Synthetic and Pharmacological Expedition of Pyrazolo[1,5-a]pyridine: A
Comprehensive Review

Neetu      Agrawal; Dimple      Bansal; Vertika      Gautam
doi:10.2174/1570180820666230803101948
Abstract

Fused nitrogen-containing heterocyclic compounds have been identified to display a prominent role in medicinal chemistry, biochemistry, and other streams of science. Countless derivatives of pyrazolo[ 1,5-a] pyridine have been investigated by researchers for their distinct pharmacological characterization. In this article, we have revealed and arranged the various routes of synthesis and therapeutic activities such as dopamine binding affinity, kinase inhibitory activity, and PDE inhibitors of pyrazolo[1,5- a]pyridine-containing compounds which have been explored till now. The remarkable outcomes obtained via in vitro as well as in vivo profile screening of this moiety and its derivatives lead this scaffold to be recognized to a greater extent and examined further for better results. This review will give medicinal chemists a flying-bird eye catch view of pyrazolo[1,5-a] pyridine derivatives which will help them to design and synthesize potential compounds bearing this moiety.
Keywords: Pyrazolo[1, 5-a] pyridine, synthetic methods, kinase inhibitor, PDE inhibitor, dopamine affinity, biological activities.
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[1]
Behbehani, H.; Ibrahim, H.M. Synthetic Strategy for Pyrazolo[1,5- a]pyridine and Pyrido[1,2- b]indazole Derivatives through AcOH and O 2 -Promoted Cross-dehydrogenative Coupling Reactions between 1,3-Dicarbonyl Compounds and N -Amino-2-iminopyridines. ACS Omega,  2019, 4(12), 15289-15303.
 [http://dx.doi.org/10.1021/acsomega.9b02430] [PMID:  31552376]

[2]
Balkenhohl, M.; Salgues, B.; Hirai, T.; Karaghiosoff, K.; Knochel, P. Regioselective Metalation and Functionalization of the Pyrazolo[1,5- a]pyridine Scaffold Using Mg- and Zn-TMP Bases. Org. Lett.,  2018, 20(10), 3114-3118.
 [http://dx.doi.org/10.1021/acs.orglett.8b01204] [PMID:  29738248]

[3]
Chai, W.; Breitenbucher, J.G.; Kwok, A.; Li, X.; Wong, V.; Carruthers, N.I.; Lovenberg, T.W.; Mazur, C.; Wilson, S.J.; Axe, F.U.; Jones, T.K. Non-imidazole heterocyclic histamine H3 receptor antagonists. Bioorg. Med. Chem. Lett.,  2003, 13(10), 1767-1770.
 [http://dx.doi.org/10.1016/S0960-894X(03)00299-3] [PMID:  12729661]

[4]
Löber, S.; Hübner, H.; Utz, W.; Gmeiner, P. Rationally based efficacy tuning of selective dopamine d4 receptor ligands leading to the complete antagonist 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 213). J. Med. Chem.,  2001, 44(17), 2691-2694.
 [http://dx.doi.org/10.1021/jm015522j] [PMID:  11495580]

[5]
Taguchi, R.; Shikata, K.; Furuya, Y.; Hirakawa, T.; Ino, M.; Shin, K.; Shibata, H. Selective corticotropin-releasing factor 1 receptor antagonist E2508 reduces restraint stress-induced defecation and visceral pain in rat models. Psychoneuroendocrinology,  2017, 75, 110-115.
 [http://dx.doi.org/10.1016/j.psyneuen.2016.10.025] [PMID:  27810704]

[6]
Takahashi, Y.; Hashizume, M.; Shin, K.; Terauchi, T.; Takeda, K.; Hibi, S.; Murata-Tai, K.; Fujisawa, M.; Shikata, K.; Taguchi, R.; Ino, M.; Shibata, H.; Yonaga, M. Design, synthesis, and structure-activity relationships of novel pyrazolo[5,1-b]thiazole derivatives as potent and orally active corticotropin-releasing factor 1 receptor antagonists. J. Med. Chem.,  2012, 55(19), 8450-8463.
 [http://dx.doi.org/10.1021/jm300864p] [PMID:  22971011]

