 October 2022

DOI: 10.5772/intechopen.107537

Exploring Chemistry with Pyridine Derivatives IntechOpen
Exploring Chemistry with Pyridine Derivatives Edited by Satyanarayan Pal

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Exploring Chemistry with Pyridine Derivatives

Edited by Satyanarayan Pal

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Abstract

Five-membered heteroaromatic ring fused pyridine derivatives are of increasing interest in drug design and medicinal chemistry. The structural similarity of many drugs (especially antiviral and anticancer ones) with DNA bases such as adenine and guanine is a key factor to explain their effectiveness. Apart from these, it is also found in the structures of substances with antituberculosis, antibacterial, antifungal, anti-inflammatory, and antimalarial activities. Another advantage of this group of compounds is their positive contribution to solubility, polarity, lipophilicity, and hydrogen bonding capacity properties of the compounds they are incorporated into. In this chapter, various bioactivities of fused pyridine derivatives will be categorized and summarized.

Keywords

  • fused pyridine
  • medicinal chemistry
  • furopyridines
  • thiazolopyridine
  • triazolopyridine
  • oxadiazolopyridine

1. Introduction

Fused pyridine heterocyclic ring derivatives are frequently used structures in drug research. Due to the vastness of the chemical space of fused pyridine derivatives, the most common fused pyridine derivatives, namely furopyridines, thienopyridines, pyrrolopyridines, oxazolopyridines, isoxazolopyridines, oxadiazolopyridines, imidazopyridines, pyrazolopyridines, thiazolopyridines, isothiazolopyridines, triazolopyridines, thiadiazolopyridines, tetrazolopyridines, selenazolopyridines, and dithiolopyridines, with their bioactivities were selected to cover in this chapter.

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2. Fused pyridine derivatives

2.1 Furopyridines

Furopyridine synthesis was firstly reported almost a century ago. Since furopyridines are isosteres of benzofuran and indole cores, they are frequently encountered in the chemical structure of compounds possessing various bioactivities such as antihypertensive and antimicrobial.

One of the first studies on furopyridine derivatives focused on anti-inflammatory, anti-aggregation, and anticoagulant activities [1, 2]. Sato et al. reported tetrahydrofuro[3,4-b]pyridine derivatives with coronary vasodilating activity [3]. Garay et al. examined the effect of furopyridines on the stimulation of K+ movement across human red cells membrane [4].

On the other hand, cicletanine, a diuretic drug bearing furopyridine scaffold, used in the treatment of hypertension, also is a competitive histamine antagonist (Figure 1) [5, 6]. Clinical trial on its usage in hypertension with diabetes is ongoing (NCT02709031).

Figure 1.

Furopyridine isomeric structures and example drug molecule bearing furopyridine ring.

In addition to the activities mentioned before, there are several studies on furopyridine containing compounds with antimicrobial, anti-infective, and antiproliferative activities [7, 8, 9, 10, 11, 12, 13, 14]. Also, furopyridine scaffold is present in a HIV protease inhibitor, L-754394 [15, 16]. Interestingly, it is also found in the structure of the antibiotic isolated from the fungus, Cladobotryum varium [17].

Compounds bearing furopyridine scaffold were reported in many studies as both core structure and substituent with kinase inhibitor properties, namely selective inhibitors of cdc-like kinases (CLKs), cyclin-dependent kinase (CDK2) inhibitors, and dk1, cdk2, Fyn, JNK3 kinase inhibitors [18, 19, 20, 21].

On the other hand, furopyridine derivatives were reported possessing melanin-concentrating hormone (MCH1) receptor modulator activity and melatoninergic MT1 and MT2 receptor activity [22, 23].

In addition to these, inhibitor effect against angiogenetic targets on VEGFR2, Tie-2, and EphB4, mGluR5 noncompetitive antagonist activity, cannabinoid-1 receptor inverse agonist activity, σ receptor affinity, 5-HT1A agonists/5-HT3 antagonist activity, and 5-HT1F receptor agonist activity of various compounds bearing furopyridine fused ring were also reported [24, 25, 26, 27, 28, 29].

2.2 Thienopyridines

The first report on bioactivity of thieno[3,2-b]pyridines focused on chemotherapy of parasites (Entamoeba histolytica) [30].

Thienopyridine ring system is an important structural element of anti-aggregation drugs (Figure 2). Ticlopidine, tetrahydrothieno[3,2-c]pyridine derivative, is the first reported drug with in vitro anti-inflammatory (carrageenan-induced edema) and inhibition of ADP-induced platelet aggregation activity in 1974 [2]. Then clopidogrel, having the same ring was reported in 1987 and is still on the market for antiplatelet therapy [31]. Third drug of this class, prasugrel, was reported to the literature in 2000 [32]. Lastly, vicagrel was reported in 2011 to literature and is still undergoing clinical trials (NCT05162053) (Figure 2) [33].

Figure 2.

Thienopyridine isomeric structures and example drug molecules bearing thienopyridine ring.

On the other hand, compounds containing thienopyridine ring were reported having antimicrobial, anti-infective, antiviral, and antiproliferative effects [34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45].

Also, thienopyrimidine ring occurs either as core scaffold or a substituent in a group of kinase inhibitors such as VEGFR, EGFR, Src, Aurora, KDR, B-Raf, Pim kinases, check point 1 kinase (CHK1) IκB kinase-β (IKKβ), COT, and JAK2 inhibitors [46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56].

In addition to these, thienopyridine bearing structures are also associated with HMG-CoA reductase inhibitors, agonists for the luteinizing hormone receptor, histone lysine demethylase KDM5A Inhibitors, ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors, alkaline phosphatase (ALPase) activity, 5-HT1A agonists/5-HT3 antagonists, allosteric modulators of metabotropic Glu5 (mGlu5) and mGlu2 receptors, urotensin-II receptor antagonists, positive allosteric modulator targeting the M4 muscarinic acetylcholine receptor (M4 mAChR), selective inhibitors of Plasmodium falciparum glycogen synthase-3 (PfGSK-3), urea transporter inhibitors, and uridine diphosphate-galactose glycosyltransferase 8 (UGT8) inhibitor in the literature [28, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69].

2.3 Pyrrolopyridines

There are six isomeric structures of pyrrolopyridine ring, and azaindole term is also commonly used in the literature.

First reported bioactivity of pyrrolopyridine-bearing compound had been synthesized by Hooper et al. and had pyrrolo[3,2-b]pyridine scaffold with moderate antibacterial effect [70].

The first pyrrolo[2,3-b]pyridine-derived drug in literature is vemurafenib, a B-Raf enzyme inhibitor for the treatment of melanoma [71, 72]. On the other hand, ceralasertib, a pyrrolo[2,3-b]pyridine-bearing compound, is under phase II trials as ATR kinase inhibitor for antineoplastic therapy (NCT04417062) (Figure 3) [73].

Figure 3.

Pyrrolopyridine isomeric structures and example drug molecules bearing pyrrolopyridine ring.

On the other hand, several studies were reported on pyrrolopyridine ring-derived compounds with antimicrobial, anti-infective, and antiviral activities [74, 75, 76, 77, 78, 79].

Da Settimo et al. reported that pyrrolo[3,4-c]pyridine derivatives with local anesthetic activity and aldose reductase inhibitory properties [80].

Additionally, Kulagowski et al. found out that pyrrolo[2,3-b]pyridine derivatives showed selective D4 receptor antagonist activity [81].

As mentioned before, similar to thienopyridine ring, platelet aggregation inhibitor activity of pyrrolo[3,2-c]pyridine-derived scaffold was reported by Altomare et al. [82].

Moreover, antiproliferative activity of several pyrrolopyridine derivatives was investigated in many studies [83, 84, 85, 86, 87, 88, 89, 90, 91].

Apart from these, compounds bearing pyrrolopyridine moiety were found in various kinase inhibitors such as Met, insulin-like growth factor-1 receptor (IGF-1R), tyrosine, Aurora, Fes and Flt3 tyrosine kinases, Traf2 and Nck-interacting kinase (TNIK), Tau Tubulin Kinase 1 (TTBK1), JAK1 selective, BTK, DYRK1A, and RAF-1 dual inhibitor [92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103].

Lastly, many compounds containing fused pyrrolopyridine anologs were reported in the literature having several different bioactivities such as allosteric mGluR5 antagonist activity, diacylglycerol acyltransferase-2 inhibitors, antagonists of the G-protein-coupled chemoattractant receptor (CRTh2), in vivo TNF-a inhibitory activity, preventing protein phosphatase 2A (PP2A) inhibition, human neutrophil elastase (HNE) inhibitors, retinoic acid receptor-related orphan C2 (RORC2) inverse agonist, selective GluN2B negative allosteric modulators, 5-HT1F receptor agonist, agonist of ORL-1(Opioid receptor-like) receptor, and cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor agonist activity [104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116].

2.4 Oxazolopyridines, isoxazolopyridines, and oxadiazolopyridines

Oxazolopyridine derivatives, an aza analog of benzoxazole, have been studied extensively since the first report of their synthesis by Fraser and Tittensor in 1956 (Figure 4) [117]. Yet, the first bioactivity (anthelmintic and acaricidal activity) of compounds with oxazolopyridine moiety, namely oxazolo[4,5-b]pyridine, was reported nearly 20 years later by Rüfenacht et al., and then, oxazolo[5,4-b]pyridine-bearing compounds were reported having carrageenan rat foot edema assay activity by Clark et al. [118, 119]. Later, antimicrobial, anti-infective, antiviral, and antiproliferative activities of several compounds having oxazololopyridine moiety were reported [120, 121, 122, 123, 124].

Figure 4.

Oxazolopyridine, isoxazolopyridine, and oxadiazolopyridine isomeric structures.

Additionally, various bioactivities such as fatty acid amide hydrolase (FAAH), topoisomerase II, monoamine oxidase B, GSK-3beta-, sphingomyelin synthase 2 inhibitory, SIRT1 activation, and histamine H3-receptor antagonistic activity of oxazololopyridine moiety-bearing compounds were reported in the literature [125, 126, 127, 128, 129, 130, 131, 132, 133].

Although the synthesis of isoxazolo[5,4-b]pyridines was reported in 1968 by Markillie, there has been a few bioactivity studies on isoxazolopyridine derivatives including GABAergic activity, HMG-CoA reductase inhibitory activity, anticancer activity, polo-like kinase inhibitor activity, and gamma-secretase modulator activity (Figure 4) [57, 134, 135, 136, 137, 138].

The synthesis of oxadiazolopyridine core was firstly reported by Bailey et al. in 1971 (Figure 4) [139]. Only antitumor activity and fluorescent properties of oxadiazolopyridine containing compounds were reported [140, 141].

2.5 Imidazopyridines

Imidazo[4,5-b]pyridine, the first synthesized imidazopyridine isomer, was synthesized by Takahashi and Yajima in 1946, and then analeptic activity of imidazopyridine was reported in 1965 [142, 143].

Imidazopyridines are one of the most studied fused pyridine ring systems; therefore, it is found in many drugs’ structures (Figure 5). The various bioactivity profiles of these groups of compounds might be associated with the fact that imidazopyridines, also known as 3-deazapurines, are isosteres of purine ring.

Figure 5.

Imidazopyridine isomeric structures and example drug molecules bearing imidazopyridine ring.

Miroprofen, an imidazo[1,2-a]pyridine derived NSAID, has analgesic, antipyretic, and anti-inflammatory activity. Another imidazo[1,2-a]pyridine derivative, Zolpidem, is a hypnotic drug and positive GABA-A receptor modulator. Similarly, Alpidem, Necopidem, and Saripidem are other imidazo[1,2-a]pyridine containing anxiolytic drugs. Olprinone acts as a cardiotonic agent and is used in Japan. Zolimidine is a marketed anti-ulcerative drug. Minodronic acid, a bone resorption inhibitor and Sch 28080, gastric antisecretic compound, and H+K+-ATPase inhibitior are other imidazo[1,2-a]pyridine-bearing compounds [144, 145, 146, 147, 148, 149, 150, 151, 152].

Imidazo[4,5-b]pyridine ring is occurred in various drugs including Vardax (sulmazole), a cardiotonic drug with positive inotropic activity, phosphodiesterase inhibition and adenosine receptor antagonist activity, and Rimegepant and Telcagepant, antimigraine drugs possessing CGRP receptor antagonists activity. Additionally, imidazo[4,5-b]pyridine-derived Tenatoprazole is reported with proton pump inhibitory activity and gastric acid secretion inhibitory properties in rats [153, 154, 155, 156, 157, 158].

On the other hand, Tegobuvir, imidazo[4,5-c]pyridine-bearing compound, is used in prophylaxis and treatment of HCV infection, and Fadrozole, a Tetrahydroimidazo[1,5-a]pyridine derivative, is a nonsteroidal aromatase inhibitor for breast cancer treatment [159, 160, 161, 162].

Moreover, there are several reports on imidazopyridine-bearing compounds possessing antibacterial, antiviral (HIV, etc.), and antiparasitic (anti-leishmanial and anti-trypanosomal) properties [163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174]. Also, imidazopyridine derivatives are often studied as anticancer agents [175, 176, 177, 178, 179, 180, 181].

The imidazopyridine scaffold has been reported in the structures of various kinase inhibitors, such as KDR kinase, calmodulin-dependent kinase II (CaMKII), Glycogen Synthase Kinase-3, cyclin-dependent kinase (CDK), Bruton’s tyrosine kinase, AKT Kinase, c-Met kinase, VEGFR2 kinase, FLT3 kinase, Pan-JAK, Aurora-A kinase, phosphatidylinositol-3-kinase (PI3K) and apoptosis signal-regulating kinase 1 (ASK1) [182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195].

In addition to these bioactivities, imidazopyridine ring isomers expressed several including positive modulation of GABA-A receptor, positive allosteric modulation of metabotropic glutamate receptor 2 (mGluR2), angiotensin II receptor antagonist, receptor-related orphan receptor gamma (RORc) inverse agonist, melanin-concentrating hormone receptor 1 (MCHR1) antagonist, anti-inflammatory, anticonvulsant, phosphodiesterase (PDE) inhibitory, platelet-activating factor antagonist, TNF-α suppressing, mammalian target of rapamycin (mTOR) inhibitory, autotaxin inhibitory, cholinesterase inhibitory, and PARP-1 inhibitory activities in the literature [196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209].

