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Identification of 1-{2-[4-chloro-1'-(2,2-dimethylpropyl)-7-hydroxy-1,2-dihydrospiro[indole-3,4'-piperidine]-1-yl]phenyl}-3-{5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl}urea, a potent, efficacious and orally bioavailable P2Y(1) antagonist as an antiplatelet agent.
Jeon YT, Yang W, Qiao JX, Li L, Ruel R, Thibeault C, Hiebert S, Wang TC, Wang Y, Liu Y, Clark CG, Wong HS, Zhu J, Wu DR, Sun D, Chen BC, Mathur A, Chacko SA, Malley M, Chen XQ, Shen H, Huang CS, Schumacher WA, Bostwick JS, Stewart AB, Price LA, Hua J, Li D, Levesque PC, Seiffert DA, Rehfuss R, Wexler RR, Lam PY. Jeon YT, et al. Among authors: wang tc, wang y. Bioorg Med Chem Lett. 2014 Mar 1;24(5):1294-8. doi: 10.1016/j.bmcl.2014.01.066. Epub 2014 Jan 31. Bioorg Med Chem Lett. 2014. PMID: 24513044
Macrocyclic inhibitors of Factor XIa: Discovery of alkyl-substituted macrocyclic amide linkers with improved potency.
Corte JR, Yang W, Fang T, Wang Y, Osuna H, Lai A, Ewing WR, Rossi KA, Myers JE Jr, Sheriff S, Lou Z, Zheng JJ, Harper TW, Bozarth JM, Wu Y, Luettgen JM, Seiffert DA, Quan ML, Wexler RR, Lam PYS. Corte JR, et al. Among authors: wang y. Bioorg Med Chem Lett. 2017 Aug 15;27(16):3833-3839. doi: 10.1016/j.bmcl.2017.06.058. Epub 2017 Jun 23. Bioorg Med Chem Lett. 2017. PMID: 28687203
Structure based design of macrocyclic factor XIa inhibitors: Discovery of cyclic P1 linker moieties with improved oral bioavailability.
Clark CG, Rossi KA, Corte JR, Fang T, Smallheer JM, De Lucca I, Nirschl DS, Orwat MJ, Pinto DJP, Hu Z, Wang Y, Yang W, Jeon Y, Ewing WR, Myers JE Jr, Sheriff S, Lou Z, Bozarth JM, Wu Y, Rendina A, Harper T, Zheng J, Xin B, Xiang Q, Luettgen JM, Seiffert DA, Wexler RR, Lam PYS. Clark CG, et al. Among authors: wang y. Bioorg Med Chem Lett. 2019 Oct 1;29(19):126604. doi: 10.1016/j.bmcl.2019.08.008. Epub 2019 Aug 16. Bioorg Med Chem Lett. 2019. PMID: 31445854
Potent, Orally Bioavailable, and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups.
Corte JR, Pinto DJP, Fang T, Osuna H, Yang W, Wang Y, Lai A, Clark CG, Sun JH, Rampulla R, Mathur A, Kaspady M, Neithnadka PR, Li YC, Rossi KA, Myers JE Jr, Sheriff S, Lou Z, Harper TW, Huang C, Zheng JJ, Bozarth JM, Wu Y, Wong PC, Crain EJ, Seiffert DA, Luettgen JM, Lam PYS, Wexler RR, Ewing WR. Corte JR, et al. Among authors: wang y. J Med Chem. 2020 Jan 23;63(2):784-803. doi: 10.1021/acs.jmedchem.9b01768. Epub 2020 Jan 2. J Med Chem. 2020. PMID: 31833761
Discovery of a High Affinity, Orally Bioavailable Macrocyclic FXIa Inhibitor with Antithrombotic Activity in Preclinical Species.
Yang W, Wang Y, Lai A, Clark CG, Corte JR, Fang T, Gilligan PJ, Jeon Y, Pabbisetty KB, Rampulla RA, Mathur A, Kaspady M, Neithnadka PR, Arumugam A, Raju S, Rossi KA, Myers JE Jr, Sheriff S, Lou Z, Zheng JJ, Chacko SA, Bozarth JM, Wu Y, Crain EJ, Wong PC, Seiffert DA, Luettgen JM, Lam PYS, Wexler RR, Ewing WR. Yang W, et al. Among authors: wang y. J Med Chem. 2020 Jul 9;63(13):7226-7242. doi: 10.1021/acs.jmedchem.0c00464. Epub 2020 Jun 17. J Med Chem. 2020. PMID: 32456431
Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy.
Dilger AK, Pabbisetty KB, Corte JR, De Lucca I, Fang T, Yang W, Pinto DJP, Wang Y, Zhu Y, Mathur A, Li J, Hou X, Smith D, Sun D, Zhang H, Krishnananthan S, Wu DR, Myers JE Jr, Sheriff S, Rossi KA, Chacko S, Zheng JJ, Galella MA, Ziemba T, Dierks EA, Bozarth JM, Wu Y, Crain E, Wong PC, Luettgen JM, Wexler RR, Ewing WR. Dilger AK, et al. Among authors: wang y. J Med Chem. 2022 Feb 10;65(3):1770-1785. doi: 10.1021/acs.jmedchem.1c00613. Epub 2021 Sep 8. J Med Chem. 2022. PMID: 34494428
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