[7]
Kendall, J.D.; O’Connor, P.D.; Marshall, A.J.; Frédérick, R.; Marshall, E.S.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Chao, M.; Malik, A.; Yu, S.; Chaussade, C.; Buchanan, C.; Rewcastle, G.W.; Baguley, B.C.; Flanagan, J.U.; Jamieson, S.M.F.; Denny, W.A.; Shepherd, P.R. Discovery of pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors. Bioorg. Med. Chem.,  2012, 20(1), 69-85.
 [http://dx.doi.org/10.1016/j.bmc.2011.11.029] [PMID:  22177405]

[8]
O’Malley, D.P.; Ahuja, V.; Fink, B.; Cao, C.; Wang, C.; Swanson, J.; Wee, S.; Gavai, A.V.; Tokarski, J.; Critton, D.; Paiva, A.A.; Johnson, B.M.; Szapiel, N.; Xie, D. Discovery of Pyridazinone and Pyrazolo[1,5- a]pyridine Inhibitors of C-Terminal Src Kinase. ACS Med. Chem. Lett.,  2019, 10(10), 1486-1491.
 [http://dx.doi.org/10.1021/acsmedchemlett.9b00354] [PMID:  31620238]

[9]
Stevens, K.L.; Jung, D.K.; Alberti, M.J.; Badiang, J.G.; Peckham, G.E.; Veal, J.M.; Cheung, M.; Harris, P.A.; Chamberlain, S.D.; Peel, M.R. Pyrazolo[1,5-a]pyridines as p38 kinase inhibitors. Org. Lett.,  2005, 7(21), 4753-4756.
 [http://dx.doi.org/10.1021/ol0519745] [PMID:  16209527]

[10]
Allcock, R.W.; Blakli, H.; Jiang, Z.; Johnston, K.A.; Morgan, K.M.; Rosair, G.M.; Iwase, K.; Kohno, Y.; Adams, D.R. Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast. Bioorg. Med. Chem. Lett.,  2011, 21(11), 3307-3312.
 [http://dx.doi.org/10.1016/j.bmcl.2011.04.021] [PMID:  21530250]

[11]
Johnston, K.A.; Allcock, R.W.; Jiang, Z.; Collier, I.D.; Blakli, H.; Rosair, G.M.; Bailey, P.D.; Morgan, K.M.; Kohno, Y.; Adams, D.R. Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones. Org. Biomol. Chem.,  2008, 6(1), 175-186.
 [http://dx.doi.org/10.1039/B713638B] [PMID:  18075664]

[12]
Tang, J.; Wang, B.; Wu, T.; Wan, J.; Tu, Z.; Njire, M.; Wan, B.; Franzblauc, S.G.; Zhang, T.; Lu, X.; Ding, K. Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5- a]pyridine-3-carboxamides as Novel Antitubercular Agents. ACS Med. Chem. Lett.,  2015, 6(7), 814-818.
 [http://dx.doi.org/10.1021/acsmedchemlett.5b00176] [PMID:  26191372]

[13]
Wang, A.; Liu, Y.Z.; Shen, Z.; Qiao, Z.; Ma, X. Regioselective Synthesis of Pyrazolo[1,5- a]pyridine via TEMPO-Mediated [3 + 2] Annulation–Aromatization of N -Aminopyridines and α,β-Unsaturated Compounds. Org. Lett.,  2022, 24(7), 1454-1459.
 [http://dx.doi.org/10.1021/acs.orglett.2c00035] [PMID:  35166547]

[14]
Devi Priya, D.; Nandhakumar, M.; Mohana Roopan, S. Pyrazolo[1,5- a]pyridine: Recent synthetic view on crucial heterocycles. Synth. Commun.,  2020, 50(23), 3535-3562.
 [http://dx.doi.org/10.1080/00397911.2020.1805468]

[15]
Wu, H.C.; Hwang, L.C.; Wu, M.J. A copper-mediated cyclization reaction of hydrazine with enediynones providing pyrazolo[1,5-a]pyridines. Org. Biomol. Chem.,  2011, 9(3), 670-672.
 [http://dx.doi.org/10.1039/C0OB00756K] [PMID:  21120244]