2.6 Pyrazolopyridines

The synthesis of pyrazolopyridines was reported firstly by Englert and McElvain (Figure 6) [210]. Shortly after the synthesis, compounds containing pyrazolopyridine moiety with anti-inflammatory, antipyretic, and analgesic activity were reported [211]. Additionally, antibacterial (against both gram-positive and gram-negative bacteria), antiviral (anti-enterovirus), and antifungal and antiparasitic (antimalarial) activity reports of pyrazolopyridine-bearing compounds were reported in the literature [212, 213, 214, 215, 216, 217]. Moreover, anticancer activity of various pyrazolopyridine derivatives was investigated in many studies [218, 219, 220, 221, 222].

Figure 6.

Pyrazolopyridine isomeric structures.

Apart from these, many kinase inhibitors, namely CDK1/CDK2, glycogen synthase kinase-3, protein kinase Cθ (PKCθ), phosphatidylinositol-3-kinases (PI3K), aurora-A kinase, pim-kinase, TYK2, ALK5 (activin receptor-like kinase 5), anaplastic lymphoma kinase (ALK), and mitogen-activated protein kinase kinase 4 (MKK4) inhibitors, have pyrazolopyridine ring in their scaffold [223, 224, 225, 226, 227, 228, 229, 230, 231, 232].

Lastly, in addition to activities mentioned before, anxiolytic, adenosine A1 receptor antagonist, PDE4, PDE5, PDE9 inhibitory, mTOR inhibitory, guanylate cyclase agonist, B-RafV600E inhibitory, dopamine D3 receptor agonist, and tubulin polymerization inhibitory and cholinesterase inhibitory activity of pyrazolopyridine derivatives were reported [233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244].

2.7 Thiazolopyridines and isothiazolopyridines

Thiazolo[4,5-b]pyridine ring was synthesized by Saikachi in 1944 [245]. The first reported bioactivity of thiazolopyridine was antituberculous activity of thiazolo[4,5-c]pyridine derivatives (Figure 7) [246].

Figure 7.

Thiazolopyridine and isothiazolopyridine isomeric structures.

Antibacterial (against both gram-positive and gram-negative bacteria), antiviral, antifungal, antituberculose, and antiparasitic activity of compounds containing thiazolopyridine structure were reported [247, 248, 249, 250, 251]. Additionally, cytotoxic and anticancer activity of thiazolopyridine derivatives were investigated in many studies [252, 253, 254, 255].

Moreover, there are many thiazolopyridine-bearing compounds with various bioactivity profile, such as histamine H3-receptor antagonistic activity, mGluR5—metabotropic glutamate receptor subtype 5-antagonist, sphingosine-1-phosphate (S1P) agonist, DNA Gyrase B (GyrB) ATPase inhibitor, anti-inflammatory activity, phosphoinositide 3-kinase inhibitor, and allosteric inhibitor of MALT1 [129, 256, 257, 258, 259, 260, 261].

On the other hand, synthesis of isothiazolopyridines was firstly reported by Taurins and Khouw in 1997 [262]. Later, in vivo anorectic action activity of isothiazolo[5, 4-b]pyridine derivatives was reported by Malinka and Rutkowska [263]. There have been a few reports on bioactivity of isothiazolopyridine derivatives such as antitumor and radioprotective activities, in vitro antibacterial activity, analgesic activity, cyclin G-associated kinase inhibition, antiviral activity, and COX-1/2 inhibitory activity [264, 265, 266, 267, 268, 269].

2.8 Triazolopyridines

Triazolopyridine scaffold is an isostere of purine ring; therefore, there are several bioactivity reports on compounds containing triazolopyridine ring.

The first report on the synthesis of (3H)1,2,3-triazolo[4,5-c]pyridine derivatives and their analeptic activity was published by Reitmann in 1936 [270].

1,2,3-Triazolo[4,5-b]pyridine and 1,2,3-triazolo[4,5-c]pyridine derivatives were reported possessing depressant, tranquilizing, anticonvulsant, and cardiovascular activities [143].

An antidepressant drug Trazodone, 1,2,4-triazolo[4,3-a]pyridine derivative, was first reported in 1968 and has been used commonly for the treatment of depression (Figure 8) [271]. In addition to its antidepressant effect, it was recently reported that trazodone inhibits tau amyloidogenesis [272].

Figure 8.

Triazolopyridine isomeric structures and example drug molecule-bearing pyrrolopyridine ring.

On the other hand, several triazolopyridine-containing compounds were reported having antibacterial, antiviral, antifungal, antituberculose, and antiparasitic activity [273, 274, 275, 276, 277, 278]. Additionally, triazolopyridine derivatives were investigated in many studies for their anticancer activity [279, 280, 281].

Similar to other fused pyridine derivatives, triazolopyridine scaffold has been reported in many papers as kinase inhibitors, such as PIM kinase, JAK1, JAK2, PI3K-gama-delta, ALK-5, VEGFR2 kinase, spleen tyrosine kinase (Syk), c-met kinase, and monopolar spindle 1 (MPS1) kinase inhibitors [282, 283, 284, 285, 286, 287, 288, 289, 290].

Lastly, compounds containing triazolopyridine ring were evaluated for their bioactivities, such as anti-inflammatory, p38R, 11beta-hydroxysteroid dehydrogenase-type 1 (11beta-HSD-1), prolylhydroxylase domain-1 (PHD-1), myeloperoxidase, tubulin polymerization, polycomb repressive complex 2 (PRC2) inhibitory, HIV-1 allosteric inhibitor activity, mGlu receptor 2 (mGluR2) PAM, muscarinic acetylcholine receptor subtype 1 (M1) PAM, and retinoic acid receptor-related orphan nuclear receptor gama-t (RORγt) inverse agonist [174, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303].

2.9 The other five-membered heteroaromatic ring fused pyridine derivatives

Apart from fused pyridine derivatives mentioned before, there are several reports on five-membered heteroaromatic fused pyridine ring derivatives possessing bioactivity (Figure 9).

Figure 9.

Five-membered heteroaromatic ring fused pyridine derivatives.

For instance, 1,3,4-thiadiazolo[3,2-a]pyridine derivatives were reported having antimicrobial effects [304]. On the other hand, tetrahydrotetrazolopyridine scaffold was found in bovine liver-D-glucuronidase and human-alfa-L-iduronidase inhibitors [305]. Interestingly, an unusual fused pyridine derivative selenazolo[5,4-b]pyridine scaffold can highly induce apoptosis in human breast carcinoma MCF-7 cells [306]. Lastly, dithiolo[4,5-b]pyridine derivatives were reported possessing antimicrobial activity [307].

2.10 Conclusion

In conclusion, fused five-membered pyridine heteroaromatic rings are privileged scaffolds in medicinal chemistry. Therefore, selected ring systems and their bioactivities are covered in this chapter.

There are several drugs containing these heteroaromatic rings on the market, and several phase trials are ongoing on various compounds. Considering the chemical similarity between fused pyridine rings and nucleobases and amino acids, the wide variety of the bioactivity is unsurprising. The most commonly reported bioactivities of these kinds of derivatives are antimicrobial, anticancer, and kinase inhibition.

