N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide | 946585-25-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide
• 英文别名: N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-sulfamoylbenzamide
• CAS: 946585-25-7
• 化学式: C₂₅H₃₂ClN₃O₅S
• 分子量: 522.065
• InChiKey: YQAYHKVZTHFONF-BWKNWUBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  138
• 氢给体数：
  3
• 氢受体数：
  6

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)-3-sulfamoylbenzamide 在 超重氢 、 Crabtree's catalyst 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以41%的产率得到
  参考文献：
  名称：

  氚标记的 N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-的合成和表征2-基)-3-氨磺酰基苯甲酰胺

  摘要：

  N-((R)-1-((S)-4-(4-氯苯基)-4-羟基-3,3-二甲基哌啶-1-基)-3-甲基-1-氧代丁烷-2-基)- 3-氨磺酰苯甲酰胺是一种有效的 CC 趋化因子受体 1 (CCR1) 拮抗剂。该化合物具有苯甲酰胺官能团，成功地与有机铱催化剂（Crabtree 催化剂）进行氚/氢 (T/H) 交换。用液相色谱-质谱、飞行时间质谱和 (3) H-NMR 研究了产物中的标记模式。总体而言，鉴定了多个标记物种。除了预期在苯甲酰胺部分掺入氚之外，在分子的缬氨酸部分观察到氚标记，包括在其手性碳上的取代。使用正宗的标准，

  DOI：

  10.1002/jlcr.3320
• 作为产物：
  描述：

  4-(4-chloro-phenyl)-3,3-dimethyl-piperidin-4-ol 在 盐酸 、 L-酒石酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 生成 N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide
  参考文献：
  名称：

  The discovery of BMS-457, a potent and selective CCR1 antagonist

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2013.04.079

文献信息

• PIPERIDINYL DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Carter Percy H.

  公开号：US20070208056A1

  公开（公告）日：2007-09-06

  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，还公开了使用上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方法。
• 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。
• US7601844B2
  申请人：——

  公开号：US7601844B2

  公开（公告）日：2009-10-13