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(2R,4R)-N-(4-氯苯基)-N-(2-氟-4-(2-氧代吡啶-1(2H)-基)苯基)-4-甲氧基吡咯烷-1,2-二甲酰胺（PD 0348292）的发现，一种口服有效的Xa因子抑制剂。

The discovery of (2R,4R)-N-(4-chlorophenyl)-N- (2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidine-1,2-dicarboxamide (PD 0348292), an orally efficacious factor Xa inhibitor.

作者信息

Kohrt Jeffrey T, Bigge Christopher F, Bryant John W, Casimiro-Garcia Agustin, Chi Liguo, Cody Wayne L, Dahring Tawny, Dudley Danette A, Filipski Kevin J, Haarer Staci, Heemstra Ron, Janiczek Nancy, Narasimhan Lakshmi, McClanahan Thomas, Peterson J Thomas, Sahasrabudhe Vaisheli, Schaum Robert, Van Huis Chad A, Welch Kathleen M, Zhang Erli, Leadley Robert J, Edmunds Jeremy J

机构信息

Michigan Laboratories, Ann Arbor Campus, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.

出版信息

Chem Biol Drug Des. 2007 Aug;70(2):100-12. doi: 10.1111/j.1747-0285.2007.00539.x.

DOI:10.1111/j.1747-0285.2007.00539.x
PMID:17683371
Abstract

Herein, we report the discovery of novel, proline-based factor Xa inhibitors containing a neutral P1 chlorophenyl pharmacophore. Through the additional incorporation of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one 22, as a P4 pharmacophore, we discovered compound 7 (PD 0348292). This compound is a selective, orally bioavailable, efficacious FXa inhibitor that is currently in phase II clinical trials for the treatment and prevention of thrombotic disorders.

摘要

在此，我们报告了含有中性P1氯苯基药效团的新型脯氨酸基凝血因子Xa抑制剂的发现。通过额外引入1-(4-氨基-3-氟苯基)-1H-吡啶-2-酮22作为P4药效团，我们发现了化合物7（PD 0348292）。该化合物是一种选择性、口服生物可利用、有效的凝血因子Xa抑制剂，目前正处于治疗和预防血栓性疾病的II期临床试验阶段。

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