References

  1. 1. Maffrand JP, Eloy F. Synthesis of thienopyridines and furopyridines of therapeutic interest. European Journal of Medicinal Chemistry. 1974;9(5):483-486
  2. 2. Podesta M, Aubert D, Ferrand JC. Pharmacological study of thienopyridine and furopyridine analogs. European Journal of Medicinal Chemistry. 1974;9(5):487-490
  3. 3. Sato Y, Shimoji Y, Fujita H, Mizuno H, et al. Synthetic studies on cardiovascular agents. IV. Synthesis of fused dihydropyridine derivatives. Yakugaku Zasshi. 1978;98(4):448-465. DOI: 10.1248/yakushi1947.98.4_448
  4. 4. Garay RP, Nazaret C, Diez J, Etienne A, et al. Stimulation of potassium fluxes by diuretic drugs in human red cells. Biochemical Pharmacology. 1984;33(13):2013-2020. DOI: 10.1016/0006-2952(84)90567-7
  5. 5. Schoeffter P, Ghysel-Burton J, Cabanie M, Godfraind T. Competitive and stereoselective histamine H1-antagonistic effect of cicletanide in guinea pig isolated ileum. European Journal of Pharmacology. 1987;136(2):235-237. DOI: 10.1016/0014-2999(87)90716-3
  6. 6. Auguet M, Delaflotte S, Hellegouarch A, Guillon JM, et al. In vitro cardiovascular antihistamine properties of cicletanine in comparison with diphenhydramine. Drugs under Experimental and Clinical Research. 1988;14(2-3):149-153
  7. 7. Salem MS, Sakr SI, El-Senousy WM, Madkour HMF. Synthesis, antibacterial, and antiviral evaluation of new heterocycles containing the pyridine moiety. Archiv der Pharmazie. 2013;346:766-773. DOI: 10.1002/ardp.201300183
  8. 8. Hung JM, Arabshahi HJ, Leung E, Reynisson J, et al. Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives. European Journal of Medicinal Chemistry. 2014;86:420-437. DOI: 10.1016/j.ejmech.2014.09.001
  9. 9. Naresh KR, Poornachandra Y, Nagender P, Mallareddy G, et al. Synthesis of novel trifluoromethyl substituted furo[2,3-b]pyridine and pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine derivatives as potential anticancer agents. European Journal of Medicinal Chemistry. 2016;108:68-78. DOI: 10.1016/j.ejmech.2015.11.007
  10. 10. Parcella K, Eastman K, Yeung K-S, Grant-Young KA, et al. Improving metabolic stability with deuterium: The discovery of BMT-052, a pan-genotypic HCV NS5B polymerase inhibitor. ACS Medicinal Chemistry Letters. 2017;8(7):771-774. DOI: 10.1021/acsmedchemlett.7b00211
  11. 11. Santhosh KG, Poornachandra Y, Kumar GS, Ratnakar RK, et al. Synthesis of novel hetero ring fused pyridine derivatives; their anticancer activity, CoMFA and CoMSIA studies. Bioorganic & Medicinal Chemistry Letters. 2018;28(13):2328-2337. DOI: 10.1016/j.bmcl.2018.04.031
  12. 12. Laxmi DS, Vardhini SV, Guttikonda VR, Rao MVB, et al. Synthesis of 2-substituted furo[3,2-b]pyridines under Pd/C-Cu catalysis assisted by ultrasound: Their evaluation as potential cytotoxic agents. Anti-Cancer Agents in Medicinal Chemistry. 2020;20(8):932-940. DOI: 10.2174/1871520620666200311102304
  13. 13. Said AB, Al-Refai M, Geyer A, Mansi IA, et al. Synthesis, characterization, antibacterial and cytotoxic evaluation of new 6-(chlorothiophenyl)-2-(2-oxopropoxy)pyridine-3-carbonitrile derivatives and their corresponding furo[2,3-b]pyridine derivatives. Heterocycles. 2021;102(11):2153-2167. DOI: 10.3987/com-21-14534
  14. 14. Silva DG, Anna J, de Melo SMG, Fumagalli F, et al. Synthesis and structure-activity relationships of imidazopyridine/pyrimidine- and Furopyridine-based anti-infective agents against trypanosomiases. ChemMedChem. 2021;16(6):966-975. DOI: 10.1002/cmdc.202000616
  15. 15. Houpis IN, Choi WB, Reider PJ, Audrey M, et al. Synthesis of functionalized furo[2,3-b]pyridines via the Pd-catalyzed coupling of acetylenes to iodopyridones. Preparation of a key intermediate to a new HIV protease inhibitor L-754,394. Tetrahedron Letters. 1994;35(50):9355-9358. DOI: 10.1016/s0040-4039(00)78541-8
  16. 16. Huff JR, Vacca JP, Dorsey BD. HIV Protease Inhibitors. WO9516688 A1. 1995
  17. 17. Sakemi S, Jon B, DeCosta DL, Dekker KA, et al. CJ-15,696 and its analogs, new furopyridine antibiotics from the fungus Cladobotryum varium: Fermentation, isolation, structural elucidation, biotransformation and antibacterial activities. Journal of Antibiotics. 2002;55(1):6-18. DOI: 10.7164/antibiotics.55.6
  18. 18. Václav N, Michaela H, Lukáš M, Jana F, et al. Furo[3,2-b]pyridine: A privileged scaffold for highly selective kinase inhibitors and effective modulators of the hedgehog pathway. Angewandte Chemie. 2019;58(4):1062-1066. DOI: 10.1002/anie.201810312
  19. 19. Nemec V, Maier L, Berger B-T, Chaikuad A, et al. Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core. European Journal of Medicinal Chemistry. 2021;215:113299. DOI: 10.1016/j.ejmech.2021.113299
  20. 20. Abdel-Rahman AA-H, Shaban AKF, Nassar IF, EL-Kady DS, et al. Discovery of new pyrazolopyridine, furopyridine, and pyridine derivatives as CDK2 inhibitors: Design, synthesis, docking studies, and anti-proliferative activity. Molecules. 2021;26(13):3923. DOI: 10.3390/molecules26133923
  21. 21. Schade N, Koch P, Ansideri F, Krystof V, et al. Evaluation of novel substituted furopyridines as inhibitors of protein kinases related to tau pathology in Alzheimer’s disease. Medicinal Chemistry (Sharjah, United Arab Emirates). 2021;17(8):844-855. DOI: 10.2174/1573406417666210601144510
  22. 22. Guzzo P, Surman MD. 5-Furopyridinone Substituted Indazoles. WO2008086409. 2008
  23. 23. Couhert A, Delagrange P, Caignard D-H, Chartier A, et al. Synthesis of 2-arylfuro[3,2-b]pyridines: Effect of the C2-aryl group on melatoninergic activity. European Journal of Medicinal Chemistry. 2016;109:268-275. DOI: 10.1016/j.ejmech.2016.01.008
  24. 24. Miyazaki Y, Nakano M, Sato H, Truesdale AT, et al. Design and effective synthesis of novel templates, 3,7-diphenyl-4-amino-thieno and furo-[3,2-c]pyridines as protein kinase inhibitors and in vitro evaluation targeting angiogenetic kinases. Bioorganic & Medicinal Chemistry Letters. 2007;17:250-254. DOI: 10.1016/j.bmcl.2006.09.050
  25. 25. Rodriguez AL, Williams R, Zhou Y, Lindsley SR, et al. Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype. Bioorganic & Medicinal Chemistry Letters. 2009;19:3209-3213. DOI: 10.1016/j.bmcl.2009.04.110
  26. 26. Debenham JS, Madsen-Duggan CB, Toupence RB, Walsh TF, et al. Furo[2,3-b]pyridine-based cannabinoid-1 receptor inverse agonists: Synthesis and biological evaluation. Bioorganic & Medicinal Chemistry Letters. 2010;20(4):1448-1452. DOI: 10.1016/j.bmcl.2009.12.065
  27. 27. Miyata K, Schepmann D, Wuensch B. Synthesis and σ receptor affinity of regioisomeric spirocyclic furopyridines. European Journal of Medicinal Chemistry. 2014;83:709-716. DOI: 10.1016/j.ejmech.2014.06.073
  28. 28. Asagarasu A, Matsui T, Hayashi H, Tamaoki S, et al. Design and synthesis of piperazinylpyridine derivatives as novel 5-HT1A agonists/5-HT3 antagonists for the treatment of irritable bowel syndrome (IBS). Chemical & Pharmaceutical Bulletin. 2009;57(1):34-42. DOI: 10.1248/cpb.57.34
  29. 29. Mathes BM, Hudziak KJ, Schaus JM, Xu Y-C, et al. Substituted furo[3,2-b]pyridines: Novel bioisosteres of 5-HT1F receptor agonists. Bioorganic & Medicinal Chemistry Letters. 2004;14(1):167-170. DOI: 10.1016/j.bmcl.2003.09.091
  30. 30. Taylor DJ, Greenberg J. Experimental chemotherapy of endamoeba histolytica infections in the guinea pig. American Journal of Hygiene: Monographic Series. 1952;56(1):58-70. DOI: 10.1093/oxfordjournals.aje.a119541
  31. 31. Feliste R, Delebassee D, Simon MF, Chap H, et al. Broad spectrum anti-platelet activity of ticlopidine and PCR 4099 involves the suppression of the effects of released ADP. Thrombosis Research. 1987;48(4):403-415. DOI: 10.1016/0049-3848(87)90398-7
  32. 32. Sugidachi A, Asai F, Ogawa T, Inoue T, et al. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. British Journal of Pharmacology. 2000;129(7):1439-1446. DOI: 10.1038/sj.bjp.0703237
  33. 33. Hongbin S, Jiaqi S, Boyu Z, Fang Y, et al. Optical-Activity 2-Hydroxytetrahydrothienopyridine Derivative, Preparation Method and Application Thereof in Pharmacy. CN102120744 A. 2011
  34. 34. Gilis PM, Haemers A, Bollaert W. Synthesis and antibacterial evaluation of 4,7-dihydro-4-oxothieno[2,3-b]pyridine-5-carboxylic acids. European Journal of Medicinal Chemistry. 1978;13(3):265-269
  35. 35. Attaby FA, Elneairy MAA, Elsayed MS. Synthesis and antimicrobial evaluation of new pyridine, thienopyridine and pyridothienopyrazole derivatives. Archives of Pharmacal Research. 1999;22(2):194-201. DOI: 10.1007/bf02976546
  36. 36. Abdel-Rahman AE, Bakhite EA, Al-Taifi EA. Synthesis and antimicrobial testing of some new S-substituted-thiopyridines, thienopyridines, pyridothienopyrimidines and pyridothienotriazines. Die Pharmazie. 2003;58(6):372-377. DOI: 10.1002/chin.200339135
  37. 37. Bernardino AMR, Pinheiro LCS, Rodrigues CR, Loureiro NI, et al. Design, synthesis, SAR, and biological evaluation of new 4-(phenylamino)thieno[2,3-b]pyridine derivatives. Bioorganic & Medicinal Chemistry. 2006;14(16):5765-5770. DOI: 10.1016/j.bmc.2006.03.013
  38. 38. Zeng X-X, Zheng R-L, Zhou T, He H-Y, et al. Novel thienopyridine derivatives as specific anti-hepatocellular carcinoma (HCC) agents: Synthesis, preliminary structure-activity relationships, and in vitro biological evaluation. Bioorganic & Medicinal Chemistry Letters. 2010;20(21):6282-6285. DOI: 10.1016/j.bmcl.2010.08.088
  39. 39. Abreu RMV, Ferreira ICFR, Calhelha RC, Lima RT, et al. Anti-hepatocellular carcinoma activity using human HepG2 cells and hepatotoxicity of 6-substituted methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate derivatives: In vitro evaluation, cell cycle analysis and QSAR studies. European Journal of Medicinal Chemistry. 2011;46(12):5800-5806. DOI: 10.1016/j.ejmech.2011.09.029
  40. 40. Romagnoli R, Baraldi PG, Kimatrai Salvador MPD, Aghazadeh Tabrizi M, et al. Synthesis and biological evaluation of 2-(Alkoxycarbonyl)-3-Anilinobenzo[b]thiophenes and Thieno[2,3-b]pyridines as new potent anticancer agents. Journal of Medicinal Chemistry. 2013;56(6):2606-2618. DOI: 10.1021/jm400043d
  41. 41. Nakamura RL, Burlingame MA, Yang S, Crosby DC, et al. Identification and optimization of thienopyridine carboxamides as inhibitors of HIV regulatory complexes. Antimicrobial Agents and Chemotherapy. 2017;61(7):e02366-16/1-e02366-16/14. DOI: 10.1128/aac.02366-16
  42. 42. El-Deen EMM, El-Meguid EAA, Hasabelnaby S, Karam EA, et al. Synthesis, docking studies, and in vitro evaluation of some novel thienopyridines and fused thienopyridine-quinolines as antibacterial agents and DNA gyrase inhibitors. Molecules. 2019;24(20):3650. DOI: 10.3390/molecules24203650
  43. 43. Sanad SMH, Mekky AEM. Novel nicotinonitriles and thieno[2,3-b]pyridines as potent biofilm and COX-2 inhibitors: Synthesis, in vitro and in silico studies. ChemistrySelect. 2020;5(28):8494-8503. DOI: 10.1002/slct.202001208
  44. 44. Mugengana AK, Vita NA, Brown GA, Moran K, et al. The discovery and development of thienopyrimidines as inhibitors of helicobacter pylori that act through inhibition of the respiratory complex I. ACS Infectious Diseases. 2021;7(5):1044-1058. DOI: 10.1021/acsinfecdis.0c00300
  45. 45. Elnaggar DH, Mohamed AM, Abdel Hafez NA, Azab ME, et al. Antiproliferative activity of some newly synthesized substituted nicotinamides candidates using pyridine-2(1H) thione derivatives as synthon. ACS Omega. 2022;7(12):10304-10316. DOI: 10.1021/acsomega.1c06951
  46. 46. Munchhof MJ, Beebe JS, Casavant JM, Cooper BA, et al. Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2 kinase activity. Bioorganic & Medicinal Chemistry Letters. 2004;14:21-24. DOI: 10.1016/j.bmcl.2003.10.030
  47. 47. Boschelli DH, Wu B, Sosa ACB, Durutlic H, et al. Synthesis and Src kinase inhibitory activity of 2-phenyl- and 2-thienyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles. Journal of Medicinal Chemistry. 2005;48(11):3891-3902. DOI: 10.1021/jm050175p
  48. 48. Pevet I, Brule C, Tizot A, Gohier A, et al. Synthesis and pharmacological evaluation of thieno[2,3-b]pyridine derivatives as novel c-Src inhibitors. Bioorganic & Medicinal Chemistry. 2011;19(8):2517-2528. DOI: 10.1016/j.bmc.2011.03.021
  49. 49. Curtin ML, Frey RR, Heyman HR, Soni NB, et al. Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families. Bioorganic & Medicinal Chemistry Letters. 2012;22(9):3208-3212. DOI: 10.1016/j.bmcl.2012.03.035
  50. 50. Morwick T, Berry A, Brickwood J, Cardozo M, et al. Evolution of the thienopyridine class of inhibitors of IκB kinase-β: Part I: Hit-to-lead strategies. Journal of Medicinal Chemistry. 2006;49(10):2898-2908. DOI: 10.1021/jm0510979
  51. 51. Heyman HR, Frey RR, Bousquet PF, Cunha GA, et al. Thienopyridine urea inhibitors of KDR kinase. Bioorganic & Medicinal Chemistry Letters. 2007;17(5):1246-1249. DOI: 10.1016/j.bmcl.2006.12.015
