(3R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester | 950599-45-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (3R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester
• 英文别名: methyl (E,3R)-7-[3-(4-fluorophenyl)-4-phenyl-5-(phenylcarbamoyl)-1-propan-2-ylpyrrol-2-yl]-3-hydroxy-5-oxohept-6-enoate
• CAS: 950599-45-8
• 化学式: C₃₄H₃₃FN₂O₅
• 分子量: 568.645
• InChiKey: HTFMULIGYOWJGG-RSGAMAQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester 在 palladium on activated charcoal sodium tetrahydroborate 、 二乙基甲氧基硼烷 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 5.0h， 生成 (3R,5R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3,5-dihydroxyheptanoic acid methyl ester
  参考文献：
  名称：

  Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors

  摘要：

  This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.096
• 作为产物：
  描述：

  4-(4-fluoro-phenyl)-5-formyl-1-isopropyl-3-phenyl-1H-pyrrole-2-carboxylic acid ethyl ester 在 sodium hydroxide 、 氯化亚砜 、 氢氟酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 64.0h， 生成 (3R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester
  参考文献：
  名称：

  Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors

  摘要：

  This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.096

文献信息

• [EN] N-ALKYL PYRROLES AS HMG-COA REDUCTASE INHIBITORS<br/>[FR] PYRROLES DE N-ALKYL COMME INHIBITEURS DE L'HMG-COA-REDUCTASE
  申请人：WARNER LAMBERT CO

  公开号：WO2005056004A1

  公开（公告）日：2005-06-23

  HMGCo-A reductase inhibitor compounds useful as hypocholesterolemic and hypolipidemic compounds are provided. Also provided are pharmaceutical compositions of the compounds. Methods of making and methods of using the compounds are also provided. Formula (I).

  提供了作为降胆固醇和降脂化合物有用的HMGCo-A还原酶抑制剂化合物。还提供了这些化合物的药物组合物。还提供了制备这些化合物的方法和使用这些化合物的方法。公式（I）。
• N-alkyl pyrroles as HMG-CoA reductase inhibitors
  申请人：Bratton D. Larry

  公开号：US20050154042A1

  公开（公告）日：2005-07-14

  HMGCo-A reductase inhibitor compounds useful as hypocholesterolemic and hypolipidemic compounds are provided. Also provided are pharmaceutical compositions of the compounds. Methods of making and methods of using the compounds are also provided.

  提供了作为降低胆固醇和降脂化合物有用的HMGCo-A还原酶抑制剂化合物。还提供了该化合物的药物组成物。还提供了制备该化合物的方法和使用该化合物的方法。
• 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene derivatives and their use as renin inhibitors in the treatment of hypertension,cardiovascular or renal diseases
  申请人：Bezencon Olivier

  公开号：US20050176700A1

  公开（公告）日：2005-08-11

  The invention relates to novel 3,9-diazabicyclo[3.3.1]nonene derivatives of formula (I) and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors or renin.

  本发明涉及式(I)的新型3,9-二氮杂双环[3.3.1]壬烯衍生物及其相关化合物，以及它们作为药物组分在制备药物组合物中的应用。本发明还涉及相关方面，包括制备这些化合物的过程、含有其中一个或多个这些化合物的药物组合物，尤其是它们作为肾素抑制剂的应用。
• N-ALKYL PYRROLES AS HMG-COA REDUCTASE INHIBITORS
  申请人：Warner-Lambert Company LLC

  公开号：EP1691803A1

  公开（公告）日：2006-08-23
• Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors
  作者：Jeffrey A. Pfefferkorn、Yuntao Song、Kuai-Lin Sun、Steven R. Miller、Bharat K. Trivedi、Chulho Choi、Roderick J. Sorenson、Larry D. Bratton、Paul C. Unangst、Scott D. Larsen、Toni-Jo Poel、Xue-Min Cheng、Chitase Lee、Noe Erasga、Bruce Auerbach、Valerie Askew、Lisa Dillon、Jeffrey C. Hanselman、Zhiwu Lin、Gina Lu、Andrew Robertson、Karl Olsen、Thomas Mertz、Catherine Sekerke、Alexander Pavlovsky、Melissa S. Harris、Graeme Bainbridge、Nicole Caspers、Huifen Chen、Matthias Eberstadt

  DOI：10.1016/j.bmcl.2007.05.096

  日期：2007.8

  This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models. (c) 2007 Elsevier Ltd. All rights reserved.