2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride | 1140898-87-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: 2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride
• 英文别名: BMS-823778；1,2,4-Triazolo(4,3-a)pyridine-8-methanol, 3-(1-(4-chlorophenyl)cyclopropyl)-alpha,alpha-dimethyl-, hydrochloride (1:1)；2-[3-[1-(4-chlorophenyl)cyclopropyl]-[1,2,4]triazolo[4,3-a]pyridin-8-yl]propan-2-ol;hydrochloride
• CAS: 1140898-87-8
• 化学式: C₁₈H₁₈ClN₃O*ClH
• 分子量: 364.274
• InChiKey: MQBBSMNIRWXALO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.11
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride 在 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 2.33h， 生成 3-(1-(4-chlorophenyl)cyclopropyl)-8-(prop-1-en-2-yl)[1,2,4]triazolo[4,3-a]pyridine
  参考文献：
  名称：

  [EN] ISOTOPICALLY LABELED TRIAZOLOPYRIDINE 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE I INHIBITORS
  [FR] INHIBITEURS DE TRIAZOLOPYRIDINE 11-BÊTA HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1 À MARQUAGE ISOTOPIQUE

  摘要：

  提供了新的化合物，它们是11-beta-羟基类固醇脱氢酶I型抑制剂。11-beta-羟基类固醇脱氢酶I型抑制剂在治疗、预防或减缓需要11-beta-羟基类固醇脱氢酶I型抑制剂治疗的疾病方面非常有用。这些新的化合物的化学式为I：或其立体异构体或药学上可接受的盐，其中R*是同位素标记的羟丙基基团。

  公开号：

  WO2015061272A1
• 作为产物：
  描述：

  1-(4-chlorophenyl)-N'-(3-(2-hydroxypropan-2-yl)pyridin-2-yl)cyclopropanecarbohydrazide 在 溶剂黄146 、 盐酸 作用下， 以 甲苯 、 水 、 异丙醇 为溶剂， 反应 51.17h， 生成 2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride
  参考文献：
  名称：

  TRIAZOLOPYRIDINE 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE I INHIBITORS

  摘要：

  提供了一种新的化合物，它们是11-β-羟基类固醇脱氢酶I型抑制剂。11-β-羟基类固醇脱氢酶I型抑制剂在治疗、预防或减缓需要11-β-羟基类固醇脱氢酶I型抑制剂治疗的疾病的进展方面是有用的。这些具有式I的新化合物： 或其立体异构体或药用可接受的盐，其中G、Q、X、Y、R3、R3a和R3b在此处被定义。

  公开号：

  US20090093516A1

文献信息

• ISOTOPICALLY LABELED TRIAZOLOPYRIDINE 11-BETA HYDROXYSTEROID DEHYDROGENASE TYPE I INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160257680A1

  公开（公告）日：2016-09-08

  Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds of formula I: or stereoisomers or pharmaceutically acceptable salts thereof, wherein R* is an isotopically labeled hydroxypropyl moiety.

  提供了一种新型化合物，它们是11-β-羟基类固醇脱氢酶I型抑制剂。11-β-羟基类固醇脱氢酶I型抑制剂在治疗、预防或减缓需要11-β-羟基类固醇脱氢酶I型抑制剂治疗的疾病方面具有用途。这些新型化合物的化学式为I：或其立体异构体或药学上可接受的盐，其中R*是同位素标记的羟丙基基团。
• An Unexpected Degradation Pathway of a 1,2,4-Triazolo[4,3-a]pyridine Derivative: The Formation of 2 Cationic Pseudodimers of an 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Drug Candidate in a Stressed Capsule Formulation
  作者：Yande Huang、Qinggang Wang、Yongmei Wu

  DOI：10.1016/j.xphs.2018.02.009

  日期：2018.6

  Degradation of an active pharmaceutical ingredient (API), a 2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4] triazolo[4,3-alpyridin-8-yl)propan-2-ol hydrochloride salt, was observed in a capsule formulation stressed at 50 degrees C or 40 degrees C/75% relative humidity conditions for 1 month. Two unknown degradants were identified as cationic pseudodimers of the API via accurate mass liquid chromatography-mass spectrometry and 1- and 2-dimensional NMR analyses. A plausible degradation pathway of the API was postulated which led to the identification of 2 key N-oxide degradants in the stressed capsule formulation at trace levels. It was hypothesized that the N-oxide degradants could be protonated and undergo further transformation so as to react with another API free base to form pseudodimeric N-oxide intermediates, followed by protonation/dehydration to yield the cationic pseudodimers of the API. The proposed degradation pathway was further supported by formulation screening studies: (1) the removal of magnesium stearate (base/lubricant) from the formulation to reduce the formation of API free base, which is susceptible to oxidation to form N-oxides; (2) the replacement of API hydrochloride salt by its free base form to eliminate the proton source for protonation of the N-oxides so as to prevent their further transformation; and (3) the addition of anti-oxidants to minimize the oxidation of API free base to N-oxides. (C) 2018 American Pharmacists Association (R) . Published by Elsevier Inc. All rights reserved.
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  公开号：US8119658B2

  公开（公告）日：2012-02-21
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