  52. 52. Cusack K, Allen H, Bischoff A, Clabbers A, et al. Identification of a selective thieno[2,3-c]pyridine inhibitor of COT kinase and TNF-α production. Bioorganic & Medicinal Chemistry Letters. 2009;19(6):1722-1725. DOI: 10.1016/j.bmcl.2009.01.088
  53. 53. Gopalsamy A, Shi M, Hu Y, Lee F, et al. B-Raf kinase inhibitors: Hit enrichment through scaffold hopping. Bioorganic & Medicinal Chemistry Letters. 2010;20(8):2431-2434. DOI: 10.1016/j.bmcl.2010.03.030
  54. 54. Yang B, Vasbinder MM, Hird AW, Su Q , et al. Adventures in scaffold morphing: Discovery of fused ring heterocyclic checkpoint kinase 1 (CHK1) inhibitors. Journal of Medicinal Chemistry. 2018;61(3):1061-1073. DOI: 10.1021/acs.jmedchem.7b01490
  55. 55. Schenkel LB, Huang X, Cheng A, Deak HL, et al. Discovery of potent and highly selective thienopyridine Janus kinase 2 inhibitors. Journal of Medicinal Chemistry. 2011;54(24):8440-8450. DOI: 10.1021/jm200911r
  56. 56. Naguib BH, El-Nassan HB. Synthesis of new thieno[2,3-b]pyridine derivatives as pim-1 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2016;31(6):1718-1725. DOI: 10.3109/14756366.2016.1158711
  57. 57. Suzuki M, Iwasaki H, Fujikawa Y, Sakashita M, et al. Synthesis and biological evaluations of condensed pyridine and condensed pyrimidine-based HMG-CoA reductase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2001;11:1285-1288. DOI: 10.1016/s0960-894x(01)00203-7
  58. 58. Sasaki S, Cho N, Nara Y, Harada M, et al. Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: A highly potent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptor. Journal of Medicinal Chemistry. 2003;46(1):113-124. DOI: 10.1021/jm020180i
  59. 59. Horton JR, Woodcock CB, Chen Q , Liu X, et al. Structure-based engineering of irreversible inhibitors against histone lysine demethylase KDM5A. Journal of Medicinal Chemistry. 2018;61(23):10588-10601. DOI: 10.1021/acs.jmedchem.8b01219
  60. 60. Mermerian AH, Case A, Stein RL, Cuny GD. Structure-activity relationship, kinetic mechanism, and selectivity for a new class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors. Bioorganic & Medicinal Chemistry Letters. 2007;17(13):3729-3732. DOI: 10.1016/j.bmcl.2007.04.027
  61. 61. Saito K, Nakao A, Shinozuka T, Shimada K, et al. Discovery and structure-activity relationship of thienopyridine derivatives as bone anabolic agents. Bioorganic & Medicinal Chemistry. 2013;21(7):1628-1642. DOI: 10.1016/j.bmc.2013.01.071
  62. 62. Nogradi K, Wagner G, Domany G, Bobok A, et al. Thieno[2,3-b]pyridines as negative allosteric modulators of metabotropic GluR5 receptors: Hit-to-lead optimization. Bioorganic & Medicinal Chemistry Letters. 2014;24(16):3845-3849. DOI: 10.1016/j.bmcl.2014.06.057
  63. 63. Childress ES, Wieting JM, Felts AS, Breiner MM, et al. Discovery of novel central nervous system penetrant metabotropic glutamate receptor subtype 2 (mGlu2) negative allosteric modulators (NAMs) based on functionalized pyrazolo[1,5-a]pyrimidine-5-carboxamide and thieno[3,2-b]pyridine-5-carboxamide cores. Journal of Medicinal Chemistry. 2019;62(1):378-384. DOI: 10.1021/acs.jmedchem.8b01266
  64. 64. Barbaro L, Rodriguez AL, Blevins AN, Dickerson JW, et al. Discovery of “molecular switches” within a series of mglu5 allosteric ligands driven by a “magic methyl” effect affording both PAMs and NAMs with in vivo activity, derived from an M1 PAM chemotype. ACS Biological and Medicinal Chemistry AU. 2021;1(1):21-30. DOI: 10.1021/acsbiomedchemau.1c00024
  65. 65. Lim CJ, Oh SA, Lee BH, Oh K-S, et al. Synthesis and SAR of thieno[3,2-b]pyridinyl urea derivatives as urotensin-II receptor antagonists. Bioorganic & Medicinal Chemistry Letters. 2014;24(24):5832-5835. DOI: 10.1016/j.bmcl.2014.09.089
  66. 66. Huynh T, Valant C, Crosby IT, Sexton PM, et al. Synthesis and pharmacological evaluation of M4 muscarinic receptor positive allosteric modulators derived from VU10004. ACS Chemical Neuroscience. 2015;6(6):838-844. DOI: 10.1021/acschemneuro.5b00035
  67. 67. Masch A, Nasereddin A, Alder A, Bird MJ, et al. Structure-activity relationships in a series of antiplasmodial thieno[2,3-b]pyridines. Malaria Journal. 2019;18(1):89. DOI: 10.1186/s12936-019-2725-y
  68. 68. Zhao Y, Li M, Li B, Zhang S, et al. Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors. European Journal of Medicinal Chemistry. 2019;172:131-142. DOI: 10.1016/j.ejmech.2019.03.060
  69. 69. Zaccariotto E, Cachon-Gonzalez MB, Wang B, Lim S, et al. A novel brain-penetrant oral UGT8 inhibitor decreases in vivo galactosphingolipid biosynthesis in murine Krabbe disease. Biomedicine & Pharmacotherapy. 2022;149:112808. DOI: 10.1016/j.biopha.2022.112808
  70. 70. Hooper M, Patterson DA, Wibberley DG. Preparation and antibacterial activity of isatogens and related compounds. Journal of Pharmacy and Pharmacology. 1965;17(11):734-741. DOI: 10.1111/j.2042-7158.1965.tb07596.x
  71. 71. Ibrahim P, Artis D, Bremer R, Mamo S, et al. Pyrrolo[2,3-b] Pyridine Derivatives as Protein Kinase Inhibitors. WO2007002325A1. 2007
  72. 72. Aziz N, Moler E, Stuart D, Heise C, et al. Biomarkers of Target Modulation, Efficacy, Diagnosis and/or Prognosis for RAF Inhibitors. WO2008082730A2. 2008
  73. 73. Foote KM, Nissink JWM, Turner P. Morpholino Pyrimidines and Their Use in Therapy. WO2011154737 A1. 2011
  74. 74. Toja E, Tarzia G, Ferrari P, Tuan G. Pyrrolopyridine analogs of nalidixic acid. 1. Pyrrolo[2,3-b]pyridines. Journal of Heterocyclic Chemistry. 1986;23(5):1555-1560. DOI: 10.1002/jhet.5570230560
  75. 75. Minakata S, Itoh S, Komatsu M, Ohshiro Y. Functionalization of 1H-pyrrolo[2,3-b]pyridine. Bulletin of the Chemical Society of Japan. 1992;65(11):2992-2997. DOI: 10.1246/bcsj.65.2992
  76. 76. Paget SD, Boggs CM, Foleno BD, Goldschmidt RM, et al. Antibacterial activity of pyrrolopyridine-substituted oxazolidinones: Synthesis and in vitro SAR of various C-5 acetamide replacements. Bioorganic & Medicinal Chemistry Letters. 2006;16(17):4537-4542. DOI: 10.1016/j.bmcl.2006.06.023
  77. 77. Khoje AD, Charnock C, Wan B, Franzblau S, et al. Synthesis and antimycobacterial activities of non-purine analogs of 6-aryl-9-benzylpurines: Imidazopyridines, pyrrolopyridines, benzimidazoles, and indoles. Bioorganic & Medicinal Chemistry. 2011;19(11):3483-3491. DOI: 10.1016/j.bmc.2011.04.023
  78. 78. Jose G, Suresha Kumara TH, Sowmya HBV, Sriram D, et al. European Journal of Medicinal Chemistry. Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine Mannich bases. 2017;131:275-288. DOI: 10.1016/j.ejmech.2017.03.015
  79. 79. Saigal D, Ghanem YSA, Uddin A, Khan S, et al. Synthesis, biological evaluation and docking studies of functionalized Pyrrolo[3,4-b]pyridine derivatives. ChemistrySelect. 2021;6(9):2323-2334. DOI: 10.1002/slct.202004781
  80. 80. Da Settimo A, Primofiore G, Da Settimo F, Simorini F, et al. Synthesis of pyrrolo[3,4-c]pyridine derivatives possessing an acid group and their in vitro and in vivo evaluation as aldose reductase inhibitors. European Journal of Medicinal Chemistry. 1996;31:49-58. DOI: 10.1016/s0223-5234(96)80006-7
  81. 81. Kulagowski JJ, Broughton HB, Curtis NR, Mawer IM, et al. 3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine: An antagonist with high affinity and selectivity for the human dopamine D4 receptor. Journal of Medicinal Chemistry. 1996;39(10):1941-1942. DOI: 10.1021/jm9600712
  82. 82. Altomare C, Summo L, Cellamare S, Varlamov AV, et al. Pyrrolo[3,2-c]pyridine derivatives as inhibitors of platelet aggregation. Bioorganic & Medicinal Chemistry Letters. 2000;10:581-584. DOI: 10.1016/s0960-894x(00)00052-4
  83. 83. Guillard J, Decrop M, Gallay N, Espanel C, et al. Synthesis and biological evaluation of 7-azaindole derivatives, synthetic cytokinin analogues. Bioorganic & Medicinal Chemistry Letters. 2007;17:1934-1937. DOI: 10.1016/j.bmcl.2007.01.033
  84. 84. Kim HJ, Jung M-H, Kim H, El-Gamal MI, et al. Synthesis and antiproliferative activity of pyrrolo[3,2-b]pyridine derivatives against melanoma. Bioorganic & Medicinal Chemistry Letters. 2010;20(1):413-417. DOI: 10.1016/j.bmcl.2009.08.005
  85. 85. El-Gamal MI, Jung M-H, Lee WS, Sim T, et al. Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. European Journal of Medicinal Chemistry. 2011;46(8):3218-3226
  86. 86. Jung M-H, El-Gamal MI, Abdel-Maksoud MS, Sim T, et al. Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. Part 2. Bioorganic & Medicinal Chemistry Letters. 2012;22(13):4362-4367. DOI: 10.1016/j.bmcl.2012.05.004
  87. 87. Carbone A, Parrino B, Di Vita G, Attanzio A, et al. Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogues. Marine Drugs. 2015;13(1):460-492. DOI: 10.3390/md13010460
  88. 88. Narva S, Chitti S, Bala BR, Alvala M, et al. Synthesis and biological evaluation of pyrrolo[2,3-b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA. European Journal of Medicinal Chemistry. 2016;114:220-231. DOI: 10.1016/j.ejmech.2016.02.059
  89. 89. Tang Q , Duan Y, Wang L, Wang M, et al. Synthesis and antiproliferative activity of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety. European Journal of Medicinal Chemistry. 2018;143:266-275. DOI: 10.1016/j.ejmech.2017.11.034
  90. 90. Ullah S, El-Gamal MI, El-Gamal R, Pelletier J, et al. Synthesis, biological evaluation, and docking studies of novel pyrrolo[2,3-b]pyridine derivatives as both ectonucleotide pyrophosphatase/phosphodiesterase inhibitors and antiproliferative agents. European Journal of Medicinal Chemistry. 2021;217:113339. DOI: 10.1016/j.ejmech.2021.113339
  91. 91. Zhang J, Dai J, Lan X, Zhao Y, et al. Synthesis, bioevaluation and molecular dynamics of pyrrolo-pyridine carboxamide derivatives as potential antitumor agents in vitro and in vivo. European Journal of Medicinal Chemistry. 2022;233:114215. DOI: 10.1016/j.ejmech.2022.114215
  92. 92. Pin F, Buron F, Saab F, Colliandre L, et al. Synthesis and biological evaluation of 2,3-bis(het)aryl-4-azaindole derivatives as protein kinase inhibitors. MedChemComm. 2011;2(9):899-903. DOI: 10.1039/C1MD00141H
  93. 93. Cai Z-W, Wei D, Schroeder GM, Cornelius LAM, et al. Discovery of orally active pyrrolopyridine- and aminopyridine-based met kinase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2008;18(11):3224-3229. DOI: 10.1016/j.bmcl.2008.04.047
  94. 94. Kim KS, Zhang L, Schmidt R, Cai Z-W, et al. Discovery of pyrrolopyridine-pyridone based inhibitors of met kinase: Synthesis, X-ray crystallographic analysis, and biological activities. Journal of Medicinal Chemistry. 2008;51(17):5330-5341. DOI: 10.1021/jm800476q
  95. 95. Wang W, Xu S, Duan Y, Liu X, et al. Synthesis and bioevaluation and docking study of 1H-pyrrolo[2,3-b]pyridine derivatives bearing aromatic hydrazone moiety as c-Met inhibitors. European Journal of Medicinal Chemistry. 2018;145:315-327. DOI: 10.1016/j.ejmech.2017.12.078
  96. 96. Patnaik S, Stevens KL, Gerding R, Deanda F, et al. Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase. Bioorganic & Medicinal Chemistry Letters. 2009;19(11):3136-3140. DOI: 10.1016/j.bmcl.2008.12.110
  97. 97. Song P, Chen M, Ma X, Xu L, et al. Identification of novel inhibitors of Aurora A with a 3-(pyrrolopyridin-2-yl)indazole scaffold. Bioorganic & Medicinal Chemistry. 2015;23(8):1858-1868. DOI: 10.1016/j.bmc.2015.02.004
  98. 98. Park E, Lee SJ, Moon H, Park J, et al. Discovery and biological evaluation of N-methyl-pyrrolo[2,3-b]pyridine-5-carboxamide derivatives as JAK1-selective inhibitors. Journal of Medicinal Chemistry. 2021;64(2):958-979. DOI: 10.1021/acs.jmedchem.0c01026
  99. 99. Weir MC, Hellwig S, Tan L, Yao L, et al. Dual inhibition of Fes and flt3 tyrosine kinases potently inhibits flt3-itd+ aml cell growth. PLoS One. 2017;12(7):e0181178/1-e0181178/19. DOI: 10.1371/journal.pone.0181178
  100. 100. Thakkar M, Bhuniya D, Kaduskar R, Mengawade T, et al. Discovery and evaluation of 1H-pyrrolo[2,3-b]pyridine based selective and reversible small molecule BTK inhibitors for the treatment of rheumatoid arthritis. Bioorganic & Medicinal Chemistry Letters. 2017;27(8):1867-1873. DOI: 10.1016/j.bmcl.2017.02.026
  101. 101. Halkina T, Henderson JL, Lin EY, Himmelbauer MK, et al. Discovery of potent and brain-penetrant tau tubulin kinase 1 (TTBK1) inhibitors that lower tau phosphorylation in vivo. Journal of Medicinal Chemistry. 2021;64(9):6358-6380. DOI: 10.1021/acs.jmedchem.1c00382
  102. 102. Kircher T, Pantsar T, Oder A, Peter von Kries J, et al. Design and synthesis of novel fluorescently labeled analogs of vemurafenib targeting MKK4. European Journal of Medicinal Chemistry. 2021;209:112901. DOI: 10.1016/j.ejmech.2020.112901
  103. 103. Yang B, Wu Q , Huan X, Wang Y, et al. Discovery of a series of 1H-pyrrolo[2,3-b]pyridine compounds as potent TNIK inhibitors. Bioorganic & Medicinal Chemistry Letters. 2021;33:127749. DOI: 10.1016/j.bmcl.2020.127749
