((2S,4S)-4-(trifluoromethyl)pyrrolidin-2-yl)methanol hydrochloride | 1283146-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: ((2S,4S)-4-(trifluoromethyl)pyrrolidin-2-yl)methanol hydrochloride
• 英文别名: [(2S,4S)-4-(trifluoromethyl)pyrrolidin-2-yl]methanol hydrochloride；[(2S,4S)-4-(trifluoromethyl)pyrrolidin-2-yl]methanol;hydrochloride
• CAS: 1283146-07-5
• 化学式: C₆H₁₀F₃NO*ClH
• 分子量: 205.608
• InChiKey: BFOBDQVXVWGSBY-FHAQVOQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.94
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ((2S,4S)-4-(trifluoromethyl)pyrrolidin-2-yl)methanol hydrochloride 在 copper(l) iodide 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 二甲基亚砜 、 异丙醇 为溶剂， 反应 1.0h， 生成 2-((2S,4S)-1-(4-(2-methylbenzyl)phenyl)-4-(trifluoromethyl)pyrrolidin-2-yl)acetonitrile
  参考文献：
  名称：

  Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode

  摘要：

  A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding K-i and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both G(q)-coupled intracellular Ca2+ flux and G(s)-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.

  DOI：

  10.1021/acs.jmedchem.6b01559
• 作为产物：
  描述：

  在 盐酸 、 sodium tetrahydroborate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 ((2S,4S)-4-(trifluoromethyl)pyrrolidin-2-yl)methanol hydrochloride
  参考文献：
  名称：

  Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode

  摘要：

  A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding K-i and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both G(q)-coupled intracellular Ca2+ flux and G(s)-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.

  DOI：

  10.1021/acs.jmedchem.6b01559

文献信息

• PYRIDAZINONES AS PARP7 INHIBITORS
  申请人：Ribon Therapeutics Inc.

  公开号：US20190330194A1

  公开（公告）日：2019-10-31

  The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.

  本发明涉及吡啶并嗪酮和相关化合物，它们是PARP7的抑制剂，并且在癌症治疗中很有用。
• Pyridazinones as PARP7 inhibitors
  申请人：Ribon Therapeutics Inc.

  公开号：US10550105B2

  公开（公告）日：2020-02-04

  The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.

  本发明涉及哒嗪酮类及相关化合物，它们是 PARP7 的抑制剂，可用于治疗癌症。