5-tert-butoxycarbonylamino-3-methanesulfonyl-isothiazole-4-carboxylic acid methyl ester | 651305-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-tert-butoxycarbonylamino-3-methanesulfonyl-isothiazole-4-carboxylic acid methyl ester
• 英文别名: 5-tert-butoxycarbonylamino-3-methanesulfonylisothiazole-4-carboxylic acid methyl ester；methyl 5-[(2-methylpropan-2-yl)oxycarbonylamino]-3-methylsulfonyl-1,2-thiazole-4-carboxylate
• CAS: 651305-82-7
• 化学式: C₁₁H₁₆N₂O₆S₂
• 分子量: 336.39
• InChiKey: VKABKZBKILGLLH-UHFFFAOYSA-N

物化性质

• 沸点：
  416.1±45.0 °C(Predicted)
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  148
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-tert-butoxycarbonylamino-3-methanesulfonyl-isothiazole-4-carboxylic acid methyl ester 在 正丁基锂 、 tris(dibenzylideneacetone)dipalladium (0) 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 3-(4-Chloro-benzylsulfanyl)-5-(pyrimidin-4-ylamino)-isothiazole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of novel isothiazole inhibitors of the TrkA kinase: Structure–activity relationship, computer modeling, optimization, and identification of highly potent antagonists

  摘要：

  The design, synthesis, and biological evaluation of potent inhibitors of the TrkA kinase is presented. A homology model is created to aid in the enhancement of potency and selectivity of isothiazole inhibitors found during a high-throughput screen. Three different syntheses are utilized to make diverse analogs within this series. Aminoheterocycles are found to be good urea surrogates, whereas bicyclic substituents on the C3 thio group were found to be extremely potent TrkA inhibitors in kinase and cell assays. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.003
• 作为产物：
  描述：

  3,5-双(甲基硫代)异噻唑-4-甲腈 在 Oxone 、 硫酸 、 氨 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 5-tert-butoxycarbonylamino-3-methanesulfonyl-isothiazole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of novel isothiazole inhibitors of the TrkA kinase: Structure–activity relationship, computer modeling, optimization, and identification of highly potent antagonists

  摘要：

  The design, synthesis, and biological evaluation of potent inhibitors of the TrkA kinase is presented. A homology model is created to aid in the enhancement of potency and selectivity of isothiazole inhibitors found during a high-throughput screen. Three different syntheses are utilized to make diverse analogs within this series. Aminoheterocycles are found to be good urea surrogates, whereas bicyclic substituents on the C3 thio group were found to be extremely potent TrkA inhibitors in kinase and cell assays. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.003

文献信息

• [EN] ISOTHIAZOLE DERIVATIVES USEFUL AS ANTICANCER AGENTS<br/>[FR] DERIVES ISOTHIAZOLES UTILES EN TANT QU'AGENTS ANTICANCEREUX
  申请人：PFIZER PROD INC

  公开号：WO2004011461A1

  公开（公告）日：2004-02-05

  The invention relates to compounds of the formula 1 or pharmaceutically acceptable salts, prodrugs, solvates or hydrates thereof, wherein X, R1, and R2 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of treating hyperproliferative disorders disorders in a mammal by administering the compounds of formula 1.

  该发明涉及公式1的化合物或药学上可接受的盐、前药、溶剂合物或水合物，其中X、R1和R2的定义如本文所述。该发明还涉及含有公式1化合物的药物组合物，并通过给予公式1化合物来治疗哺乳动物的过度增殖性疾病的方法。
• Isothiazole derivatives useful as anticancer agents
  申请人：Pfizer Inc

  公开号：US20040152691A1

  公开（公告）日：2004-08-05

  The invention relates to compounds of the formula 1 1 or pharmaceutically acceptable salts, prodrugs, solvates or hydrates thereof, wherein wherein X, R 1 , and R 2 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula 1.

  本发明涉及公式11化合物或其药学上可接受的盐、前药、溶剂或水合物，其中X、R1和R2的定义如本文所述。本发明还涉及包含公式1化合物的制药组合物以及通过给予公式1化合物治疗哺乳动物的增殖过度性疾病的方法。
• ISOTHIAZOLE DERIVATIVES USEFUL AS ANTICANCER AGENTS
  申请人：Pfizer Products Inc.

  公开号：EP1527071A1

  公开（公告）日：2005-05-04
• US7276602B2
  申请人：——

  公开号：US7276602B2

  公开（公告）日：2007-10-02
• Discovery of novel isothiazole inhibitors of the TrkA kinase: Structure–activity relationship, computer modeling, optimization, and identification of highly potent antagonists
  作者：Blaise Lippa、Joel Morris、Matthew Corbett、Tricia A. Kwan、Mark C. Noe、Sheri L. Snow、Thomas G. Gant、Melchiorra Mangiaracina、Heather A. Coffey、Barbara Foster、Elisabeth A. Knauth、Matthew D. Wessel

  DOI：10.1016/j.bmcl.2006.04.003

  日期：2006.7

  The design, synthesis, and biological evaluation of potent inhibitors of the TrkA kinase is presented. A homology model is created to aid in the enhancement of potency and selectivity of isothiazole inhibitors found during a high-throughput screen. Three different syntheses are utilized to make diverse analogs within this series. Aminoheterocycles are found to be good urea surrogates, whereas bicyclic substituents on the C3 thio group were found to be extremely potent TrkA inhibitors in kinase and cell assays. (c) 2006 Elsevier Ltd. All rights reserved.