  104. 104. Koller M, Carcache DA, Orain D, Ertl P, et al. Discovery of 1H-pyrrolo[2,3-c]pyridine-7-carboxamides as novel, allosteric mGluR5 antagonists. Bioorganic & Medicinal Chemistry Letters. 2012;22(20):6454-6459. DOI: 10.1016/j.bmcl.2012.08.053
  105. 105. Kim MO, Lee S, Choi K, Lee S, et al. Discovery of a novel class of diacylglycerol acyltransferase 2 inhibitors with a 1H-pyrrolo[2,3-b]pyridine core. Biological & Pharmaceutical Bulletin. 2014;37(10):1655-1660. DOI: 10.1248/bpb.b14-00447
  106. 106. Bala K, Leblanc C, Sandham DA, Turner KL, et al. Organic Compounds. WO2005123731 A2. 2005
  107. 107. Hilmy KMH, Abdul-Wahab HG, Soliman DH, Khalifa MMA, et al. Novel pyrrolo[2,3-d]pyrimidines and pyrrolo[2,3-b]pyridines: Design, synthesis, and in vivo TNF-α inhibitory activity. Medicinal Chemistry Research. 2015;25(4):2097-2110. DOI: 10.1007/s00044-014-1281-9
  108. 108. Lajarin-Cuesta R, Arribas RL, Nanclares C, Garcia-Frutos EM, et al. Design and synthesis of multipotent 3-aminomethylindoles and 7-azaindoles with enhanced protein phosphatase 2A-activating profile and neuroprotection. European Journal of Medicinal Chemistry. 2018;157:294-309. DOI: 10.1016/j.ejmech.2018.07.030
  109. 109. Crocetti L, Giovannoni MP, Schepetkin IA, Quinn MT, et al. 1H-pyrrolo[2,3-b]pyridine: A new scaffold for human neutrophil elastase (HNE) inhibitors. Bioorganic & Medicinal Chemistry. 2018;26(21):5583-5595. DOI: 10.1016/j.bmc.2018.09.034
  110. 110. Cantini N, Khlebnikov AI, Crocetti L, Schepetkin IA, et al. Exploration of nitrogen heterocycle scaffolds for the development of potent human neutrophil elastase inhibitors. Bioorganic & Medicinal Chemistry. 2021;29:115836. DOI: 10.1016/j.bmc.2020.115836
  111. 111. Schnute ME, Wennerstal M, Alley J, Bengtsson M, et al. Discovery of 3-cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide: A potent, selective, and orally bioavailable retinoic acid receptor-related orphan receptor C2 inverse agonist. Journal of Medicinal Chemistry. 2018;61(23):10415-10439. DOI: 10.1021/acs.jmedchem.8b00392
  112. 112. Chrovian CC, Soyode-Johnson A, Wall JL, Rech JC, et al. 1H-Pyrrolo[3,2-b]pyridine GluN2B-selective negative allosteric modulators. ACS Medicinal Chemistry Letters. 2019;10(3):261-266. DOI: 10.1021/acsmedchemlett.8b00542
  113. 113. Filla SA, Mathes BM, Johnson KW, Phebus LA, et al. Novel potent 5-HT1F receptor agonists: Structure-activity studies of a series of substituted N-[3-(1-methyl-4-piperidinyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]amides. Journal of Medicinal Chemistry. 2003;46(14):3060-3071. DOI: 10.1021/jm030020m
  114. 114. Bignan GC, Battista K, Connolly PJ, Orsini MJ, et al. 3-(4-piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo[2,3-b]pyridines as ligands for the ORL-1 receptor. Bioorganic & Medicinal Chemistry Letters. 2006;16(13):3524-3528. DOI: 10.1016/j.bmcl.2006.03.094
  115. 115. Blaazer AR, Lange JHM, van der Neut MAW, Mulder A, et al. Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists: Design, synthesis, structure-activity relationships, physicochemical properties and biological activity. European Journal of Medicinal Chemistry. 2011;46(10):5086-5098. DOI: 10.1016/j.ejmech.2011.08.021
  116. 116. Sparkes E, Cairns EA, Kevin RC, Lai F, et al. Structure-activity relationships of valine, tert-leucine, and phenylalanine amino acid-derived synthetic cannabinoid receptor agonists related to ADB-BUTINACA, APP-BUTINACA, and ADB-P7AICA. RSC Medicinal Chemistry. 2022;13(2):156-174. DOI: 10.1039/D1MD00242B
  117. 117. Fraser J, Tittensor E. Oxazolopyridines and oxazoloquinolines. Part I. 2′-Alkyl and 2′-aryl derivatives of oxazolo(4′:5′-3:4)pyridine and oxazolo(4′:5′-3:4)quinolone. Journal of the Chemical Society. 1956:1781-1784. DOI: 10.1039/JR9560001781
  118. 118. Ruefenacht K, Kristinsson H, Mattern G. Investigations on phosphoric acid and thiophosphoric acid esters with a heterocyclic substituent. 10th and last communication. Aza analogy. II: Derivatives of oxazolo[4,5-b]pyridin-2(3H)-one, an aza analog of benzoxazol-2(3H)-one. Helvetica Chimica Acta. 1976;59(5):1593-1612
  119. 119. Clark RL, Pessolano AA, Witzel B, Lanza T, et al. 2-(substituted phenyl)oxazolo[4,5-b]pyridines and 2-(substituted phenyl)oxazolo[5,4-b]pyridines as nonacidic antiinflammatory agents. Journal of Medicinal Chemistry. 1978;21(11):1158-1162. DOI: 10.1021/jm00209a014
  120. 120. Yalçin İ, Ören İ, Şener E, Akin A, et al. The synthesis and the structure-activity relationships of some substituted benzoxazoles, oxazolo(4,5-b)pyridines, benzothiazoles and benzimidazoles as antimicrobial agents. European Journal of Medicinal Chemisty. 1992;27(4):401-406. DOI: 10.1016/0223-5234(92)90154-S
  121. 121. Tatipaka HB, Gillespie JR, Chatterjee AK, Norcross NR, et al. Substituted 2-phenylimidazopyridines: A new class of drug leads for human african trypanosomiasis. Journal of Medicinal Chemistry. 2014;57(3):828-835. DOI: 10.1021/jm401178t
  122. 122. Reen GK, Kumar A, Sharma P. In vitro and in silico evaluation of 2-(substituted phenyl) oxazolo[4,5-b]pyridine derivatives as potential antibacterial agents. Medicinal Chemistry Research. 2017;26(12):3336-3344. DOI: 10.1007/s00044-017-2026-3
  123. 123. Akbay A, Oren I, Temiz-Arpaci O, Aki-Sener E, et al. Synthesis and HIV-1 reverse transcriptase inhibitor activity of some 2,5,6-substituted benzoxazole, benzimidazole, benzothiazole and oxazolo(4,5-b)pyridine derivatives. Arzneimittel-Forschung. 2003;53(4):266-271. DOI: 10.1055/s-0031-1297107
  124. 124. Sireesha R, Tej MB, Poojith N, Sreenivasulu R, et al. Synthesis of substituted aryl incorporated oxazolo[4,5-b]pyridine-triazole derivatives: Anticancer evaluation and molecular docking studies. Polycyclic Aromatic Compounds Journal. 2021. [ahead-of-print, 1-18]. DOI: 10.1080/10406638.2021.2021256
  125. 125. Boger DL, Sato H, Lerner AE, Hedrick MP, et al. Exceptionally potent inhibitors of fatty acid amide hydrolase: The enzyme responsible for degradation of endogenous oleamide and anandamide. Proceedings of the National Academy of Sciences of the United States of America. 2000;97(10):5044-5049. DOI: 10.1073/pnas.97.10.5044
  126. 126. Boger DL, Miyauchi H, Hedrick MP. α-Keto heterocycle inhibitors of fatty acid amide hydrolase: Carbonyl group modification and α-substitution. Bioorganic & Medicinal Chemistry Letters. 2001;11(12):1517-1520. DOI: 10.1016/s0960-894x(01)00211-6
  127. 127. Pinar A, Yurdakul P, Yildiz I, Temiz-Arpaci O, et al. Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors. Biochemical and Biophysical Research Communications. 2004;317(2):670-674. DOI: 10.1016/j.bbrc.2004.03.093
  128. 128. Karatas E, Foto E, Ertan-Bolelli T, Yalcin-Ozkat G, et al. Discovery of 5-(or 6)-benzoxazoles and oxazolo[4,5-b]pyridines as novel candidate antitumor agents targeting hTopo Iiα. Bioorganic Chemistry. 2021;112:104913. DOI: 10.1016/j.bioorg.2021.104913
  129. 129. Walczyński K, Zuiderveld OP, Timmerman H. Non-imidazole histamine H3 ligands. Part III. New 4-n-propylpiperazines as non-imidazole histamine H3-antagonists. European Journal of Medicinal Chemistry. 2005;40(1):15-23. DOI: 10.1016/j.ejmech.2004.09.010
  130. 130. Vu CB, Bemis JE, Disch JS, Ng PY, et al. Discovery of ımidazo[1,2-b]thiazole derivatives as novel SIRT1 activators. Journal of Medicinal Chemistry. 2009;52(5):1275-1283. DOI: 10.1021/jm8012954
  131. 131. Park HR, Kim J, Kim T, Jo S, et al. Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease. Bioorganic & Medicinal Chemistry. 2013;21(17):5480-5487. DOI: 10.1016/j.bmc.2013.05.066
  132. 132. Tantray MA, Khan I, Hamid H, Alam MS, et al. Oxazolo[4,5-b]pyridine-based piperazinamides as GSK-3β inhibitors with potential for attenuating inflammation and suppression of pro-inflammatory mediators. Archiv der Pharmazie (Weinheim, Germany). 2017;350(8):e1700022. DOI: 10.1002/ardp.201700022
  133. 133. Qi X-Y, Cao Y, Li Y-L, Mo M-G, et al. Discovery of the selective sphingomyelin synthase 2 inhibitors with the novel structure of oxazolopyridine. Bioorganic & Medicinal Chemistry Letters. 2017;27(15):3511-3515. DOI: 10.1016/j.bmcl.2017.05.074
  134. 134. Markillie JH. Nouveaux Isoxazoles et leurs procédés de Fabrication. FR1513038. 1968
  135. 135. Nordmann R, Graff P, Maurer R, Gaehwiler BH. Synthesis and pharmacological evaluation of cis-2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo[5,4-c]pyridine: A structural analog of the GABA agonist THIP. Journal of Medicinal Chemistry. 1985;28(8):1109-1111. DOI: 10.1021/jm00146a024
  136. 136. Rajanarendar E, Raju S, Reddy MN, Krishna SR, et al. Multi-component synthesis and in vitro and in vivo anticancer activity of novel arylmethylene bis-isoxazolo[4,5-b]pyridine-N-oxides. European Journal of Medicinal Chemistry. 2012;50:274-279. DOI: 10.1016/j.ejmech.2012.02.004
  137. 137. Hanan EJ, Fucini RV, Romanowski MJ, Elling RA, et al. Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2008;18(19):5186-5189. DOI: 10.1016/j.bmcl.2008.08.091
  138. 138. Qin J, Dhondi P, Huang X, Mandal M, et al. Discovery of fused 5,6-bicyclic heterocycles as γ-secretase modulators. Bioorganic & Medicinal Chemistry Letters. 2011;21(2):664-669. DOI: 10.1016/j.bmcl.2010.12.012
  139. 139. Bailey AS, Heaton MW, Murphy JI. Preparation of a nitropyrido[3,4-c]furoxan: 7-nitro[1,2,5]oxadiazolo[3,4-c]pyridine 3-oxide. Journal of the Chemical Society [Section] C: Organic. 1971:1211-1213. DOI: 10.1039/j39710001211
  140. 140. Li Z, Huang D, Ma C, Xu X, et al. Convenient aminative ring-opening reaction of 7-amino-6-nitro-[1,2,5]oxadiazolo[3,4-b]pyridine-1-oxide and antitumor activity of corresponding products. Chinese Journal of Organic Chemistry. 2016;36(9):2236-2241. DOI: 10.6023/cjoc201602023
  141. 141. Gorohmaru H, Thiemann T, Sawada T, Takahashi K, et al. Preparation of 4,7-dihetaryl-1,2,5-oxadiazolo[3,4-c]pyridines as red fluorescent materials. Heterocycles. 2002;56(1-2):421-431. DOI: 10.3987/COM-01-S(K)64
  142. 142. Takahashi T, Yajima S. Synthesis of heterocyclic compounds of nitrogen. XXVI. Pyrimidazoles (imidazopyridines). Yakugaku Zasshi. 1946;66(2A):31
  143. 143. Vohra MM, Pradhan SN, Jain PC, Chatterjee SK, et al. Synthesis and structure-activity relations of some amino-pyridines, imidazopyridines, and triazolopyridines. Journal of Medicinal Chemistry. 1965;8(3):296-304. DOI: 10.1021/jm00327a006
  144. 144. Nakanishi M, Muro T, Nakatsu O, Nakao T, et al. Phenylalkancarbonsaeure-derivate, verfahren zu ihrer herstellung und arzneimittel. DE2432410A1. 1975
  145. 145. Kaplan J-P, George P. Imidazo(1,2-a)pyridine Derivatives, Process for their Preparation and their Therapeutical Use. EP50563 A1. 1982
  146. 146. Goto K, Hisadome M, Maruyama Y, Imamura H. Effects of 2-{4-(2-imidazo[1,2-a]pyridyl)phenyl}propionic acid (Y-9213) and antiinflammatory drugs on erythrocytes, polymorphonuclear leukocytes and lysosomes in vitro. Japanese Journal of Pharmacology. 1978;28(3):433-446. DOI: 10.1254/jjp.28.433
  147. 147. Almirante L, Polo L, Mugnaini A, Provinciali E, et al. Derivatives of imidazole. I. Synthesis and reactions of imidazo[1,2-a]pyridines with analgesic, antiinflammatory, antipyretic, and anticonvulsant activity. Journal of Medicinal Chemistry. 1965;8(3):305-312. DOI: 10.1021/jm00327a007
  148. 148. Yamanaka M, Miyake K, Suda S, Ohara H, et al. 3-Imidazo[1,2-a]pyridin-6-ylpyridine Derivatives. JP61218589 A. 1986
  149. 149. George P, Giron C. 3-Acylaminomethylimidazo[1,2-a]pyridines and Their Therapeutical Use. EP172096 A1. 1986
  150. 150. George P, Giron C. Preparation of 3-(acylaminomethyl)imidazo[1,2-a]pyridines and Pharmaceutical Compositions Containing Them as Anxiolytics, Sedatives, Analgesics, Anticonvulsants, and Ulcer inhibitors. US4650796 A. 1987
  151. 151. Isomura Y, Takeuchi M, Abe T. Heterocyclic Bisphosphonic Acid Derivatives as Bone Resorption Inhibitors. EP354806 A2. 1990
  152. 152. Bristol JA, Puchalski C. Imidazo[1,2-a]pyridines and Pharmaceutical Compositions Containing Them. EP33094 A1. 1981
  153. 153. Diederen W, Weisenberger H. Studies on the mechanism of the positive-inotropic action of AR-L 115 BS, a new cardiotonic drug. Arzneimittel-Forschung. 1981;31(1A):177-182
  154. 154. Herzig JW, Feile K, Rueegg JC. Activating effects of AR-L 115 BS on the calcium(2+) sensitive force, stiffness and unloaded shortening velocity (Vmax) in isolated contractile structures from mammalian heart muscle. Arzneimittel-Forschung. 1981;31(1A):188-191
  155. 155. Daly JW, Hong O, Padgett WL, Shamim MT, et al. Non-xanthine heterocycles: Activity as antagonists of A1- and A2-adenosine receptors. Biochemical Pharmacology. 1988;37(4):655-664. DOI: 10.1016/0006-2952(88)90139-6
