8-chloro-11-(1-(methylsulfonyl)piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: 8-chloro-11-(1-(methylsulfonyl)piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
• 英文别名: 8-Chloro-11-(1-methanesulfonyl-piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine；13-Chloro-2-(1-methylsulfonylpiperidin-4-ylidene)-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene
• 化学式: C₂₀H₂₁ClN₂O₂S
• 分子量: 388.918
• InChiKey: YDDVSUDVRYZXAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  氯雷他定 在 盐酸 、 potassium carbonate 作用下， 以 水 、 甲苯 为溶剂， 生成 8-chloro-11-(1-(methylsulfonyl)piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
  参考文献：
  名称：

  Novel tricyclic aminoacetyl and sulfonamide inhibitors of Ras farnesyl protein transferase

  摘要：

  Novel tricyclic FPT inhibitors with submicromolar FPT activity are described. Greatly enhanced FPT activity is realized with phthaloyl derivatized amino compound 2k, which showed FPT inhibitory activity of IC50 = 0.66 mu M. Sulfonamides 5g and 50 were also found to be potent FPT inhibitor. SAR resulting from a variety of tricyclic amino acids and sulfonamide derivatives is discussed. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00558-6

文献信息

• Synthesis of Isomeric 3-Piperidinyl and 3-Pyrrolidinyl Benzo[5,6]cyclohepta[1,2-b]pyridines: Sulfonamido Derivatives as Inhibitors of Ras Prenylation
  作者：Joseph Kelly、Ronald Wolin、Michael Connolly、Adriano Afonso、Linda James、Paul Kirshmeier、W.Robert Bishop、Andrew T. McPhail

  DOI：10.1016/s0968-0896(98)00026-1

  日期：1998.6

  Blocking farnesylation of oncogenic Ras proteins is a mechanism based therapeutic approach that is of current interest for the development of antitumor agents to treat ras associated tumors. As part of a SAR study on the lead farnesyl protein transferase (FPT) inhibitor I, we report here the synthesis of novel geometric isomers II and III and the FPT inhibition activity of their N-acyl and N-sulfonamido

  阻断致癌性Ras蛋白的法尼基化是一种基于机制的治疗方法，目前对于开发治疗ras相关肿瘤的抗肿瘤药物具有重要意义。作为对法呢基铅蛋白转移酶（FPT）抑制剂I的SAR研究的一部分，我们在这里报告了新型几何异构体II和III的合成及其N-酰基和N-磺酰胺基衍生物15-65的FPT抑制活性。N-酰基衍生物的活性显着低于铅抑制剂I，从而表明I中N-酰基的空间位置对于化合物与FPT的结合至关重要。与I相反，N-磺酰胺基-II系列是非巯基非肽类化合物的新型先导，它们是FPT / GGPT双重抑制剂。根据最近有关N-和K-Ras异戊烯化的报道，
• [EN] TRICYCLIC COMPOUND AND PHARMACEUTICAL USE THEREOF<br/>[FR] COMPOSÉ TRICYCLIQUE ET SON UTILISATION PHARMACEUTIQUE<br/>[KO] 삼환식 화합물 및 이의 약학적 용도
  申请人：JD BIOSCIENCE INC

  公开号：WO2021086133A1

  公开（公告）日：2021-05-06

  본 발명의 화학식 1로 표시되는 삼환식 유도체 또는 이의 약학적으로 허용가능한 염인 화합물은 세로토닌 활성을 저해하는 효과가 우수하므로, 이를 포함하는 약학적 조성물은 세로토닌 활성화와 관련된 대사성 질환 등의 예방 또는 치료에 유용하게 사용될 수 있다.
• Novel tricyclic aminoacetyl and sulfonamide inhibitors of Ras farnesyl protein transferase
  作者：F.George Njoroge、Bancha Vibulbhan、Carmen S. Alvarez、W.Robert Bishop、Joanne Petrin、Ronald J. Doll、V. Girijavallabhan、Ashit K. Ganguly

  DOI：10.1016/s0960-894x(96)00558-6

  日期：1996.12

  Novel tricyclic FPT inhibitors with submicromolar FPT activity are described. Greatly enhanced FPT activity is realized with phthaloyl derivatized amino compound 2k, which showed FPT inhibitory activity of IC50 = 0.66 mu M. Sulfonamides 5g and 50 were also found to be potent FPT inhibitor. SAR resulting from a variety of tricyclic amino acids and sulfonamide derivatives is discussed. Copyright (C) 1996 Elsevier Science Ltd