N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)cyclopentanecarboxamide | 946584-97-0

• 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: N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)cyclopentanecarboxamide
• 英文别名: N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]cyclopentanecarboxamide
• CAS: 946584-97-0
• 化学式: C₂₄H₃₅ClN₂O₃
• 分子量: 435.007
• InChiKey: UTGYFIZUYRNNRM-YKSBVNFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)cyclopentanecarboxamide 、 二乙胺基三氟化硫 以 二氯甲烷 为溶剂， 反应 16.0h， 以Example 616 was isolated as a white solid by preparative reverse-phase HPLC (15.3 mg, 51% yield), M+H=437.38的产率得到N-((R)-1-((S)-4-(4-Chlorophenyl)-4-fluoro-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)cyclopentanecarboxamide
  参考文献：
  名称：

  PIPERIDINYL DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

  摘要：

  本申请描述了MIP-1α或CCR-1的取代哌啶调节剂或其立体异构体或药学上可接受的盐。此外，还公开了使用所述调节剂治疗和预防炎症性疾病，如哮喘和过敏性疾病，以及自身免疫病理学，如类风湿性关节炎和移植排斥等的方法。

  公开号：

  US20090298833A1
• 作为产物：
  描述：

  Boc-D-缬氨酸 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)cyclopentanecarboxamide
  参考文献：
  名称：

  Discovery of the CCR1 Antagonist, BMS-817399, for the Treatment of Rheumatoid Arthritis

  摘要：

  High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavallable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.

  DOI：

  10.1021/jm5003167

文献信息

• PIPERIDINYL DERIVATIVE AS A MODULATOR OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Santella Joseph B.

  公开号：US20090326010A1

  公开（公告）日：2009-12-31

  The present application describes the compound of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and arthrosclerosis using the compound of the invention are disclosed.

  本申请描述了公式（I）的化合物：或其立体异构体或其药学上可接受的盐。此外，还披露了使用该发明的化合物治疗和预防炎症性疾病，如哮喘和过敏性疾病，以及自身免疫病理学，如类风湿性关节炎和动脉硬化的方法。
• PIPERIDINYL COMPOUND AS A MODULATOR OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Cherney Robert J.

  公开号：US20120149733A1

  公开（公告）日：2012-06-14

  The present application describes the compound of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and arthrosclerosis using the compound of the invention are disclosed.

  本申请描述了式(I)的化合物：或其立体异构体或其药学上可接受的盐。此外，本发明还揭示了使用该化合物治疗和预防炎症性疾病，如哮喘和过敏症，以及自身免疫病理如类风湿性关节炎和动脉硬化的方法。
• Piperidinyl derivatives as modulators of chemokine receptor activity
  申请人：Bristol-Myers Squibb Company

  公开号：US07985861B2

  公开（公告）日：2011-07-26

  The present application describes substituted piperidinyl modulators of MIP-1α or CCR-1 or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using said modulators are disclosed.

  本申请描述了替代的哌啶基MIP-1α或CCR-1调节剂或其立体异构体或药学上可接受的盐。此外，还揭示了使用所述调节剂治疗和预防哮喘和过敏性疾病以及自身免疫病理学，如类风湿性关节炎和移植排斥等炎症性疾病的方法。
• The discovery of BMS-457, a potent and selective CCR1 antagonist
  作者：Daniel S. Gardner、Joseph B. Santella、John V. Duncia、Percy H. Carter、T.G.Murali Dhar、Hong Wu、Weiwei Guo、Cullen Cavallaro、Katy Van Kirk、Melissa Yarde、Stephanie W. Briceno、R. Robert Grafstrom、Richard Liu、Sima R. Patel、Andrew J. Tebben、Dan Camac、Javed Khan、Andrew Watson、Guchen Yang、Anne Rose、William R. Foster、Mary Ellen Cvijic、Paul Davies、John Hynes

  DOI：10.1016/j.bmcl.2013.04.079

  日期：2013.7

  A series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis. (c) 2013 Elsevier Ltd. All rights reserved.
• US7601844B2
  申请人：——

  公开号：US7601844B2

  公开（公告）日：2009-10-13