  156. 156. Luo G, Dubowchik GM, Macor JE. Cycloheptapyridine Derivatives as CGRP Receptor Antagonists and Their Preparation and Use in the Treatment of CGRP-Related Diseases Such as Migraine. WO2011046997 A1. 2011
  157. 157. Burgey CS, Deng ZJ, Nguyen DN, Paone DV, et al. Preparation of Piperidine Derivatives as CGRP Receptor Antagonists. WO2004092166 A2. 2004
  158. 158. Matsuishi N, Takeda H, Iizumi K, Murakami K, et al. Preparation, Testing, and Formulation of Pyridylmethylsulfinylimidazopyridines as Ulcer Inhibitors. EP254588 A1. 1988
  159. 159. Resurii JB. Imidazo[1,5-a]pyridines. JP59118785 A. 1984
  160. 160. Bondy SS, Dahl TC, Oare DA, Oliyai R, et al. Novel Pyridazine-Containing Imidazopyridazine Compound and Uses Thereof. WO2008005519 A2. 2008
  161. 161. Dowdy ED, Kent KM, Tom NJ, Zia V. Preparation of Crystalline 5-[[6-[2,4-bis(trifluoromethyl)phenyl]-3-pyridazinyl]methyl]-2-(2-fluorophenyl)-5H-imidazo[4,5-c]pyridine for Treatment and Prophylaxis of Hepatitis C Viral Infections. WO2009009001A1. 2009
  162. 162. Shih I, Vliegen I, Peng B, Yang H, et al. Mechanistic characterization of GS-9190 (tegobuvir), a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase. Antimicrobial Agents and Chemotherapy. 2011;55(9):4196-4203. DOI: 10.1128/aac.00307-11
  163. 163. Fisher MH, Lusi A. Imidazo[1,2-a]pyridine anthelmintic and antifungal agents. Journal of Medicinal Chemistry. 1972;15(9):982-985. DOI: 10.1021/jm00279a026
  164. 164. Bochis RJ, Olen LE, Fisher MH, Reamer RA, et al. Isomeric phenylthioimidazo[1,2-a]pyridines as anthelmintics. Journal of Medicinal Chemistry. 1981;24(12):1483-1487. DOI: 10.1021/jm00144a022
  165. 165. Elhakmaoui A, Gueiffier A, Milhavet J-C, Blache Y, et al. Synthesis and antiviral activity of 3-substituted imidazo[1,2-a]pyridines. Bioorganic & Medicinal Chemistry Letters. 1994;16(4):1937-1940
  166. 166. Wang Q , Wolff M, Polat T, Du Y, et al. Inhibition of neuraminidase with neuraminic acid C-glycosides. Bioorganic & Medicinal Chemistry. 2002;10(4):941-946. DOI: 10.1016/s0960-894x(00)00132-3
  167. 167. Castera-Ducros C, Paloque L, Verhaeghe P, Casanova M, et al. Targeting the human parasite leishmania donovani: Discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series. Bioorganic & Medicinal Chemistry. 2013;21(22):7155-7164. DOI: 10.1016/j.bmc.2013.09.002
  168. 168. Jose G, Suresha Kumara TH, Nagendrappa G, Sowmya HBV, et al. New polyfunctional imidazo[4,5-C]pyridine motifs: Synthesis, crystal studies, docking studies and antimicrobial evaluation. European Journal of Medicinal Chemistry. 2014;77:288-297. DOI: 10.1016/j.ejmech.2014.03.019
  169. 169. Silva DG, Gillespie JR, Ranade RM, Herbst ZM, et al. New class of Antitrypanosomal agents based on imidazopyridines. ACS Medicinal Chemistry Letters. 2017;8(7):766-770. DOI: 10.1021/acsmedchemlett.7b00202
  170. 170. Vera B, Dashti HS, Gomez-Abellan P, Hernandez-Martinez AM, Esteban A, et al. Modifiable lifestyle behaviors, but not a genetic risk score, associate with metabolic syndrome in evening chronotypes. Scientific Reports. 2018;8(1):1-7. DOI: 10.1038/s41598-017-18268-z
  171. 171. Zhou S, Chen G, Huang G. Design, synthesis and biological evaluation of imidazo[1,2-a]pyridine analogues or derivatives as anti-helmintic drug. Chemical Biology & Drug Design. 2019;93(4):503-510. DOI: 10.1111/cbdd.13441
  172. 172. Nandikolla A, Srinivasarao S, Karan Kumar B, Murugesan S, et al. Synthesis, study of antileishmanial and antitrypanosomal activity of imidazo pyridine fused triazole analogues. RSC Advances. 2020;10(63):38328-38343. DOI: 10.1039/d0ra07881f
  173. 173. Silva DG, Junker A, de Melo SMG, Fumagalli F, et al. Front cover: Synthesis and structure-activity relationships of imidazopyridine/pyrimidine- and Furopyridine-based anti-infective agents against trypanosomiases. ChemMedChem. 2021;16(6):898. DOI: 10.1002/cmdc.202100141
  174. 174. Parcella K, Patel M, Tu Y, Eastman K, et al. Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of HIV-1 allosteric integrase inhibitors. Bioorganic & Medicinal Chemistry. 2022;67:116833. DOI: 10.1016/j.bmc.2022.116833
  175. 175. Temple CJ, Smith BH, Elliott RD, Montgomery JA. Synthesis of potential anticancer agents. Preparation of some 1-deazapurines and pyrimidines. Journal of Medicinal Chemistry. 1973;16(3):292-294. DOI: 10.1021/jm00261a031
  176. 176. Cristalli G, Franchetti P, Grifantini M, Vittori S, et al. Improved synthesis and antitumor activity of 1-deazaadenosine. Journal of Medicinal Chemistry. 1987;30(9):1686-1688. DOI: 10.1021/jm00392a029
  177. 177. Ismail MA, Arafa RK, Wenzler T, Brun R, et al. Synthesis and antiprotozoal activity of novel bis-benzamidino imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridines. Bioorganic & Medicinal Chemistry. 2008;16(2):683-691. DOI: 10.1016/j.bmc.2007.10.042
  178. 178. Dahan-Farkas N, Langley C, Rousseau AL, Yadav DB, et al. 6-Substituted imidazo[1,2-a]pyridines: Synthesis and biological activity against colon cancer cell lines HT-29 and Caco-2. European Journal of Medicinal Chemistry. 2011;46(9):4573-4583. DOI: 10.1016/j.ejmech.2011.07.036
  179. 179. Reddy Gangireddy M, Mantipally M, Gundla R, Nayak Badavath V, et al. Design and synthesis of piperazine-linked imidazo[1,2-a]pyridine derivatives as potent anticancer agents. ChemistrySelect. 2019;4(46):13622-13629. DOI: 10.1002/slct.201902955
  180. 180. Rani CS, Reddy AG, Susithra E, Mak K-K, et al. Synthesis and anticancer evaluation of amide derivatives of imidazo-pyridines. Medicinal Chemistry Research. 2021;30(1):74-83. DOI: 10.1007/s00044-020-02638-w
  181. 181. Mannem GR, Navudu R, Dubasi N, Mohammed MA, et al. Design, and synthesis of aryl derivatives of imidazopyridine-thiadiazoles as possible anticancer agents. ChemistrySelect. 2022;7(19):e202200455. DOI: 10.1002/slct.202200455
  182. 182. Wu Z, Fraley ME, Bilodeau MT, Kaufman ML, et al. Design and synthesis of 3,7-diarylimidazopyridines as inhibitors of the VEGF-receptor KDR. Bioorganic & Medicinal Chemistry Letters. 2004;14(4):909-912. DOI: 10.1016/j.bmcl.2003.12.007
  183. 183. Koltun DO, Parkhill EQ , Kalla R, Perry TD, et al. Discovery of potent and selective inhibitors of calmodulin-dependent kinase II (CaMKII). Bioorganic & Medicinal Chemistry Letters. 2018;28(3):541-546. DOI: 10.1016/j.bmcl.2017.10.040
  184. 184. Engler TA, Henry JR, Malhotra S, Cunningham B, et al. Substituted 3-imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino- [6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3. Journal of Medicinal Chemistry. 2004;47(16):3934-3937. DOI: 10.1021/jm049768a
  185. 185. Jaramillo C, De Diego JE, Hamdouchi C, Collins E, et al. Aminoimidazo[1,2-a]pyridines as a new structural class of cyclin-dependent kinase inhibitors. Part 1: Design, synthesis, and biological evaluation. Bioorganic & Medicinal Chemistry Letters. 2004;14(24):6095-6099. DOI: 10.1016/j.bmcl.2004.09.053
  186. 186. Krajcovicova S, Jorda R, Vanda D, Soural M, et al. 1,4,6-trisubstituted imidazo[4,5-c]pyridines as inhibitors of Bruton’s tyrosine kinase. European Journal of Medicinal Chemistry. 2021;211:113094. DOI: 10.1016/j.ejmech.2020.113094
  187. 187. Rhodes N, Heerding DA, Duckett DR, Eberwein DJ, et al. Characterization of an Akt kinase ınhibitor with potent pharmacodynamic and antitumor activity. Cancer Research. 2008;68(7):2366-2374. DOI: 10.1158/0008-5472.can-07-5783
  188. 188. Chen D, Wang Y, Ma Y, Xiong B, et al. Discovery of 3H-imidazo[4,5-b]pyridines as potent c-met kinase inhibitors: Design, synthesis, and biological evaluation. ChemMedChem. 2012;7(6):1057-1070. DOI: 10.1002/cmdc.201200120
  189. 189. Matsumoto S, Miyamoto N, Hirayama T, Oki H, et al. Structure-based design, synthesis, and evaluation of imidazo[1,2-b]pyridazine and imidazo[1,2-a]pyridine derivatives as novel dual c-Met and VEGFR2 kinase inhibitors. Bioorganic & Medicinal Chemistry. 2013;21(24):7686-7698. DOI: 10.1016/j.bmc.2013.10.028
  190. 190. Frett B, McConnell N, Smith CC, Wang Y, et al. Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors. European Journal of Medicinal Chemistry. 2015;94:123-131. DOI: 10.1016/j.ejmech.2015.02.052
  191. 191. Bach J, Eastwood P, Gonzalez J, Gomez E, et al. Identification of 2-imidazopyridine and 2-aminopyridone purinones as potent pan-janus kinase (JAK) inhibitors for the inhaled treatment of respiratory diseases. Journal of Medicinal Chemistry. 2019;62(20):9045-9060. DOI: 10.1021/acs.jmedchem.9b00533
  192. 192. Hayakawa M, Kaizawa H, Kawaguchi K, Ishikawa N, et al. Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110α inhibitors. Bioorganic & Medicinal Chemistry. 2007;15(1):403-412. DOI: 10.1016/j.bmc.2006.09.047
  193. 193. Bach J, Eastwood P, Gonzalez J, Gomez E, et al. Identification of 2-imidazopyridine and 2-aminopyridone purinones as potent pan-janus kinase (JAK) inhibitors for the inhaled treatment of respiratory diseases. Journal of Medicinal Chemistry. 2010;53(14):5213-5228. DOI: 10.1021/acs.jmedchem.9b00533
  194. 194. Fan Y-H, Li W, Liu D-D, Bai M-X, et al. Design, synthesis, and biological evaluation of novel 3-substituted imidazo[1,2-a]pyridine and quinazolin-4(3H)-one derivatives as PI3Kα inhibitors. European Journal of Medicinal Chemistry. 2017;139:95-106. DOI: 10.1016/j.ejmech.2017.07.074
  195. 195. Terao Y, Suzuki H, Yoshikawa M, Yashiro H, et al. Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors. Bioorganic & Medicinal Chemistry Letters. 2012;22(24):7326-7329. DOI: 10.1016/j.bmcl.2012.10.084
  196. 196. Tikhonova TA, Rassokhina IV, Kondrakhin EA, Fedosov MA, et al. Development of 1,3-thiazole analogues of imidazopyridines as potent positive allosteric modulators of GABAA receptors. Bioorganic Chemistry. 2020;94:103334. DOI: 10.1016/j.bioorg.2019.103334
  197. 197. Krenitsky TA, Rideout JL, Chao EY, Koszalka GW, et al. Imidazo[4,5-c]pyridines (3-deazapurines) and their nucleosides as immunosuppressive and antiinflammatory agents. Journal of Medicinal Chemistry. 1986;29(1):138-143. DOI: 10.1021/jm00151a022
  198. 198. Kelley JL, Linn JA, Rideout JL, Soroko FE. Synthesis and anticonvulsant activity of 1-benzyl-4-alkylamino-1H-imidazo[4,5-c]pyridines. Journal of Heterocyclic Chemistry. 1988;25(4):1255-1258. DOI: 10.1002/jhet.5570250441
  199. 199. Mantlo NB, Chakravarty PK, Ondeyka DL, Siegl PKS, et al. Potent, orally active imidazo[4,5-b]pyridine-based angiotensin II receptor antagonists. Journal of Medicinal Chemistry. 1991;34(9):2919-2922. DOI: 10.1021/jm00113a035
  200. 200. Coates WJ, Connolly B, Dhanak D, Flynn ST, et al. Cyclic nucleotide phosphodiesterase inhibition by imidazopyridines: Analogs of sulmazole and isomazole as inhibitors of the cGMP specific phosphodiesterase. Journal of Medicinal Chemistry. 1993;36(10):1387-1392. DOI: 10.1021/jm00062a011
  201. 201. Carceller E, Merlos M, Giral M, Balsa D, et al. Design, synthesis, and structure-activity relationship studies of novel 1-[(1-acyl-4-piperidinyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine derivatives as potent, orally active platelet-activating factor antagonists. Journal of Medicinal Chemistry. 1996;39(2):487-493. DOI: 10.1021/jm950555i
  202. 202. Izumi T, Sakaguchi J, Takeshita M, Tawara H, et al. 1H-Imidazo[4,5-c]quinoline derivatives as novel potent TNF-α suppressors: Synthesis and structure-activity relationship of 1-, 2-and 4-substituted 1H-imidazo[4,5-c]quinolines or 1H-imidazo[4,5-c]pyridines. Bioorganic & Medicinal Chemistry. 2003;11(12):2541-2550. DOI: 10.1016/s0968-0896(03)00178-0
  203. 203. Tresadern G, Cid JM, Macdonald GJ, Vega JA, et al. Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor. Bioorganic & Medicinal Chemistry Letters. 2010;20(1):175-179. DOI: 10.1016/j.bmcl.2009.11.008
  204. 204. Peterson EA, Boezio AA, Andrews PS, Boezio CM, et al. Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors. Bioorganic & Medicinal Chemistry Letters. 2012;22(15):4967-4974. DOI: 10.1016/j.bmcl.2012.06.033
  205. 205. Hintermann S, Guntermann C, Mattes H, Carcache DA, et al. Synthesis and biological evaluation of new triazolo- and imidazolopyridine RORγt inverse agonists. ChemMedChem. 2016;11(24):2640-2648. DOI: 10.1002/cmdc.201600500
  206. 206. Igawa H, Takahashi M, Kakegawa K, As K, et al. Melanin-concentrating hormone receptor 1 antagonists lacking an aliphatic amine: Synthesis and structure-activity relationships of novel 1-(imidazo[1,2-a]pyridin-6-yl)pyridin-2(1H)-one derivatives. Journal of Medicinal Chemistry. 2016;59(3):1116-1139. DOI: 10.1021/acs.jmedchem.5b01704
  207. 207. Joncour A, Desroy N, Housseman C, Bock X, et al. Discovery, structure-activity relationship, and binding mode of an imidazo[1,2-a]pyridine series of autotaxin inhibitors. Journal of Medicinal Chemistry. 2017;60(17):7371-7392. DOI: 10.1021/acs.jmedchem.7b00647