[16]
Wu, H.C.; Yang, C.W.; Hwang, L.C.; Au Wu, M.J. (i)-catalyzed and iodine-mediated cyclization of enynylpyrazoles to provide pyrazolo[1,5-a]pyridines. Org. Biomol. Chem.,  2012, 10(33), 6640-6648.
 [http://dx.doi.org/10.1039/c2ob25973g] [PMID:  22825562]

[17]
Mousseau, J.J.; Fortier, A.; Charette, A.B. Synthesis of 2-substituted pyrazolo[1,5-a]pyridines through cascade direct alkenylation/cyclization reactions. Org. Lett.,  2010, 12(3), 516-519.
 [http://dx.doi.org/10.1021/ol902710f] [PMID:  20052989]

[18]
Mousseau, J.J.; Bull, J.A.; Ladd, C.L.; Fortier, A.; Sustac Roman, D.; Charette, A.B. Synthesis of 2- and 2,3-substituted pyrazolo[1,5-a]pyridines: Scope and mechanistic considerations of a domino direct alkynylation and cyclization of N-iminopyridinium ylides using alkenyl bromides, alkenyl iodides, and alkynes. J. Org. Chem.,  2011, 76(20), 8243-8261.
 [http://dx.doi.org/10.1021/jo201303x] [PMID:  21902233]

[19]
Ling, L.; Chen, J.; Song, J.; Zhang, Y.; Li, X.; Song, L.; Shi, F.; Li, Y.; Wu, C. From N-benzoylpyridinium imides to pyrazolo[1,5-a]pyridines: A mechanistic discussion on a stoichiometric Cu protocol. Org. Biomol. Chem.,  2013, 11(23), 3894-3902.
 [http://dx.doi.org/10.1039/c3ob40448j] [PMID:  23657368]

[20]
Ding, S.; Yan, Y.; Jiao, N. Copper-catalyzed direct oxidative annulation of N-iminopyridinium ylides with terminal alkynes using O 2 as oxidant. Chem. Commun. (Camb.),  2013, 49(39), 4250-4252.
 [http://dx.doi.org/10.1039/C2CC33706A] [PMID:  22790323]

[21]
Jannapu Reddy, R.; Sharadha, N.; Haritha Kumari, A. Base-mediated [3 + 2]-cycloannulation strategy for the synthesis of pyrazolo[1,5- a]pyridine derivatives using (E)-β-iodovinyl sulfones. Org. Biomol. Chem.,  2022, 20(21), 4331-4337.
 [http://dx.doi.org/10.1039/D2OB00499B] [PMID:  35451451]

[22]
Mennie, K.M.; Reutershan, M.H.; White, C.; Adams, B.; Becker, B.; Deng, J.; Katz, J.D.; LaBlue, E.; Margrey, K.; Saurí, J. Divergent and Regioselective Synthesis of Pyrazolo[1,5- a]pyridines and Imidazo[1,5- a]pyridines. Org. Lett.,  2021, 23(12), 4694-4698.
 [http://dx.doi.org/10.1021/acs.orglett.1c01431] [PMID:  34037404]

[23]
Mohan, D.C.; Ravi, C.; Rao, S.N.; Adimurthy, S. Copper-mediated synthesis of pyrazolo[1,5-a]pyridines through oxidative linkage of C–C/N–N bonds. Org. Biomol. Chem.,  2015, 13(12), 3556-3560.
 [http://dx.doi.org/10.1039/C5OB00018A] [PMID:  25679457]

[24]
Ibrahim, H.M.; Behbehani, H.; Mostafa, N.S. Scalable Sonochemical Synthetic Strategy for Pyrazolo[1,5- a]pyridine Derivatives: First Catalyst-Free Concerted [3 + 2] Cycloaddition of Alkyne and Alkene Derivatives to 2-Imino-1 H -pyridin-1-amines. ACS Omega,  2019, 4(4), 7182-7193.
 [http://dx.doi.org/10.1021/acsomega.9b00562] [PMID:  31459824]

[25]
Motornov, V.A.; Tabolin, A.A.; Nelyubina, Y.V.; Nenajdenko, V.G.; Ioffe, S.L. Copper-mediated oxidative [3 + 2]-annulation of nitroalkenes and pyridinium imines: Efficient synthesis of 3-fluoro- and 3-nitro-pyrazolo[1,5- a]pyridines. Org. Biomol. Chem.,  2020, 18(7), 1436-1448.

