5-cyano-N-[2-(4-isopropylphenyl)ethyl]-2-methoxy-N-methylbenzenesulfonamide | 524743-47-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 5-cyano-N-[2-(4-isopropylphenyl)ethyl]-2-methoxy-N-methylbenzenesulfonamide
• 英文别名: 5-cyano-2-methoxy-N-methyl-N-[2-(4-propan-2-ylphenyl)ethyl]benzenesulfonamide
• CAS: 524743-47-3
• 化学式: C₂₀H₂₄N₂O₃S
• 分子量: 372.488
• InChiKey: VVDSQFYJSPREST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-cyano-N-[2-(4-isopropylphenyl)ethyl]-2-methoxy-N-methylbenzenesulfonamide 在 lithium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-cyano-2-hydroxy-N-[2-(4-isopropylphenyl)ethyl]-N-methylbenzenesulfonamide
  参考文献：
  名称：

  Orally active factor Xa inhibitors: Investigation of a novel series of 3-amidinophenylsulfonamide derivatives using an amidoxime prodrug strategy

  摘要：

  A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy. We focused on systemic clearance of parent compounds in rats, and performed in vivo pharmacokinetic screening. Incorporation of a carboxymethoxy group markedly improved systemic clearance (compound 43), and the related amidoxime 44 showed sufficient prodrug conversion. Compound 45, the double prodrug of 43, exhibited practicable bioavailability after oral administration in rats. Among the various compounds under investigation, KFA-1982 was selected for clinical development. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.009
• 作为产物：
  描述：

  5-cyano-N-[2-(4-isopropylphenyl)ethyl]-2-methoxybenzene-sulfonamide 、 碘甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-cyano-N-[2-(4-isopropylphenyl)ethyl]-2-methoxy-N-methylbenzenesulfonamide
  参考文献：
  名称：

  Orally active factor Xa inhibitors: Investigation of a novel series of 3-amidinophenylsulfonamide derivatives using an amidoxime prodrug strategy

  摘要：

  A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy. We focused on systemic clearance of parent compounds in rats, and performed in vivo pharmacokinetic screening. Incorporation of a carboxymethoxy group markedly improved systemic clearance (compound 43), and the related amidoxime 44 showed sufficient prodrug conversion. Compound 45, the double prodrug of 43, exhibited practicable bioavailability after oral administration in rats. Among the various compounds under investigation, KFA-1982 was selected for clinical development. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.009

文献信息

• 5-amidino-2-hydroxybenzenesulfonamide derivatives medicinal compoistions containing the same medicinal use thereof and intermediates in the production thereof
  申请人：Uchida Masahiko

  公开号：US20050014787A1

  公开（公告）日：2005-01-20

  The present invention relates to a 5-amidino-2-hydroxybenzenesulfonamide derivative represented by the general formula: wherein R 1 is an optionally substituted lower alkyl group, an optionally substituted lower alkoxy group, an optionally substituted lower alkenyl group, a cycloalkyl group or a lower acyl group etc.; Q is a hydrogen atom or an optionally substituted lower alkyl group; and Z is a hydrogen atom or a hydroxy group etc., or a pharmaceutically acceptable salt thereof, which exert a potent and selective activated blood coagulation factor X inhibitory activity and is useful as an agent for the prevention or treatment of a disease occurred associating an activated blood coagulation factor X, a pharmaceutical composition comprising the same and an intermediate thereof. These compounds are useful as preventives or remedies for various diseases such as brain infarction, cerebral thrombosis, cerebral embolism, TIA, cerebral vascular jerk, Alzheimer's diseases, myocardial infarction, heart attack, heart failure, thrombosis, pulmonary infarction and pulmonary embolism.

  本发明涉及一种5-酰胺基-2-羟基苯磺酰胺衍生物，其通式表示为：其中，R1是可选取的取代的低烷基，可选取的取代的低烷氧基，可选取的取代的低烯基，环烷基或低酰基等；Q是氢原子或可选取的取代的低烷基；Z是氢原子或羟基等，或其药学上可接受的盐。该衍生物具有强效和选择性的激活血凝因子X抑制活性，可用作预防或治疗与激活血凝因子X相关的疾病的药物，以及包含该衍生物和其中间体的制药组合物。这些化合物可用作各种疾病的预防或治疗，例如脑梗死、脑血栓形成、脑栓塞、短暂性脑缺血发作、脑血管抽搐、阿尔茨海默病、心肌梗死、心脏病发作、心力衰竭、血栓形成、肺梗死和肺栓塞。
• Orally active factor Xa inhibitors: Investigation of a novel series of 3-amidinophenylsulfonamide derivatives using an amidoxime prodrug strategy
  作者：Masahiko Uchida、Kosuke Okazaki、Harunobu Mukaiyama、Hidetoshi Isawa、Hiroaki Kobayashi、Hiroaki Shiohara、Hideyuki Muranaka、Yuichiro Kai、Norihiko Kikuchi、Hideki Takeuchi、Kenji Yokoyama、Eiichi Tsuji、Tomonaga Ozawa、Yuji Hoyano、Takashi Koizumi、Keiko Misawa、Kiyoto Hara、Shigeru Nakano、Yasuoki Murakami、Hiroaki Okuno

  DOI：10.1016/j.bmcl.2008.07.009

  日期：2008.8

  A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy. We focused on systemic clearance of parent compounds in rats, and performed in vivo pharmacokinetic screening. Incorporation of a carboxymethoxy group markedly improved systemic clearance (compound 43), and the related amidoxime 44 showed sufficient prodrug conversion. Compound 45, the double prodrug of 43, exhibited practicable bioavailability after oral administration in rats. Among the various compounds under investigation, KFA-1982 was selected for clinical development. (C) 2008 Elsevier Ltd. All rights reserved.