  208. 208. Lee JM, Choi HS, Kim ES, Keum B, et al. Characterization of irreversible electroporation on the stomach: A feasibility study in rats. Scientific Reports. 2019;9(1):1-15. DOI: 10.1038/s41598-019-54656-3
  209. 209. Shen H, Ge Y, Wang J, Li H, et al. Design, synthesis and biological evaluation of novel molecules as potent PARP-1 inhibitors. Bioorganic & Medicinal Chemistry Letters. 2021;47:128169. DOI: 10.1016/j.bmcl.2021.128169
  210. 210. Englert SME, McElvain SM. Pyrazolones derived from the carbethoxypiperidones. Journal of the American Chemical Society. 1934;56:700-702. DOI: 10.1021/ja01318a051
  211. 211. Schmidt P, Eichenberger K, Rossi A, Wilhelm M. Preparation of Pyrazolopyridines. CH416659. 1967
  212. 212. Sekikawa I, Nishie J, Tonooka S, Tanaka Y, et al. Antituberculous compounds. XXVIII. Synthesis of pyrazolopyridines. Journal of Heterocyclic Chemistry. 1973;10(6):931-932. DOI: 10.1002/jhet.5570100607
  213. 213. Gudmundsson KS, Johns BA, Wang Z, Turner EM, et al. Synthesis of novel substituted 2-phenylpyrazolopyridines with potent activity against herpesviruses. Bioorganic & Medicinal Chemistry. 2005;13(18):5346-5361. DOI: 10.1016/j.bmc.2005.05.043
  214. 214. El-borai MA, Rizk HF, Abd-Aal MF, El-Deeb IY. Synthesis of pyrazolo[3,4-b]pyridines under microwave irradiation in multi-component reactions and their antitumor and antimicrobial activities. Part 1. European Journal of Medicinal Chemistry. 2012;48:92-96. DOI: 10.1016/j.ejmech.2011.11.038
  215. 215. Quiroga J, Villarreal Y, Galvez J, Ortiz A, et al. Synthesis and antifungal in vitro evaluation of pyrazolo[3,4-b]pyridines derivatives obtained by aza-Diels-Alder reaction and microwave irradiation. Chemical & Pharmaceutical Bulletin. 2017;65(2):143-150. DOI: 10.1248/cpb.c16-00652
  216. 216. Hu Y, Kitamura N, Musharrafieh R, Wang J. Discovery of potent and broad-spectrum pyrazolopyridine-containing antivirals against enteroviruses D68, A71, and coxsackievirus B3 by targeting the viral 2C protein. Journal of Medicinal Chemistry. 2021;64(12):8755-8774. DOI: 10.1021/acs.jmedchem.1c00758
  217. 217. Niemand J, van Biljon R, van der Watt M, van Heerden A, et al. Chemogenomic fingerprints associated with stage-specific gametocytocidal compound action against human malaria parasites. ACS Infectious Diseases. 2021;7(10):2904-2916. DOI: 10.1021/acsinfecdis.1c00373
  218. 218. Sanghvi YS, Larson SB, Willis RC, Robins RK, et al. Synthesis and biological evaluation of certain C-4 substituted pyrazolo[3,4-b]pyridine nucleosides. Journal of Medicinal Chemistry. 1989;32(5):945-951. DOI: 10.1021/jm00125a004
  219. 219. Mohamed AM, El-Sayed WA, Alsharari MA, Al-Qalawi HRM, et al. Anticancer activities of some newly synthesized pyrazole and pyrimidine derivatives. Archives of Pharmacal Research. 2013;36(9):1055-1065. DOI: 10.1007/s12272-013-0163-x
  220. 220. Milisiunaite V, Arbaciauskiene E, Reznickova E, Jorda R, et al. Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines. European Journal of Medicinal Chemistry. 2018;150:908-919. DOI: 10.1016/j.ejmech.2018.03.037
  221. 221. Abozeid MA, El-Sawi AA, Abdelmoteleb M, Awad H, et al. Synthesis of novel naphthalene-heterocycle hybrids with potent antitumor, anti-inflammatory and antituberculosis activities. RSC Advances. 2020;10(70):42998-43009. DOI: 10.1039/d0ra08526j
  222. 222. Papastathopoulos A, Lougiakis N, Kostakis IK, Marakos P, et al. New bioactive 5-arylcarboximidamidopyrazolo[3,4-c]pyridines: Synthesis, cytotoxic activity, mechanistic investigation and structure-activity relationships. European Journal of Medicinal Chemistry. 2021;218:113387. DOI: 10.1016/j.ejmech.2021.113387
  223. 223. Misra RN, Rawlins DB, Xiao H, Shan W, et al. 1H-pyrazolo[3,4-b]pyridine ınhibitors of cyclin-dependent kinases. Bioorganic & Medicinal Chemistry Letters. 2003;13(6):1133-1136. DOI: 10.1016/s0960-894x(03)00034-9
  224. 224. Witherington J, Bordas V, Garland SL, Hickey DMB, et al. 5-aryl-pyrazolo[3,4-b]pyridines: Potent inhibitors of glycogen synthase kinase-3 (GSK-3). Bioorganic & Medicinal Chemistry Letters. 2003;13(9):1577-1580. DOI: 10.1016/S0960-894X(03)00134-3
  225. 225. Collier PN, Twin HC, Knegtel RMA, Boyall D, et al. Discovery of selective, orally bioavailable pyrazolopyridine inhibitors of protein kinase Cθ (PKCθ) that ameliorate symptoms of experimental autoimmune encephalomyelitis. ACS Medicinal Chemistry Letters. 2019;10(8):1134-1139. DOI: 10.1021/acsmedchemlett.9b00134
  226. 226. Gilbert AM, Nowak P, Brooijmans N, Bursavich MG, et al. Novel purine and pyrazolo[3,4-d]pyrimidine inhibitors of PI3 kinase-α: Hit to lead studies. Bioorganic & Medicinal Chemistry Letters. 2010;20(2):636-639. DOI: 10.1016/j.bmcl.2009.11.051
  227. 227. Shi J, Xu G, Zhu W, Ye H, et al. Design and synthesis of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and pyrazolo[3,4-b]pyridines for Aurora-a kinase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2010;20(14):4273-4278. DOI: 10.1016/j.bmcl.2010.04.083
  228. 228. Nishiguchi GA, Atallah G, Bellamacina C, Burger MT, et al. Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases. Bioorganic & Medicinal Chemistry Letters. 2011;21(21):6366-6369. DOI: 10.1016/j.bmcl.2011.08.105
  229. 229. Yogo T, Nagamiya H, Seto M, Sasaki S, et al. Structure-based design and synthesis of 3-amino-1,5-dihydro-4H-pyrazolopyridin-4-one derivatives as tyrosine kinase 2 inhibitors. Journal of Medicinal Chemistry. 2016;59(2):733-749. DOI: 10.1021/acs.jmedchem.5b01857
  230. 230. Sabat M, Wang H, Scorah N, Lawson JD, et al. Design, synthesis and optimization of 7-substituted-pyrazolo[4,3-b]pyridine ALK5 (activin receptor-like kinase 5) inhibitors. Bioorganic & Medicinal Chemistry Letters. 2017;27(9):1955-1961. DOI: 10.1016/j.bmcl.2017.03.026
  231. 231. Nam Y, Hwang D, Kim N, Seo H-S, et al. Identification of 1H-pyrazolo[3,4-b]pyridine derivatives as potent ALK-L1196M inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2019;34(1):1426-1438. DOI: 10.1080/14756366.2019.1639694
  232. 232. Pfaffenrot B, Kloevekorn P, Juchum M, Selig R, et al. Design and synthesis of 1H-pyrazolo[3,4-b]pyridines targeting mitogen-activated protein kinase kinase 4 (MKK4)—A promising target for liver regeneration. European Journal of Medicinal Chemistry. 2021;218:113371. DOI: 10.1016/j.ejmech.2021.113371
  233. 233. Bare TM, McLaren CD, Campbell JB, Firor JW, et al. Synthesis and structure-activity relationships of a series of anxioselective pyrazolopyridine ester and amide anxiolytic agents. Journal of Medicinal Chemistry. 1989;32(12):2561-2573. DOI: 10.1021/jm00132a011
  234. 234. Akahane A, Katayama H, Mitsunaga T, Kita Y, et al. Discovery of FK453, a novel non-xanthine adenosine A1 receptor antagonist. Bioorganic & Medicinal Chemistry Letters. 1996;6(17):2059-2062. DOI: 10.1016/0960-894x(96)00368-x
  235. 235. Ochiai H, Ishida A, Ohtani T, Kusumi K, et al. New orally active PDE4 inhibitors with therapeutic potential. Bioorganic & Medicinal Chemistry Letters. 2004;14(1):29-32. DOI: 10.1016/j.bmcl.2003.10.025
  236. 236. Yu G, Mason HJ, Wu X, Wang J, et al. Substituted pyrazolopyridines as potent and selective PDE5 inhibitors: Potential agents for treatment of erectile dysfunction. Journal of Medicinal Chemistry. 2001;44(7):1025-1027. DOI: 10.1021/jm0155042
  237. 237. Wu Y, Zhou Q , Zhang T, Li Z, et al. Discovery of potent, selective, and orally bioavailable inhibitors against phosphodiesterase-9, a novel target for the treatment of vascular dementia. Journal of Medicinal Chemistry. 2019;62(8):4218-4224. DOI: 10.1021/acs.jmedchem.8b01041
  238. 238. Kaplan J, Verheijen JC, Brooijmans N, Toral-Barza L, et al. Discovery of 3,6-dihydro-2H-pyran as a morpholine replacement in 6-aryl-1H-pyrazolo[3,4-d]pyrimidines and 2-arylthieno[3,2-d]pyrimidines: ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Bioorganic & Medicinal Chemistry Letters. 2010;20(2):640-643. DOI: 10.1016/j.bmcl.2009.11.050
  239. 239. Griebenow N, Schirok H, Mittendorf J, Alexander S, et al. Identification of acidic heterocycle-substituted 1H-pyrazolo[3,4-b]pyridines as soluble guanylate cyclase stimulators. Bioorganic & Medicinal Chemistry Letters. 2013;23(5):1197-1200. DOI: 10.1016/j.bmcl.2013.01.028
  240. 240. Wenglowsky S, Ahrendt KA, Buckmelter AJ, Feng B, et al. Pyrazolopyridine inhibitors of B-RafV600E. Part 2: Structure-activity relationships. Bioorganic & Medicinal Chemistry Letters. 2011;21(18):5533-5537. DOI: 10.1016/j.bmcl.2011.06.097
  241. 241. Wenglowsky S, Li R, Ahrendt KA, Laird ER, et al. Pyrazolopyridine inhibitors of B-RafV600E. Part 1: The development of selective, orally bioavailable, and efficacious inhibitors. ACS Medicinal Chemistry Letters. 2011;2(5):342-347. DOI: 10.1021/ml200025q
  242. 242. Elsner J, Boeckler F, Heinemann FW, Huebner H, et al. Pharmacophore-guided drug discovery investigations leading to bioactive 5-aminotetrahydropyrazolopyridines. Implications for the binding mode of heterocyclic dopamine D3 receptor agonists. Journal of Medicinal Chemistry. 2005;48(18):5771-5779. DOI: 10.1021/jm0503805
  243. 243. Zhai M, Liu S, Gao M, Wang L, et al. 3,5-Diaryl-1H-pyrazolo[3,4-b]pyridines as potent tubulin polymerization inhibitors: Rational design, synthesis and biological evaluation. European Journal of Medicinal Chemistry. 2019;168:426-435. DOI: 10.1016/j.ejmech.2018.12.053
  244. 244. Pan T, Xie S, Zhou Y, Hu J, et al. Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer’s disease: Design, synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids. Bioorganic & Medicinal Chemistry Letters. 2019;29(16):2150-2152. DOI: 10.1016/j.bmcl.2019.06.056
  245. 245. Saikachi H. Pyridine derivatives containing sulfur. VII. Syntheses of pyridoxazoles and pyridothiazoles. Yakugaku Zasshi. 1944;64:201-202
  246. 246. Ozawa S. Antituberculous activity of heterocyclic compounds. IV. Pyridine, pyridothiazole, phenylpyridyl ether, nicotinoyl hydrazide, and isonicotinoyl hydrazide derivatives. Kyoto Daigaku Kekkaku Kenkyusho Nempo. 1956;4:284-294
  247. 247. Leysen DC, Haemers A, BollaertW. Thiazolopyridine analogs of nalidixic acid. 1. Thiazolo[5,4-b]pyridines. Journal of Heterocyclic Chemistry. 1984;21(2):401-406. DOI: 10.1002/jhet.5570210226
  248. 248. El-Hag Ali GAM, Khalil A, Ahmed AHA, El-Gaby MSA. Studies on thiazolopyridines. Part 2. Synthesis and antimicrobial activity of novel thiazolo[3,2-a]pyridine and thiazolo[3,2-a][1,8]naphthyridine derivatives having two different aryl moieties. Acta Chimica Slovenica. 2002;49(2):365-376
  249. 249. Chaban T, Klenina O, Drapak I, Ogurtsov V, et al. Synthesis of some novel thiazolo[4,5-b]pyridines and their tuberculostatic activity evaluation. Chemistry & Chemical Technology. 2014;8(3):287-292. DOI: 10.23939/chcht08.03.287
  250. 250. El-Mawgoud HKA. Synthesis, in-vitro cytotoxicity and antimicrobial evaluations of some novel thiazole based heterocycles. Chemical & Pharmaceutical Bulletin. 2019;67(12):1314-1323. DOI: 10.1248/cpb.c19-00681
  251. 251. Othman IMM, Gad-Elkareem MAM, Radwan HA, Badraoui R, et al. Synthesis, structure-activity relationship and in silico studies of novel pyrazolothiazole and thiazolopyridine derivatives as prospective antimicrobial and anticancer agents. ChemistrySelect. 2021;6(31):7860-7872. DOI: 10.1002/slct.202101622
  252. 252. Shi F, Li C, Xia M, Miao K, et al. Green chemoselective synthesis of thiazolo[3,2-a]pyridine derivatives and evaluation of their antioxidant and cytotoxic activities. Bioorganic & Medicinal Chemistry Letters. 2009;19(19):5565-5568. DOI: 10.1016/j.bmcl.2009.08.046
  253. 253. Lozynskyi A, Zimenkovsky B, Ivasechko I, Senkiv J, et al. Synthesis and cytotoxicity of new 2-oxo-7-phenyl-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid amides. Phosphorus, Sulfur and Silicon and the Related Elements. 2019;194(12):1149-1157. DOI: 10.1080/10426507.2019.1633318
  254. 254. Yahia HB, Sabri S, Essehli R, Kasak P, et al. Crystal growth, single crystal structure, and biological activity of thiazolo-pyridine dicarboxylic acid derivatives. ACS Omega. 2020;5(43):27756-27765. DOI: 10.1021/acsomega.0c01769
  255. 255. Raslan RR, Hessein SA, Fouad SA, Shmiess NAM. Synthesis and antitumor evaluation of some new thiazolopyridine, nicotinonitrile, pyrazolopyridine, and polyhydroquinoline derivatives using ceric ammonium nitrate as a green catalyst. Journal of Heterocyclic Chemistry. 2022;59(5):832-846. DOI: 10.1002/jhet.4423
  256. 256. Kulkarni SS, Newman AH. Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists. Bioorganic & Medicinal Chemistry Letters. 2007;17(11):2987-2991. DOI: 10.1016/j.bmcl.2007.03.066
  257. 257. Cee VJ, Lin J, Yu XY, Zhang Z. S1p1 Receptor Agonists and Use Thereof. WO2009154775 A1. 2012