[26]
Vorob’ev, A.Y.; Supranovich, V.I.; Borodkin, G.I.; Shubin, V.G. New approach toward the synthesis of deuterated pyrazolo[1,5- a]pyridines and 1,2,4-triazolo[1,5- a]pyridines. Beilstein J. Org. Chem.,  2017, 13, 800-805.
 [http://dx.doi.org/10.3762/bjoc.13.80] [PMID:  28546837] [http://dx.doi.org/10.1039/C9OB02668A] [PMID:  32022079]

[27]
Lopes, S.M.M.; Correia, C.F.O.; Nunes, S.C.C.; Pereira, N.A.M.; Ferreira, A.R.F.; Sousa, E.P.; Gomes, C.S.B.; Salvador, J.A.R.; Pais, A.A.C.C.; Pinho e Melo, T.M.V.D. Synthesis of chiral hexacyclic steroids via [8π + 2π] cycloaddition of diazafulvenium methides. Org. Biomol. Chem.,  2015, 13(34), 9127-9139.
 [http://dx.doi.org/10.1039/C5OB01110H] [PMID:  26223980]

[28]
Lopes, S.M.M.; Sousa, E.P.; Barreira, L.; Marques, C.; Rodrigues, M.J.; Pinho e Melo, T.M.V.D. Synthesis and anti-cancer activity of chiral tetrahydropyrazolo[1,5- a]pyridine-fused steroids. Steroids,  2017, 122, 16-23.
 [http://dx.doi.org/10.1016/j.steroids.2017.03.006] [PMID:  28342744]

[29]
Ravi, C.; Qayum, A.; Chandra Mohan, D.; Singh, S.K.; Adimurthy, S. Design, synthesis and cytotoxicity studies of novel pyrazolo[1, 5-a]pyridine derivatives. Eur. J. Med. Chem.,  2017, 126, 277-285.
 [http://dx.doi.org/10.1016/j.ejmech.2016.11.037] [PMID:  27889631]

[30]
Jorda, R.; Lopes, S.M.M.; Řezníčková, E.; Ajani, H.; Pereira, A.V.; Gomes, C.S.B. M V D Pinho E Melo, T.; Tetrahydropyrazolo, T. Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer. Eur. J. Med. Chem.,  2019, 178, 168-176.
 [http://dx.doi.org/10.1016/j.ejmech.2019.05.064] [PMID:  31181481]

[31]
Tanaka, Y.; Aikawa, K.; Nishida, G.; Homma, M.; Sogabe, S.; Igaki, S.; Hayano, Y.; Sameshima, T.; Miyahisa, I.; Kawamoto, T.; Tawada, M.; Imai, Y.; Inazuka, M.; Cho, N.; Imaeda, Y.; Ishikawa, T. Discovery of potent Mcl-1/Bcl-xL dual inhibitors by using a hybridization strategy based on structural analysis of target proteins. J. Med. Chem.,  2013, 56(23), 9635-9645.
 [http://dx.doi.org/10.1021/jm401170c] [PMID:  24215352]

[32]
Sainas, S.; Pippione, A.C.; Lupino, E.; Giorgis, M.; Circosta, P.; Gaidano, V.; Goyal, P.; Bonanni, D.; Rolando, B.; Cignetti, A.; Ducime, A.; Andersson, M.; Järvå, M.; Friemann, R.; Piccinini, M.; Ramondetti, C.; Buccinnà, B.; Al-Karadaghi, S.; Boschi, D.; Saglio, G.; Lolli, M.L. Targeting Myeloid Differentiation Using Potent 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold-Based Human Dihydroorotate Dehydrogenase Inhibitors. J. Med. Chem.,  2018, 61(14), 6034-6055.
 [http://dx.doi.org/10.1021/acs.jmedchem.8b00373] [PMID:  29939742]

