二氟阿托伐他汀 | 693794-20-6

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 二氟阿托伐他汀
• 中文别名: 阿托伐他汀钙杂质
• 英文名称: (3R,5R)-7-[2,3-di-(4-fluorophenyl)-5-isopropyl-4-(phenylamino)-carbonyl]-1H-pyrrol-3,5-dihydroxy-1-heptanoic acid
• 英文别名: Fluoroatorvastatin；(3R,5R)-7-[2,3-bis(4-fluorophenyl)-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid
• CAS: 693794-20-6
• 化学式: C₃₃H₃₄F₂N₂O₅
• 分子量: 576.64
• InChiKey: UNKLVVGSJZVOBR-KAYWLYCHSA-N

物化性质

• 沸点：
  720.7±60.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  112
• 氢给体数：
  4
• 氢受体数：
  7

制备方法与用途

生物活性

Difluoro atorvastatin（氟代阿托伐他汀）是阿托伐他汀的一种杂质。阿托伐他汀是一种口服活性的HMG-CoA还原酶抑制剂，能够有效降低血脂水平。实验表明，阿托伐他汀以IC50分别为0.39 μM和2.39 μM来抑制人SV-SMC的增殖和侵袭。

文献信息

• Substituted pyrrole derivatives
  申请人：——

  公开号：US20040102511A1

  公开（公告）日：2004-05-27

  The present invention relates to substituted pyrrole derivatives, which can be used as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Compounds disclosed herein can function as cholesterol lowering agents and can be used for the treatment of cholesterol-related diseases and related symptoms. Processes for the preparation of disclosed compounds are provided, as well as, pharmaceutical compositions containing the disclosed compounds, and methods of treating cholesterol-related diseases and related symptoms.

  本发明涉及取代吡咯衍生物，可用作3-羟基-3-甲基戊二酸辅酶A（HMG-CoA）还原酶抑制剂。本文披露的化合物可作为降胆固醇剂，并可用于治疗胆固醇相关疾病和相关症状。提供了制备披露化合物的过程，以及包含披露化合物的药物组合物，以及治疗胆固醇相关疾病和相关症状的方法。
• [EN] AN IMPROVED AND COMMERCIALLY VIABLE PROCESS FOR PREPARATION OF PYRROLE DERIVATIVES WITH IMPROVED IMPURITY PROFILE & MINIMISATION OF UNIT OPERATIONS.<br/>[FR] PROCÉDÉ AMÉLIORÉ ET VIABLE SUR LE PLAN COMMERCIAL POUR LA PRÉPARATION DE DÉRIVÉS DE PYRROLE AYANT UN PROFIL D'IMPURETÉS AMÉLIORÉ EN VUE D'UNE RÉDUCTION AU MINIMUM D'OPÉRATIONS UNITAIRES
  申请人：ARCH PHARMALABS LTD

  公开号：WO2020016903A1

  公开（公告）日：2020-01-23

  The present invention relates to improved process for the preparation of a pyrrole derivative as a racemic mixture, an enantiomer, a diastereoisomer, a mixture thereof, a tautomer thereof or a pharmaceutically acceptable salt and hydrates thereof and also intermediates involved therein. Particularly invention is directed to improved processes for the preparation of pyrrole derivatives such as (4R,cis)-6-[2-[3-phenyl-4-(phenyl-carbamoyl)-2-(4-fluorophenyl)-5-(1-methyl-ethyl)-pyrrole-1-yl]-2,2-dimethyl-[1,3]dioxane-4-yl-acetic acid-tertiary butyl ester of formula IV followed by its conversion into [R-(R*, R*]-2-(4-fluorophenyl)- β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1- heptanoic acid particularly calcium salt and its hydrate represented by Formulae I/IA respectively wherein formation of the impurities is either eliminated or minimized in the corresponding intermediaries.

  本发明涉及改进的过程，用于制备吡咯衍生物的混合物，对映体，非对映异构体，其混合物，其互变异构体或其药学上可接受的盐和水合物，以及涉及其中间体。特别是本发明涉及改进的过程，用于制备吡咯衍生物，如公式IV的（4R，顺式）-6- [2- [3-苯基-4-（苯基-氨基甲酰）-2-（4-氟苯基）-5-（1-甲基乙基）-吡咯-1-基] -2,2-二甲基-[1,3]二氧杂环-4-基乙酸叔丁酯，然后将其转化为[R-（R *，R *] -2-（4-氟苯基）-β，δ-二羟基-5-（1-甲基乙基）-3-苯基-4-[(苯氨基）甲酰]-1H-吡咯-1-庚酸，特别是钙盐及其水合物，分别由公式I / IA表示，其中在相应的中间体中消除或最小化杂质的形成。
• Novel Crystalline Form of Atorvastatin Hemi-calcium Salt, Hydrate Thereof, And Method of Producing The Same
  申请人：KYONGBO PHARM

  公开号：US20140081033A1

  公开（公告）日：2014-03-20

  The present invention provides a novel crystalline form of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-mthylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-heptanoic acid hemi-calcium salt (atorvastatin hemi-calcium salt) of the following formula 1, which is known to be useful as a drug, a hydrate thereof and a preparation method thereof: