[(1S,3R)-3-amino-1-propan-2-ylcyclopentyl]-[4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methanone | 872673-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: [(1S,3R)-3-amino-1-propan-2-ylcyclopentyl]-[4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methanone
• CAS: 872673-23-9
• 化学式: C₁₉H₂₇F₃N₄O
• 分子量: 384.445
• InChiKey: FBEOHPLXMTVACP-KDOFPFPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-甲氧基-四氢-2H-吡喃-4-酮 、 [(1S,3R)-3-amino-1-propan-2-ylcyclopentyl]-[4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methanone 在 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 、 ((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(6-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)methanone
  参考文献：
  名称：

  Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist

  摘要：

  We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.015
• 作为产物：
  描述：

  (1S,3R)-3-((tert-butoxycarbonyl)amino)-1-isopropylcyclopentane-1-carboxylic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 [(1S,3R)-3-amino-1-propan-2-ylcyclopentyl]-[4-[6-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methanone
  参考文献：
  名称：

  Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist

  摘要：

  We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.015

文献信息

• 3-AMINOCYCLOPENTANECARBOXAMIDES AS MODULATORS OF CHEMOKINE RECEPTORS
  申请人：Xue Chu-Biao

  公开号：US20100119503A1

  公开（公告）日：2010-05-13

  The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及式I的化合物：它们是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性有关的疾病方面是有用的。
• US7449467B2
  申请人：——

  公开号：US7449467B2

  公开（公告）日：2008-11-11
• US7618970B2
  申请人：——

  公开号：US7618970B2

  公开（公告）日：2009-11-17
• US8563582B2
  申请人：——

  公开号：US8563582B2

  公开（公告）日：2013-10-22
• Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist
  作者：Changsheng Zheng、Ganfeng Cao、Michael Xia、Hao Feng、Joseph Glenn、Rajan Anand、Ke Zhang、Taisheng Huang、Anlai Wang、Ling Kong、Mei Li、Laurine Galya、Robert O. Hughes、Rajesh Devraj、Phillip A. Morton、D. Joseph Rogier、Maryanne Covington、Fred Baribaud、Niu Shin、Peggy Scherle、Sharon Diamond、Swamy Yeleswaram、Kris Vaddi、Robert Newton、Greg Hollis、Steven Friedman、Brian Metcalf、Chu-Biao Xue

  DOI：10.1016/j.bmcl.2011.01.015

  日期：2011.3

  We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate. (C) 2011 Elsevier Ltd. All rights reserved.