[33]
Sainas, S.; Giorgis, M.; Circosta, P.; Gaidano, V.; Bonanni, D.; Pippione, A.C.; Bagnati, R.; Passoni, A.; Qiu, Y.; Cojocaru, C.F.; Canepa, B.; Bona, A.; Rolando, B.; Mishina, M.; Ramondetti, C.; Buccinnà, B.; Piccinini, M.; Houshmand, M.; Cignetti, A.; Giraudo, E.; Al-Karadaghi, S.; Boschi, D.; Saglio, G.; Lolli, M.L. Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold: SAR of the Biphenyl Moiety. J. Med. Chem.,  2021, 64(9), 5404-5428.
 [http://dx.doi.org/10.1021/acs.jmedchem.0c01549] [PMID:  33844533]

[34]
Lu, X.; Tang, J.; Cui, S.; Wan, B.; Franzblauc, S.G.; Zhang, T.; Zhang, X.; Ding, K. Pyrazolo[1,5-a]pyridine-3-carboxamide hybrids: Design, synthesis and evaluation of anti-tubercular activity. Eur. J. Med. Chem.,  2017, 125, 41-48.
 [http://dx.doi.org/10.1016/j.ejmech.2016.09.030] [PMID:  27654393]

[35]
Hu, X.; Wan, B.; Liu, Y.; Shen, J.; Franzblau, S.G.; Zhang, T.; Ding, K.; Lu, X. Identification of Pyrazolo[1,5- a]pyridine-3-carboxamide Diaryl Derivatives as Drug Resistant Antituberculosis Agents. ACS Med. Chem. Lett.,  2019, 10(3), 295-299.
 [http://dx.doi.org/10.1021/acsmedchemlett.8b00410] [PMID:  30891129]

[36]
Lu, X.; Williams, Z.; Hards, K.; Tang, J.; Cheung, C.Y.; Aung, H.L.; Wang, B.; Liu, Z.; Hu, X.; Lenaerts, A.; Woolhiser, L.; Hastings, C.; Zhang, X.; Wang, Z.; Rhee, K.; Ding, K.; Zhang, T.; Cook, G.M. Pyrazolo[1,5-a]pyridine Inhibitor of the Respiratory Cytochrome bcc Complex for the Treatment of Drug-resistant Tuberculosis. ACS Infect. Dis.,  2019, 5(2), 239-249.
 [http://dx.doi.org/10.1021/acsinfecdis.8b00225] [PMID:  30485737]

[37]
Johns, B.A.; Gudmundsson, K.S.; Turner, E.M.; Allen, S.H.; Jung, D.K.; Sexton, C.J.; Boyd, F.L., Jr; Peel, M.R. Pyrazolo[1,5-a]pyridines: Synthetic approaches to a novel class of antiherpetics. Tetrahedron,  2003, 59(45), 9001-9011.
 [http://dx.doi.org/10.1016/j.tet.2003.02.003]

[38]
Johns, B.A.; Gudmundsson, K.S.; Turner, E.M.; Allen, S.H.; Samano, V.A.; Ray, J.A.; Freeman, G.A.; Boyd, F.L., Jr; Sexton, C.J.; Selleseth, D.W.; Creech, K.L.; Moniri, K.R. Pyrazolopyridine antiherpetics: SAR of C2′ and C7 amine substituents. Bioorg. Med. Chem.,  2005, 13(7), 2397-2411.
 [http://dx.doi.org/10.1016/j.bmc.2005.01.044] [PMID:  15755642]

[39]
Allen, S.H.; Johns, B.A.; Gudmundsson, K.S.; Freeman, G.A.; Boyd, F.L., Jr; Sexton, C.H.; Selleseth, D.W.; Creech, K.L.; Moniri, K.R. Synthesis of C-6 substituted pyrazolo[1,5-a]pyridines with potent activity against herpesviruses. Bioorg. Med. Chem.,  2006, 14(4), 944-954.
 [http://dx.doi.org/10.1016/j.bmc.2005.09.015] [PMID:  16213142]

[40]
Johns, B.A.; Gudmundsson, K.S.; Allen, S.H. Pyrazolo[1,5-a]pyridine antiherpetics: Effects of the C3 substituent on antiviral activity. Bioorg. Med. Chem. Lett.,  2007, 17(10), 2858-2862.
 [http://dx.doi.org/10.1016/j.bmcl.2007.02.058] [PMID:  17350256]