  258. 258. Kale MG, Raichurkar A, Shahul HP, Waterson D, et al. Thiazolopyridine ureas as novel antitubercular agents acting through inhibition of DNA gyrase B. Journal of Medicinal Chemistry. 2013;56(21):8834-8848. DOI: 10.1021/jm401268f
  259. 259. Chaban TI, Ogurtsov VV, Matiychuk VS, Chaban IG, et al. Synthesis, anti-inflammatory and antioxidant activities of novel 3H-thiazolo[4,5-b]pyridines. Acta Chimica Slovenica. 2019;66(1):103-111. DOI: 10.17344/acsi.2018.4570
  260. 260. Zhu J, Li K, Xu L, Jin J. Insight into the selective mechanism of phosphoinositide 3-kinase γ with benzothiazole and thiazolopiperidine γ-specific inhibitors by in silico approaches. Chemical Biology & Drug Design. 2019;93(5):818-831. DOI: 10.1111/cbdd.13469
  261. 261. Scott DA, Hatcher JM, Liu H, Fu M, et al. Quinoline and thiazolopyridine allosteric inhibitors of MALT1. Bioorganic & Medicinal Chemistry Letters. 2019;29(14):1694-1698. DOI: 10.1016/j.bmcl.2019.05.040
  262. 262. Taurins A, Khouw VT, Isothiazolopyridines I. Synthesis and spectra of isothiazolo[3,4-b]-, 3-aminoisothiazolo[4,3-b]-, isothiazolo[5,4-b]-, and 3-methylisothiazolo[5,4-c]pyridines. Preparation and spectra of some 2,3 and 3,4-disubstituted pyridines. Canadian Journal of Chemistry. 1973;51(11):1741-1748. DOI: 10.1139/v73-262
  263. 263. Malinka W, Rutkowska M. Synthesis and anorectic activity of 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridine. Farmaco. 1997;52(10):595-601
  264. 264. Ghorab M-M, Hassan A-Y, Nassar O-M. Synthesis of novel heterocyclic compounds for antitumor and radioprotective activities. Phosphorus, Sulfur and Silicon and the Related Elements. 1998;134(135):447-462. DOI: 10.1080/10426509808545486
  265. 265. Malinka W, Sieklucka-Dziuba M, Rajtar G, Zgodzinski W, et al. Synthesis and preliminary screening of derivatives of 2-(4-arylpiperazin-1-ylalkyl)-3-oxoisothiazolo[5,4-b]pyridines as CNS and antimycobacterial agents. Die Pharmazie. 2000;55(6):416-425
  266. 266. Malinka W, Swiatek P, Filipek B, Sapa J, et al. Synthesis, analgesic activity and computational study of new isothiazolopyridines of Mannich base type. Farmaco. 2005;60(11-12):961-968. DOI: 10.1016/j.farmac.2005.08.005
  267. 267. Li J, Kovackova S, Pu S, Rozenski J, et al. Isothiazolo[4,3-b]pyridines as inhibitors of cyclin G associated kinase: Synthesis, structure-activity relationship studies and antiviral activity. MedChemComm. 2015;6(9):1666-1672. DOI: 10.1039/C5MD00229J
  268. 268. Martinez-Gualda B, Saul S, Froeyen M, Schols D, et al. Discovery of 3-phenyl- and 3-N-piperidinyl-isothiazolo[4,3-b]pyridines as highly potent inhibitors of cyclin G-associated kinase. European Journal of Medicinal Chemistry. 2021;213:113158. DOI: 10.1016/j.ejmech.2021.113158
  269. 269. Swiatek P, Strzelecka M, Urniaz R, Gebczak K, et al. Synthesis, COX-1/2 inhibition activities and molecular docking study of isothiazolopyridine derivatives. Bioorganic & Medicinal Chemistry. 2016;25(1):316-326. DOI: 10.1016/j.bmc.2016.10.036
  270. 270. Reitmann J. Pyridine compounds with analeptic action. Medizin und Chemie. Abhandlungen aus den Medizinisch-chemischen Forschungsstätten der I.G. Farbenindustrie Aktiengesellschaft. 1936;3:399-402
  271. 271. Palazzo G, Silvestrini B. S-Triazolo[4,3-a]pyridines. US3381009 A. 1968
  272. 272. Akbari V, Ghobadi S, Mohammadi S, Khodarahmi R. The antidepressant drug; trazodone inhibits tau amyloidogenesis: Prospects for prophylaxis and treatment of AD. Archives of Biochemistry and Biophysics. 2020;679:108218. DOI: 10.1016/j.abb.2019.108218
  273. 273. Sadana AK, Mirza Y, Aneja KR, Prakash O. Hypervalent iodine mediated synthesis of 1-aryl/hetaryl-1,2,4-triazolo[4,3-a]pyridines and 1-aryl/hetaryl-5-methyl-1,2,4-triazolo[4,3-a]quinolines as antibacterial agents. European Journal of Medicinal Chemistry. 2003;38(5):533-536. DOI: 10.1016/S0223-5234(03)00061-8
  274. 274. East SP, White CB, Barker O, Barker S, et al. DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: Synthesis and antibacterial activity. Bioorganic & Medicinal Chemistry Letters. 2009;19(3):894-899. DOI: 10.1016/j.bmcl.2008.11.102
  275. 275. Liu X-H, Sun Z-H, Yang M-Y, Tan C-X, et al. Microwave assistant one pot synthesis, crystal structure, antifungal activities and 3D-QSAR of novel 1,2,4-triazolo[4,3-a]pyridines. Chemical Biology & Drug Design. 2014;84(3):342-347. DOI: 10.1111/cbdd.12323
  276. 276. Hudson NO, Buck-Koehntop BA. Zinc finger readers of methylated DNA. Molecules. 2018;23(10):1-15. DOI: 10.3390/molecules23102555
  277. 277. Hartwich A, Zdzienicka N, Schols D, Andrei G, et al. Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5-b]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-b]pyridin-2(3H)-one systems. Nucleosides, Nucleotides & Nucleic Acids. 2020;39(4):542-591. DOI: 10.1080/15257770.2019.1669046
  278. 278. Butani SC, Vekariya MK, Dholaria PV, Kapadiya KM, et al. Copper(I)-catalyzed click chemistry-based synthesis and antimicrobial evaluation of triazolopyridine-triazole congeners. Russian Journal of Organic Chemistry. 2022;58(3):405-411. DOI: 10.1134/s1070428022030204
  279. 279. Zhang G, Hu Y. Synthesis and antitumor activities of 2-(substituted)phenyl-1,2,4-triazolo[1,5-a]pyridines. Journal of Heterocyclic Chemistry. 2007;44(4):919-922. DOI: 10.1002/jhet.5570440428
  280. 280. Sachdeva T, Low ML, Mai C-W, Cheong SL, et al. Design, synthesis and characterisation of novel phenothiazine-based triazolopyridine derivatives: Evaluation of anti-breast cancer activity on human breast carcinoma. ChemistrySelect. 2019;4(43):12701-12707. DOI: 10.1002/slct.201903203
  281. 281. Tian N, Wu H, Zhang H, Yang D, et al. Discovery of [1,2,4]triazolo[4,3-a]pyridines as potent smoothened inhibitors targeting the hedgehog pathway with improved antitumor activity in vivo. Bioorganic & Medicinal Chemistry. 2020;28(16):115584. DOI: 10.1016/j.bmc.2020.115584
  282. 282. Pastor J, Oyarzabal J, Saluste G, Alvarez RM, et al. Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2012;22(4):1591-1597. DOI: 10.1016/j.bmcl.2011.12.130
  283. 283. Menet CJ, Fletcher SR, Van Lommen G, Geney R, et al. Triazolopyridines as selective JAK1 inhibitors: From hit ıdentification to GLPG0634. Journal of Medicinal Chemistry. 2014;57(22):9323-9342. DOI: 10.1021/jm501262q
  284. 284. Dugan BJ, Gingrich DE, Mesaros EF, Milkiewicz KL, et al. A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of janus kinase 2 for use in anticancer therapy: Discovery of CEP-33779. Journal of Medicinal Chemistry. 2012;55(11):5243-5254. DOI: 10.1021/jm300248q
  285. 285. Ellard K, Sunose M, Bell K, Ramsden N, et al. Discovery of novel PI3Kγ/δ inhibitors as potential agents for inflammation. Bioorganic & Medicinal Chemistry Letters. 2012;22(14):4546-4549. DOI: 10.1016/j.bmcl.2012.05.121
  286. 286. Krishnaiah M, Jin CH, Sreenu D, Subrahmanyam VB, et al. Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors. European Journal of Medicinal Chemistry. 2012;57:74-84. DOI: 10.1016/j.ejmech.2012.09.011
  287. 287. Oguro Y, Cary DR, Miyamoto N, Tawada M, et al. Design, synthesis, and evaluation of novel VEGFR2 kinase inhibitors: Discovery of [1,2,4]triazolo[1,5-a]pyridine derivatives with slow dissociation kinetics. Bioorganic & Medicinal Chemistry. 2013;21(15):4714-4729. DOI: 10.1016/j.bmc.2013.04.042
  288. 288. Ferguson GD, Delgado M, Plantevin-Krenitsky V, Jensen-Pergakes K, et al. A novel triazolopyridine-based spleen tyrosine kinase inhibitor that arrests joint inflammation. PLoS One. 2016;11(1):e0145705/1-e0145705/24. DOI: 10.1371/journal.pone.0145705
  289. 289. Zhao J, Fang L, Zhang X, Liang Y, et al. Synthesis and biological evaluation of new [1,2,4]triazolo[4,3-a]pyridine derivatives as potential c-Met inhibitors. Bioorganic & Medicinal Chemistry. 2016;24(16):3483-3493. DOI: 10.1016/j.bmc.2016.05.057
  290. 290. Schulze VK, Klar U, Kosemund D, Wengner AM, et al. Treating cancer by spindle assembly checkpoint abrogation: Discovery of two clinical candidates, BAY 1161909 and BAY 1217389, targeting MPS1 kinase. Journal of Medicinal Chemistry. 2020;63(15):8025-8042. DOI: 10.1021/acs.jmedchem.9b02035
  291. 291. Nettekoven M. Combinatorial synthesis of 5-aryl-[1,2,4]-triazolo-[1,5-a]-pyridine derivatives as potential inhibitors of the adenosine 2a receptor. Synlett. 2001;12:1917-1920. DOI: 10.1055/s-2001-18758
  292. 292. Shaik K, Deb PK, Mailavaram RP, Chandrasekaran B, et al. 7-Amino-2-aryl/hetero-aryl-5-oxo-5,8-dihydro[1,2,4]triazolo[1,5-a]pyridine-6-carbonitriles: Synthesis and adenosine receptor binding studies. Chemical Biology & Drug Design. 2019;94(2):1568-1573. DOI: 10.1111/cbdd.13528
  293. 293. Dombroski MA, Duplantier AJ, Laird ER, Letavic MA, et al. Preparation of 6-(phenylheterocyclyl)-[1,2,4]triazolo[4,3-a]pyridines as Anti-Inflammatory Agents. WO2002072579 A1. 2002
  294. 294. McClure KF, Abramov YA, Laird ER, Barberia JT, et al. Theoretical and experimental design of atypical kinase inhibitors: Application to p38 MAP kinase. Journal of Medicinal Chemistry. 2005;48(18):5728-5737. DOI: 10.1021/jm050346q
  295. 295. Wang H, Robl JA, Hamann LG, Simpkins L, et al. Generation of 3,8-substituted 1,2,4-triazolopyridines as potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1). Bioorganic & Medicinal Chemistry Letters. 2011;21(14):4146-4149. DOI: 10.1016/j.bmcl.2011.05.101
  296. 296. Andres J-I, Alcazar J, Cid JM, De Angelis M, et al. Synthesis, evaluation, and radiolabeling of new potent positive allosteric modulators of the metabotropic glutamate receptor 2 as potential tracers for positron emission tomography imaging. Journal of Medicinal Chemistry. 2012;55(20):8685-8699. DOI: 10.1021/jm300912k
  297. 297. Engers JL, Bender AM, Kalbfleisch JJ, Cho HP, et al. Discovery of tricyclic triazolo- and ımidazopyridine lactams as M1 positive allosteric modulators. ACS Chemical Neuroscience. 2019;10(3):1035-1042. DOI: 10.1021/acschemneuro.8b00311
  298. 298. Ahmed S, Ayscough A, Barker GR, Canning HE, et al. 1,2,4-triazolo-[1,5-a]pyridine HIF prolylhydroxylase domain-1 (PHD-1) ınhibitors with a novel monodentate binding ınteraction. Journal of Medicinal Chemistry. 2017;60(13):5663-5672. DOI: 10.1021/acs.jmedchem.7b00352
  299. 299. Wurtz NR, Viet A, Shaw SA, Dilger A, et al. Potent triazolopyridine myeloperoxidase inhibitors. ACS Medicinal Chemistry Letters. 2018;9(12):1175-1180. DOI: 10.1021/acsmedchemlett.8b00308
  300. 300. Nakajima R, Oono H, Sugiyama S, Matsueda Y, et al. Discovery of [1,2,4]triazolo[1,5-a]pyridine derivatives as potent and orally bioavailable RORγt inverse agonists. ACS Medicinal Chemistry Letters. 2020;11(4):528-534. DOI: 10.1021/acsmedchemlett.9b00649
  301. 301. Yang F, Jian X-E, Diao P-C, Huo X-S, et al. Synthesis, and biological evaluation of 3,6-diaryl-[1,2,4]triazolo[4,3-a]pyridine analogues as new potent tubulin polymerization inhibitors. European Journal of Medicinal Chemistry. 2020;204:112625. DOI: 10.1016/j.ejmech.2020.112625
  302. 302. Huang Y, Sendzik M, Zhang J, Gao Z, et al. Discovery of the clinical candidate MAK683: An EED-directed, allosteric, and selective PRC2 inhibitor for the treatment of advanced malignancies. Journal of Medicinal Chemistry. 2022;65(7):5317-5333. DOI: 10.1021/acs.jmedchem.1c02148
  303. 303. Tian C, Zhang G, Xia Z, Chen N, et al. Identification of triazolopyridine derivatives as a new class of AhR agonists and evaluation of anti-psoriasis effect in a mouse model. European Journal of Medicinal Chemistry. 2022;213:114122. DOI: 10.1016/j.ejmech.2022.114122
  304. 304. Mahmoud MR, El-Shahawi MM, Abu El-Azm FS, Abdeen MJ. Synthesis and antimicrobial activity of polyfunctionally substituted heterocyclic compounds derived from 5-cinnamoylamino-2-cyanomethyl-1,3,4-thiadiazole. Journal of Heterocyclic Chemistry. 2017;54(4):2352-2359. DOI: 10.1002/jhet.2824
  305. 305. Pabba J, Rempel BP, Withers SG, Vasella A. Synthesis of glycaro-1,5-lactams and tetrahydrotetrazolopyridine-5-carboxylates: Inhibitors of β-D-glucuronidase and α-L-iduronidase. Helvetica Chimica Acta. 2006;89(4):635-666. DOI: 10.1002/hlca.200690066
  306. 306. Zhou M, Ji S, Wu Z, Li Y, et al. Synthesis of selenazolopyridine derivatives with capability to induce apoptosis in human breast carcinoma MCF-7 cells through scavenge of intracellular ROS. European Journal of Medicinal Chemistry. 2015;96:92-97. DOI: 10.1016/j.ejmech.2015.03.069
  307. 307. Tong YC. Preparation of 1,3-Dithiolo- and 1,4-Dithiinopyridines as Industrial Antimicrobials. US5171743 A. 1992

Written By

Huseyin Istanbullu, Gulsah Bayraktar and Merve Saylam

Submitted: 14 August 2022 Reviewed: 01 September 2022 Published: 13 October 2022

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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