(R)-N-((1R,3r,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(4-chlorophenyl)-2-(2-(4-chlorophenyl)acetamido)propanamide | 1310687-95-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-N-((1R,3r,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(4-chlorophenyl)-2-(2-(4-chlorophenyl)acetamido)propanamide
• CAS: 1310687-95-6
• 化学式: C₂₄H₂₇Cl₂N₃O₂
• 分子量: 460.403
• InChiKey: VYUFUXRLJDFDIC-CLAROIROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.66
• 重原子数：
  31.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  70.23
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (1S,5R)-8-Methyl-8-azabicyclo[3.2.1]octan-3-amine 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-N-((1R,3r,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(4-chlorophenyl)-2-(2-(4-chlorophenyl)acetamido)propanamide
  参考文献：
  名称：

  The discovery of novel 8-azabicyclo[3.2.1]octan-3-yl)-3-(4-chlorophenyl) propanamides as vasopressin V1A receptor antagonists

  摘要：

  The discovery of a novel series of 8-azabicyclo[3.2.1] octan-3-yl)-3-(4-chlorophenyl) propanamide antagonists of the vasopressin V-1A receptor is disclosed. Compounds 47 and 48 were found to be high affinity, selective vasopressin V-1A antagonists. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.096

文献信息

• Optimisation of pharmacokinetic properties to afford an orally bioavailable and selective V1A receptor antagonist
  作者：William Arbuckle、James Baker、David Barn、Matilda Bingham、Angus Brown、Kirsteen Buchanan、Mark Craighead、Richard Goodwin、Susan Goutcher、Michael Kiczun、Amanda Lyons、Rachel Milne、Brian Montgomery、Susan Napier、Jeremy Presland、Hazel Sloan、Zara Turnbull、Grant Wishart

  DOI：10.1016/j.bmcl.2011.05.092

  日期：2011.8

  The previously described lead compound 5 is a potent and selective V1A antagonist with affinity at both the rat and human receptor, but displays poor oral bioavailability and moderate clearance. We report herein the successful optimisation of the pharmacokinetic (PK) properties to afford the potent, selective, orally bioavailable and CNS penetrant compound 15f. A custom optimisation approach was required which demonstrated the value of using early, rapid in vivo PK studies to show improvements in oral exposure. Such assays may be of particular value where low oral bioavailability is anticipated to be multifactorial (e.g., permeability, gut wall metabolism and/or transport) where satisfactory modelling of in vitro data is likely to be difficult within a drug discovery context. (C) 2011 Published by Elsevier Ltd.
• The discovery of novel 8-azabicyclo[3.2.1]octan-3-yl)-3-(4-chlorophenyl) propanamides as vasopressin V1A receptor antagonists
  作者：Susan Napier、Grant Wishart、William Arbuckle、James Baker、David Barn、Matilda Bingham、Angus Brown、Alan Byford、Chris Claxton、Mark Craighead、Kirsteen Buchanan、Lee Fielding、Lindsay Gibson、Richard Goodwin、Susan Goutcher、Nicholas Irving、Cliona MacSweeney、Rachel Milne、Chris Mort、Jeremy Presland、Hazel Sloan、Fiona Thomson、Zara Turnbull、Trevor Young

  DOI：10.1016/j.bmcl.2011.02.096

  日期：2011.5

  The discovery of a novel series of 8-azabicyclo[3.2.1] octan-3-yl)-3-(4-chlorophenyl) propanamide antagonists of the vasopressin V-1A receptor is disclosed. Compounds 47 and 48 were found to be high affinity, selective vasopressin V-1A antagonists. (C) 2011 Elsevier Ltd. All rights reserved.