(3R,3aR)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate | 1023650-29-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (3R,3aR)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate
• 英文别名: (3R,3aR)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid；(3R,3aR)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydrobenzo[g]indazole-7-carboxylic acid
• CAS: 1023650-29-4
• 化学式: C₂₅H₁₇ClFN₃O₂
• 分子量: 445.88
• InChiKey: ABRSQONXUKMPNK-URXFXBBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲基磺酰胺 、 (3R,3aR)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以39%的产率得到(+/-)-(3RS,3aRS)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-N-(methylsulfonyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxamide
  参考文献：
  名称：

  WO2008/53300

  摘要：

  公开号：
• 作为产物：
  描述：

  (+/-)-(3RS,3aRS)-ethyl 2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以96%的产率得到(3R,3aR)-2-(3-chloro-4-cyanophenyl)-3-(4-fluorophenyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate
  参考文献：
  名称：

  Discovery of (3S,3aR)-2-(3-Chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic Acid (PF-3882845), an Orally Efficacious Mineralocorticoid Receptor (MR) Antagonist for Hypertension and Nephropathy

  摘要：

  We have discovered a novel class of nonsteroidal pyrazoline antagonists of the mineralocorticoid receptor (M R) that show excellent potency and selectivity against other nuclear receptors. Early analogues were poorly soluble and had a propensity to inhibit the hERG channel. Remarkably, both of these challenges were overcome by incorporation of a single carboxylate moiety. Structural modification of carboxylate-containing lead R-4g with a wide range of substituents at each position of the pyrazoline ring resulted in R-12o, which shows excellent activity against MR and reasonable pharmacokinetic profile. Introduction of conformational restriction led to a novel series characterized by exquisite potency and favorable steroid receptor selectivity and pharmacokinetic profile. Oral dosing of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt-induced hypertension and nephropathy showed blood pressure attenuation significantly greater than that with eplerenone, reduction in urinary albumin, and renal protection. As a result of these findings, 3S,3aR-27d was advanced to clinical studies.

  DOI：

  10.1021/jm100505n

文献信息

• Pyrazoline Compounds
  申请人：Meyers Marvin J.

  公开号：US20080167294A1

  公开（公告）日：2008-07-10

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R 1 , R 2 , R 3A , R 3B , R 4 , R 5 , R 6 , R 7 , R 8 , and X are as defined in the detailed description of the invention. Corresponding pharmaceutical compositions, methods of treatment, and intermediates are also disclosed.

  公开了化合物和药物可接受的盐，其中化合物具有公式I的结构:其中R1，R2，R3A，R3B，R4，R5，R6，R7，R8和X如发明的详细说明中所定义的那样。还公开了相应的药物组合物，治疗方法和中间体。
• PYRAZOLINE COMPOUNDS
  申请人：Meyers Marvin J.

  公开号：US20100280016A1

  公开（公告）日：2010-11-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R 1 , R 2 , R 3A , R 3B , R 4 , R 5 , R 6 , R 7 , R 8 , and X are as defined in the detailed description of the invention. Corresponding pharmaceutical compositions, methods of treatment, and intermediates are also disclosed.

  本发明披露了具有I式结构的化合物及其药学上可接受的盐，其中化合物的结构如下：其中R1、R2、R3A、R3B、R4、R5、R6、R7、R8和X的定义详见发明的详细说明。本发明还披露了相应的药物组合物、治疗方法和中间体。
• Pyrazoline compounds
  申请人：Pfizer Inc.

  公开号：US07781428B2

  公开（公告）日：2010-08-24

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: wherein R1, R2, R3A, R3B, R4, R5, R6, R7, R8, and X are as defined in the detailed description of the invention. Corresponding pharmaceutical compositions, methods of treatment, and intermediates are also disclosed.

  本发明揭示了化合物及其药学上可接受的盐，其中化合物具有公式I的结构：其中R1、R2、R3A、R3B、R4、R5、R6、R7、R8和X的定义详见本发明的详细说明。本发明还揭示了相应的药物组合物、治疗方法和中间体。
• PYRAZOLINE COMPOUNDS AS MINERALOCORTICOID RECEPTOR ANTAGONISTS
  申请人：Pfizer Products Inc.

  公开号：EP2089367B1

  公开（公告）日：2011-12-14
• US7781428B2
  申请人：——

  公开号：US7781428B2

  公开（公告）日：2010-08-24