[41]
Tai, V.W.F.; Garrido, D.; Price, D.J.; Maynard, A.; Pouliot, J.J.; Xiong, Z.; Seal, J.W., III; Creech, K.L.; Kryn, L.H.; Baughman, T.M.; Peat, A.J. Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein. Bioorg. Med. Chem. Lett.,  2014, 24(10), 2288-2294.
 [http://dx.doi.org/10.1016/j.bmcl.2014.03.080] [PMID:  24731273]

[42]
Umei, K.; Nishigaya, Y.; Kondo, A.; Tatani, K.; Tanaka, N.; Kohno, Y.; Seto, S. Novel pyrazolo[1,5- a]pyridines as orally active EP 1 receptor antagonists: Synthesis, structure-activity relationship studies, and biological evaluation. Bioorg. Med. Chem.,  2017, 25(9), 2635-2642.
 [http://dx.doi.org/10.1016/j.bmc.2017.03.003] [PMID:  28342692]

[43]
Nishigaya, Y.; Umei, K.; Saito, Y.; Watanabe, H.; Kondo, T.; Kondo, A.; Kawamura, N.; Tatani, K.; Kohno, Y.; Tanaka, N.; Seto, S. Discovery of novel pyrazolo[1,5-a]pyridine-based EP1 receptor antagonists by scaffold hopping: Design, synthesis, and structure-activity relationships. Bioorg. Med. Chem. Lett.,  2017, 27(17), 4044-4050.
 [http://dx.doi.org/10.1016/j.bmcl.2017.07.055] [PMID:  28784294]

[44]
Taguchi, R.; Shikata, K.; Furuya, Y.; Ino, M.; Shin, K.; Shibata, H. Selective corticotropin-releasing factor 1 receptor antagonist E2508 has potent antidepressant-like and anxiolytic-like properties in rodent models. Behav. Brain Res.,  2016, 312, 138-147.
 [http://dx.doi.org/10.1016/j.bbr.2016.06.017] [PMID:  27297028]

[45]
Boeckler, F.; Leng, A.; Mura, A.; Bettinetti, L.; Feldon, J.; Gmeiner, P.; Ferger, B. Attenuation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity by the novel selective dopamine D3-receptor partial agonist FAUC 329 predominantly in the nucleus accumbens of mice. Biochem. Pharmacol.,  2003, 66(6), 1025-1032.
 [http://dx.doi.org/10.1016/S0006-2952(03)00451-9] [PMID:  12963489]

[46]
Prante, O.; Tietze, R.; Hocke, C.; Löber, S.; Hübner, H.; Kuwert, T.; Gmeiner, P. Synthesis, radiofluorination, and in vitro evaluation of pyrazolo[1,5-a]pyridine-based dopamine D4 receptor ligands: Discovery of an inverse agonist radioligand for PET. J. Med. Chem.,  2008, 51(6), 1800-1810.
 [http://dx.doi.org/10.1021/jm701375u] [PMID:  18307287]

[47]
Möller, D.; Kling, R.C.; Skultety, M.; Leuner, K.; Hübner, H.; Gmeiner, P. Functionally selective dopamine D2, D3 receptor partial agonists. J. Med. Chem.,  2014, 57(11), 4861-4875.
 [http://dx.doi.org/10.1021/jm5004039] [PMID:  24831693]

[48]
Möller, D.; Banerjee, A.; Uzuneser, T.C.; Skultety, M.; Huth, T.; Plouffe, B.; Hübner, H.; Alzheimer, C.; Friedland, K.; Müller, C.P.; Bouvier, M.; Gmeiner, P. Discovery of G Protein-Biased Dopaminergics with a Pyrazolo[1,5- a]pyridine Substructure. J. Med. Chem.,  2017, 60(7), 2908-2929.
 [http://dx.doi.org/10.1021/acs.jmedchem.6b01857] [PMID:  28248104]

[49]
Männel, B.; Hübner, H.; Möller, D.; Gmeiner, P. β-Arrestin biased dopamine D2 receptor partial agonists: Synthesis and pharmacological evaluation. Bioorg. Med. Chem.,  2017, 25(20), 5613-5628.
 [http://dx.doi.org/10.1016/j.bmc.2017.08.037] [PMID:  28870802]

