AZD 7687; [反式-4-[4-(6-氨基甲酰基-3,5-二甲基吡嗪-2-基)苯基]环己基]乙酸 | 1166827-44-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: AZD 7687; [反式-4-[4-(6-氨基甲酰基-3,5-二甲基吡嗪-2-基)苯基]环己基]乙酸
• 中文别名: [反式-4-[4-(6-氨基甲酰基-3,5-二甲基吡嗪-2-基)苯基]环己基]乙酸；AZD7687;[反式-4-[4-(6-氨基甲酰基-3,5-二甲基吡嗪-2-基)苯基]环己基]乙酸
• 英文名称: {trans-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl}acetic acid
• 英文别名: {4-[4-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl}acetic acid；2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl]acetic acid
• CAS: 1166827-44-6
• 化学式: C₂₁H₂₅N₃O₃
• 分子量: 367.448
• InChiKey: YXFNPRHZMOGREC-UHFFFAOYSA-N

物化性质

• 沸点：
  527.5±50.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	1-O-({trans-4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenyl]cyclohexyl}acetyl)-β-D-glucopyranuronic acid	1414867-53-0	C27H33N3O9	543.574

反应信息

• 作为反应物：
  描述：

  AZD 7687; [反式-4-[4-(6-氨基甲酰基-3,5-二甲基吡嗪-2-基)苯基]环己基]乙酸 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 50.0h， 以72%的产率得到6-{4-[trans-4-(carboxymethyl)cyclohexyl]phenyl}-3,5-dimethylpyrazine-2-carboxylic acid
  参考文献：
  名称：

  Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)

  摘要：

  A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

  DOI：

  10.1021/jm301296t
• 作为产物：
  描述：

  4-(4-羟基苯基)环己酮 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium dihydrogenphosphate 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 sodium hydride 、 氯化铵 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 140.0 ℃ 、500.01 kPa 条件下， 反应 23.0h， 生成 AZD 7687; [反式-4-[4-(6-氨基甲酰基-3,5-二甲基吡嗪-2-基)苯基]环己基]乙酸
  参考文献：
  名称：

  Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)

  摘要：

  A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

  DOI：

  10.1021/jm301296t

文献信息

• [EN] CARBAMOYL COMPOUNDS AS DGAT1 INHIBITORS 190<br/>[FR] COMPOSÉS CARBAMOYLES COMME INHIBITEURS DE DGAT1 190
  申请人：ASTRAZENECA AB

  公开号：WO2009081195A1

  公开（公告）日：2009-07-02

  DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro- drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is =O; Ring B is optionally substituted 1,4-phenylene; Y1 is a direct bond or -O-; Y2 is -(CH 2) r- wherein r is 2 or 3; n is 0 or n is 1 when Y1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or -O-; p is 0, 1 or 2 and when p is 1 or 2 RA1 and RA2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

  DGAT-1抑制剂化合物公式(I)，药用可接受的盐和前药，以及药物组合物、制造它们的过程以及它们在治疗例如肥胖症中的用途，其中，例如，环A是可选取代的2,6-吡嗪二基；X是=O；环B是可选取代的1,4-苯基；Y1是直接键或-O-；Y2是-(CH2)r-，其中r是2或3；n是0或当Y1是环B和环C之间的直接键并且当环B是1,4-苯基和环C是(4-6C)环烷时，n是1；环C是可选取代的(4-6C)环烷、(7-10C)双环烷、(8-12C)三环烷、苯基或吡啶二基；L是直接键或-O-；p是0、1或2，并且当p是1或2时，RA1和RA2各自独立地为氢或(1-4C)烷基；Z是羧酸或其模拟物或生物等排体。
• Carbamoyl Compounds as DGAT1 Inhibitors 190
  申请人：Bauer Udo Andreas

  公开号：US20090298853A1

  公开（公告）日：2009-12-03

  DGAT-1 inhibitor compounds of formula (I), pharmaceutically-acceptable salts and pro-drugs thereof are described, together with pharmaceutical compositions, processes for making them and their use in treating, for example, obesity wherein, for example, Ring A is optionally substituted 2,6-pyrazindiyl; X is ═O; Ring B is optionally substituted 1,4-phenylene; Y 1 is a direct bond or —O—; Y 2 is —(CH 2 ) r — wherein r is 2 or 3; n is 0 or n is 1 when Y 1 is a direct bond between Ring B and Ring C and when Ring B is 1,4-phenylene and Ring C is (4-6C)cycloalkane; Ring C is optionally substituted (4-6C)cycloalkane, (7-10C)bicycloalkane, (8-12C)tricycloalkane, phenylene or pryidindiyl; L is a direct bond or —O—; p is 0, 1 or 2 and when p is 1 or 2 R A1 and R A2 are each independently hydrogen or (1-4C)alkyl; Z is carboxy or a mimic or bioisostere thereof.

  本文介绍了公式（I）的DGAT-1抑制剂化合物，其药学上可接受的盐和前药，以及制备它们的制药组合物、制备过程和用于治疗肥胖等疾病的用途。其中，例如，环A是可选取代的2,6-吡唑二基；X是 ═O；环B是可选取代的1,4-苯基；Y1是直接键或—O—；Y2是—（CH2）r—，其中r为2或3；当Y1是环B和环C之间的直接键时，n为0或1，当环B是1,4-苯基，环C是（4-6C）环烷基时，n为1；环C是可选取代的（4-6C）环烷基，（7-10C）双环烷基，（8-12C）三环烷基，苯基或吡啶二基；L是直接键或—O—；p为0、1或2，当p为1或2时，RA1和RA2各自独立地为氢或（1-4C）烷基；Z为羧基或其类似物或生物同位素。
• DGAT1 inhibition for treatment of demyelinating inflammatory disease
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10226470B2

  公开（公告）日：2019-03-12

  Methods are provided for treating autoimmune disease in a subject by inhibiting the activity of DGAT1.

  提供了通过抑制 DGAT1 的活性来治疗受试者自身免疫性疾病的方法。
• CARBAMOYL COMPOUNDS AS DGAT1 INHIBITORS 190
  申请人：AstraZeneca AB

  公开号：EP2234978B1

  公开（公告）日：2015-02-25
• METHOD OF TREATING SKIN CONDITIONS
  申请人：Astrazeneca AB

  公开号：EP3177293A1

  公开（公告）日：2017-06-14