S-[4-(N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-chlorophenyl}carbamoyl)phenyl]-S-methyl-N-benzyloxycarbonyl sulfoximide | 1147096-54-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: S-[4-(N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-chlorophenyl}carbamoyl)phenyl]-S-methyl-N-benzyloxycarbonyl sulfoximide
• 英文别名: S-[4-(N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-chloro phenyl}carbamoyl)phenyl]-S-methyl-N-benzyloxycarbonyl Sulfoximide；benzyl N-[[4-[[4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]phenyl]carbamoyl]phenyl]-methyl-oxo-λ6-sulfanylidene]carbamate
• CAS: 1147096-54-5
• 化学式: C₂₈H₂₂Cl₂N₄O₅S
• 分子量: 597.478
• InChiKey: XKSWVYDNKQWZDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  S-[4-(N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-chlorophenyl}carbamoyl)phenyl]-S-methyl-N-benzyloxycarbonyl sulfoximide 在 硫酸 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(diethylglycyl)-S-methylsulfonimidoyl)benzamido)benzamide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of potent, selective and orally active anthranilamide-based factor Xa inhibitors: Application of weakly basic sulfoximine group as novel S4 binding element

  摘要：

  A novel series of potent and efficacious factor Xa inhibitors which possesses sulfoximine moiety as novel S4 binding element in anthranilamide chemotype has been identified. Lead optimization at this novel P4 group led to many potent factor Xa inhibitors with excellent anticoagulant activity in human plasma. Selected compounds were dosed orally in rats and checked for their ex vivo prothrombin time prolonging activity, which resulted in identification of compound 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(2(diethylamino)acetyl)-S-methylsulfonimidoyl)benzamido)benzamide (18f). The detailed pharmacokinetic evaluation and subsequent metabolism study of 181 suggested the presence of an active metabolite. The compound 18f and its active metabolite 18b demonstrated excellent in vivo efficacy in both arterial and venous thrombosis model in rats and were found to be highly selective against related serine proteases. Based on this promising profile, compound 18f was selected for further evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.005
• 作为产物：
  描述：

  4-(甲基硫代)苯甲酸甲酯 在 N,N-二甲基甲酰胺 吡啶 、 sodium azide 、 草酰氯 、 硫酸 、 水 、 vanadia 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 36.0h， 生成 S-[4-(N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-chlorophenyl}carbamoyl)phenyl]-S-methyl-N-benzyloxycarbonyl sulfoximide
  参考文献：
  名称：

  SULFOXIMINE DERIVATIVES AS FACTOR XA INHIBITORS

  摘要：

  本发明涉及一种新型的通式（I）的取代砜肟衍生物，其互变异构体，立体异构体，药学上可接受的盐，含有它们的药物组合物，它们的制备方法，这些化合物在医学上的应用以及其制备中涉及的中间体。

  公开号：

  US20110065717A1

文献信息

• SULFOXIMINE DERIVATIVES AS FACTOR XA INHIBITORS
  申请人：Pandya Vrajesh B.

  公开号：US20110065717A1

  公开（公告）日：2011-03-17

  The present invention relates to novel substituted sulfoximine derivatives of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

  本发明涉及一种新型的通式（I）的取代砜肟衍生物，其互变异构体，立体异构体，药学上可接受的盐，含有它们的药物组合物，它们的制备方法，这些化合物在医学上的应用以及其制备中涉及的中间体。
• Sulfoxamine derivatives as factor Xa inhibitors
  申请人：Cadila Healthcare Limited

  公开号：US08227492B2

  公开（公告）日：2012-07-24

  The present invention relates to novel substituted sulfoximine derivatives of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

  本发明涉及一种新的一般式（I）的取代亚磺酰胺衍生物，它们的互变异构体，立体异构体，药学上可接受的盐，含有它们的制药组合物，它们的制备方法，这些化合物在医学中的应用以及其制备中涉及的中间体。
• Synthesis and structure–activity relationship of potent, selective and orally active anthranilamide-based factor Xa inhibitors: Application of weakly basic sulfoximine group as novel S4 binding element
  作者：Vrajesh Pandya、Mukul Jain、Ganes Chakrabarti、Hitesh Soni、Bhavesh Parmar、Balaji Chaugule、Jigar Patel、Tushar Jarag、Jignesh Joshi、Nirav Joshi、Akshyaya Rath、Vishal Unadkat、Bhavesh Sharma、Haresh Ajani、Jeevan Kumar、Kalapatapu V.V.M. Sairam、Harilal Patel、Pankaj Patel

  DOI：10.1016/j.ejmech.2012.10.005

  日期：2012.12

  A novel series of potent and efficacious factor Xa inhibitors which possesses sulfoximine moiety as novel S4 binding element in anthranilamide chemotype has been identified. Lead optimization at this novel P4 group led to many potent factor Xa inhibitors with excellent anticoagulant activity in human plasma. Selected compounds were dosed orally in rats and checked for their ex vivo prothrombin time prolonging activity, which resulted in identification of compound 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(2(diethylamino)acetyl)-S-methylsulfonimidoyl)benzamido)benzamide (18f). The detailed pharmacokinetic evaluation and subsequent metabolism study of 181 suggested the presence of an active metabolite. The compound 18f and its active metabolite 18b demonstrated excellent in vivo efficacy in both arterial and venous thrombosis model in rats and were found to be highly selective against related serine proteases. Based on this promising profile, compound 18f was selected for further evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.