[50]
Cheung, M.; Harris, P.A.; Badiang, J.G.; Peckham, G.E.; Chamberlain, S.D.; Alberti, M.J.; Jung, D.K.; Harris, S.S.; Bramson, N.H.; Epperly, A.H.; Stimpson, S.A.; Peel, M.R. The identification of pyrazolo[1,5-a]pyridines as potent p38 kinase inhibitors. Bioorg. Med. Chem. Lett.,  2008, 18(20), 5428-5430.
 [http://dx.doi.org/10.1016/j.bmcl.2008.09.040] [PMID:  18818075]

[51]
Kendall, J.D.; Giddens, A.C.; Tsang, K.Y.; Frédérick, R.; Marshall, E.S.; Singh, R.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Chao, M.; Malik, A.; Yu, S.; Chaussade, C.; Buchanan, C.; Rewcastle, G.W.; Baguley, B.C.; Flanagan, J.U.; Jamieson, S.M.F.; Denny, W.A.; Shepherd, P.R. Novel pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors: Exploring the benzenesulfonohydrazide SAR. Bioorg. Med. Chem.,  2012, 20(1), 58-68.
 [http://dx.doi.org/10.1016/j.bmc.2011.11.031] [PMID:  22177407]

[52]
Kendall, J.D.; Giddens, A.C.; Tsang, K.Y.; Marshall, E.S.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Chao, M.; Malik, A.; Yu, S.; Chaussade, C.; Buchanan, C.; Jamieson, S.M.F.; Rewcastle, G.W.; Baguley, B.C.; Denny, W.A.; Shepherd, P.R. Novel pyrazolo[1,5- a]pyridines with improved aqueous solubility as p110α-selective PI3 kinase inhibitors. Bioorg. Med. Chem. Lett.,  2017, 27(2), 187-190.
 [http://dx.doi.org/10.1016/j.bmcl.2016.11.078] [PMID:  27923617]

[53]
Al-Nema, M.; Gaurav, A.; Lee, M.T.; Okechukwu, P.; Nimmanpipug, P.; Lee, V.S. Evaluation of the acute oral toxicity and antipsychotic activity of a dual inhibitor of PDE1B and PDE10A in rat model of schizophrenia. PLoS One,  2022, 17(12), e0278216.
 [http://dx.doi.org/10.1371/journal.pone.0278216] [PMID:  36454774]

[54]
Al-Nema, M.; Gaurav, A.; Lee, V.S. Docking based screening and molecular dynamics simulations to identify potential selective PDE4B inhibitor. Heliyon,  2020, 6(9), e04856.
 [http://dx.doi.org/10.1016/j.heliyon.2020.e04856] [PMID:  32984588]

[55]
Al-Nema, M.; Gaurav, A.; Lee, V.S.; Gunasekaran, B.; Lee, M.T.; Okechukwu, P. Identification of dual inhibitor of phosphodiesterase 1B/10A using structure-based drug design approach. J. Mol. Liq.,  2021, 342, 117485.
 [http://dx.doi.org/10.1016/j.molliq.2021.117485]

[56]
Al-Nema, M.; Gaurav, A.; Lee, V.S.; Gunasekaran, B.; Lee, M.T.; Okechukwu, P.; Nimmanpipug, P. Structure-based discovery and bio-evaluation of a cyclopenta[4,5]thieno[2,3- d]pyrimidin-4-one as a phosphodiesterase 10A inhibitor. RSC Advances,  2022, 12(3), 1576-1591.
 [http://dx.doi.org/10.1039/D1RA07649C] [PMID:  35425186]

[57]
Por, C.S.; Akowuah, G.A.; Gaurav, A. Quantitative Structure–Activity Relationship Modeling of s-Triazines and 2-Arylpyrimidines as Selective PDE4B Inhibitors. Thaiphesatchasan,  2018, 42, 69-83.

