[3-(5-cyano-pyrazol-1-yl)-1-(4-methyl-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester | 1191030-35-9

• 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: [3-(5-cyano-pyrazol-1-yl)-1-(4-methyl-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[4-(5-cyanopyrazol-1-yl)-1-(4-methylpiperidin-1-yl)-1-oxobutan-2-yl]carbamate
• CAS: 1191030-35-9
• 化学式: C₁₉H₂₉N₅O₃
• 分子量: 375.471
• InChiKey: GOAVZKQJEHMZGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [3-(5-cyano-pyrazol-1-yl)-1-(4-methyl-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester 在 trialkylamine 作用下， 生成 4-amino-3,5-dichloro-N-{3-(5-cyano-1H-pyrazol-1-yl)-1-[(4-methylpiperidin-1-yl)carbonyl]propyl}benzenesulfonamide
  参考文献：
  名称：

  N-Arylsulfonyl-α-amino carboxamides are potent and selective inhibitors of the chemokine receptor CCR10 that show efficacy in the murine DNFB model of contact hypersensitivity

  摘要：

  Compound 1 ((4-amino-3,5-dichloropheny1)-1-(4-methylpiperidin-1-y1)-4-(2-nitroimidazol-1-y1)-1oxobutane-2-sulfonamido) was discovered to be a 690 nM antagonist of human CCR10 Ca2+ flux. Optimization delivered (2R)-4-(2-cyanopyrrol-1-y1)-S-(1H-indo1-4-y1)-1-(4-methylpiperidin-l-y1)-1oxobutane-2-sulfonamido (eut-22) that is 300 fold more potent a CCR10 antagonist than 1 and eliminates potential toxicity, mutagenicity, and drug-drug-interaction liabilities often associated with nitroaryls and anilines. eut-22 is highly selective over other GPCR's, including a number of other chemokine receptors. Finally, eut-22 is efficacious in the murine DNFB model of contact hypersensitivity. The efficacy of this compound provides further evidence for the role of CCR10 in dermatological inflammatory conditions. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.

  DOI：

  10.1016/j.bmcl.2016.09.047
• 作为产物：
  描述：

  zinc(II) cyanide 、 [3-(5-bromo-pyrazol-1-yl)-1-(4-methyl-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester 在 tris-(dibenzylideneacetone)dipalladium(0) 锌 作用下， 以 二甲胺 为溶剂， 反应 3.0h， 以74%的产率得到[3-(5-cyano-pyrazol-1-yl)-1-(4-methyl-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] 2-SULFONYLAMINO-4-HETEROARYL BUTYRAMIDE ANTAGONISTS OF CCR10
  [FR] ANTAGONISTES DE 2-SULFONYLAMINO-4-HÉTÉROARYL BUTYRAMIDE DE CCR10

  摘要：

  本发明涉及一种具有式（I）的化合物及其药学上可接受的盐，其中R1、R2、R4、Ar和Het如本文中所定义。该发明还涉及使用式（I）的化合物治疗通过CCR10活性介导或维持的疾病和紊乱的方法。

  公开号：

  WO2009126675A1

文献信息

• 2-SULFONYLAMINO-4-HETEROARYL BUTYRAMIDE ANTAGONISTS OF CCR10
  申请人：Abeywardane Asitha

  公开号：US20110275800A1

  公开（公告）日：2011-11-10

  This invention relates to a compound of formula (I) and the pharmaceutically acceptable salts thereof wherein R 1 , R 2 , R 4 . Ar and Het are as defined herein. The invention also relates to methods of using the compound of formula (I) to treat a diseases and disorders that are mediated or sustained through the activity of CCR 10 .

  本发明涉及公式(I)的化合物及其药学上可接受的盐，其中R1、R2、R4、Ar和Het的定义如本文所述。本发明还涉及使用公式(I)的化合物治疗通过CCR10活性介导或持续的疾病和障碍的方法。
• 2-sulfonylamino-4-heteroaryl butyramide antagonists of CCR10
  申请人：Abeywardane Asitha

  公开号：US08586748B2

  公开（公告）日：2013-11-19

  This invention relates to a compound of formula (I) and the pharmaceutically acceptable salts thereof wherein R1, R2, R4. Ar and Het are as defined herein. The invention also relates to methods of using the compound of formula (I) to treat a diseases and disorders that are mediated or sustained through the activity of CCR10.

  本发明涉及式(I)化合物及其药学上可接受的盐，其中R1、R2、R4、Ar和Het如本文所定义。本发明还涉及使用式(I)化合物的方法，用于治疗通过CCR10活性介导或维持的疾病和障碍。
• 2-SULFONYLAMINO-4-HETEROARYL BUTYRAMIDE ANTAGONISTS OF CCR10
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2276731A1

  公开（公告）日：2011-01-26
• US8586748B2
  申请人：——

  公开号：US8586748B2

  公开（公告）日：2013-11-19
• [EN] 2-SULFONYLAMINO-4-HETEROARYL BUTYRAMIDE ANTAGONISTS OF CCR10<br/>[FR] ANTAGONISTES DE 2-SULFONYLAMINO-4-HÉTÉROARYL BUTYRAMIDE DE CCR10
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2009126675A1

  公开（公告）日：2009-10-15

  This invention relates to a compound of formula (I) and the pharmaceutically acceptable salts thereof wherein R1, R2, R4. Ar and Het are as defined herein. The invention also relates to methods of using the compound of formula (I) to treat a diseases and disorders that are mediated or sustained through the activity of CCR10.

  本发明涉及一种具有式（I）的化合物及其药学上可接受的盐，其中R1、R2、R4、Ar和Het如本文中所定义。该发明还涉及使用式（I）的化合物治疗通过CCR10活性介导或维持的疾病和紊乱的方法。