[58]
Ochiai, K.; Ando, N.; Iwase, K.; Kishi, T.; Fukuchi, K.; Ohinata, A.; Zushi, H.; Yasue, T.; Adams, D.R.; Kohno, Y. Phosphodiesterase inhibitors. Part 2: Design, synthesis, and structure–activity relationships of dual PDE3/4-inhibitory pyrazolo[1,5-a]pyridines with anti-inflammatory and bronchodilatory activity. Bioorg. Med. Chem. Lett.,  2011, 21(18), 5451-5456.
 [http://dx.doi.org/10.1016/j.bmcl.2011.06.118] [PMID:  21764304]

[59]
Kojima, A.; Takita, S.; Sumiya, T.; Ochiai, K.; Iwase, K.; Kishi, T.; Ohinata, A.; Yageta, Y.; Yasue, T.; Kohno, Y. Phosphodiesterase inhibitors. Part 6: Design, synthesis, and structure–activity relationships of PDE4-inhibitory pyrazolo[1,5-a]pyridines with anti-inflammatory activity. Bioorg. Med. Chem. Lett.,  2013, 23(19), 5311-5316.
 [http://dx.doi.org/10.1016/j.bmcl.2013.07.069] [PMID:  23988356]

[60]
Koike, T.; Takai, T.; Hoashi, Y.; Nakayama, M.; Kosugi, Y.; Nakashima, M.; Yoshikubo, S.; Hirai, K.; Uchikawa, O. Synthesis of a novel series of tricyclic dihydrofuran derivatives: Discovery of 8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridines as melatonin receptor (MT1/MT2) ligands. J. Med. Chem.,  2011, 54(12), 4207-4218.
 [http://dx.doi.org/10.1021/jm200385u] [PMID:  21568291]

[61]
Preston, S.; Jabbar, A.; Nowell, C.; Joachim, A.; Ruttkowski, B.; Baell, J.; Cardno, T.; Korhonen, P.K.; Piedrafita, D.; Ansell, B.R.E.; Jex, A.R.; Hofmann, A.; Gasser, R.B. Low cost whole-organism screening of compounds for anthelmintic activity. Int. J. Parasitol.,  2015, 45(5), 333-343.
 [http://dx.doi.org/10.1016/j.ijpara.2015.01.007] [PMID:  25746136]

[62]
Ohori, M.; Takeuchi, M.; Maruki, R.; Nakajima, H.; Miyake, H. FR180204, a novel and selective inhibitor of extracellular signal-regulated kinase, ameliorates collagen-induced arthritis in mice. Naunyn Schmiedebergs Arch. Pharmacol.,  2007, 374(4), 311-316.
 [http://dx.doi.org/10.1007/s00210-006-0117-7] [PMID:  17123065]

[63]
Bettinetti, L.; Hübner, H.; Gmeiner, P. Chirospecific and subtype selective dopamine receptor binding of heterocyclic methoxynaphthamide analogs. Arch. Pharm. (Weinheim),  2005, 338(5-6), 276-280.
 [http://dx.doi.org/10.1002/ardp.200400997] [PMID:  15952242]

[64]
Boeckler, F.; Russig, H.; Zhang, W.; Löber, S.; Schetz, J.; Hübner, H.; Ferger, B.; Gmeiner, P.; Feldon, J. FAUC 213, a highly selective dopamine D4 receptor full antagonist, exhibits atypical antipsychotic properties in behavioural and neurochemical models of schizophrenia. Psychopharmacology (Berl.),  2004, 175(1), 7-17.
 [http://dx.doi.org/10.1007/s00213-004-1782-1] [PMID:  15007532]

[65]
Liu, Y.; Gao, Y.; Liu, J.; Tan, Y.; Liu, Z.; Chhotaray, C.; Jiang, H.; Lu, Z.; Chiwala, G.; Wang, S.; Makafe, G.; Islam, M.M.; Hameed, H.M.A.; Cai, X.; Wang, C.; Li, X.; Tan, S.; Zhang, T. The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model. Nat. Commun.,  2019, 10(1), 524.
 [http://dx.doi.org/10.1038/s41467-019-08464-y] [PMID:  30705268]
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DOI https://dx.doi.org/10.2174/1570180820666230803101948	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X
Letters in Drug Design & Discovery

Synthetic and Pharmacological Expedition of Pyrazolo[1,5-a]pyridine: A Comprehensive Review

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