methyl 1-acetylsulfanylmethylcyclohexanecarboxylate | 374931-26-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 1-acetylsulfanylmethylcyclohexanecarboxylate
• 英文别名: 1-acetylsulfanylmethylcyclohexanecarboxylic acid methyl ester；methyl 1-(acetylsulfanylmethyl)cyclohexane-1-carboxylate
• CAS: 374931-26-7
• 化学式: C₁₁H₁₈O₃S
• 分子量: 230.328
• InChiKey: ADJFQXQSWGQIPZ-UHFFFAOYSA-N

物化性质

• 沸点：
  303.8±15.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-acetylsulfanylmethylcyclohexanecarboxylate 在 水 、 氯 、 溶剂黄146 作用下， 以90%的产率得到1-chlorosulfonylmethylcyclohexanecarboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species

  摘要：

  Hepatitis is a disease characterized by inflammation of the liver, usually producing swelling and, in many cases, permanent damage to liver tissues. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically 3% of the world's population. Boceprevir, SCH 503034, (1) our first generation HCV inhibitor, has already established proof-of-concept and is currently in late stage (phase III) clinical trials. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P-4 pocket by introducing a new sulfonamide moiety and optimization of the P1/P-1' capping led to the discovery of a novel series of inhibitors of the HCV NS3 serine protease. Optimization of the P-1 residue significantly improved potency and selectivity. The combination of optimal moieties led to the discovery of compound 47 which, in addition to being a potent inhibitor of HCV subgenomic RNA replication, was also found to have good PK profile in rat, dog and monkey. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.044
• 作为产物：
  描述：

  methyl 4-(acetylsulfanylmethyl)tetrahydropyran-4-carboxylate 、 Methyl 1-iodomethylcyclohexanecarboxylate 以to yield the title compound as a brown gum (15 g, 92%)的产率得到methyl 1-acetylsulfanylmethylcyclohexanecarboxylate
  参考文献：
  名称：

  Hydroxamic acid derivatives

  摘要：

  本发明涵盖了一些新型化合物，这些化合物是基质金属蛋白酶、ADAM或ADAM-TS酶的抑制剂，可以用于治疗由这些酶介导的疾病，包括退行性疾病和某些癌症。

  公开号：

  US06787536B2

文献信息

• S_N2-Type Nucleophilic Opening of β-Thiolactones (Thietan-2-ones) as a Source of Thioacids for Coupling Reactions
  作者：David Crich、Kasinath Sana

  DOI：10.1021/jo9001728

  日期：2009.5.1

  3-arylthiopropionamides carrying various substituents in the 2-position. Alternatively, the trapping combination of an electron deficient aryl halide and an amine may be replaced by a 2,4-dinitrobenzenesulfonamide, resulting in the formation of the same products overall with the incorporation of the latent amine in the sulfonamide into the final amide product. In another embodiment, the thiocarboxylate intermediate

  在3位上被烷基和氨基甲酰基单取代的β-硫内酯通过涉及S N的过程被芳硫醇盐进行亲核开环在4位上发生2型攻击，导致在3位上取代了3-芳基硫代丙酸酯。这些硫代羧酸盐可以通过亲山芳烃取代过程由Mukaiyama试剂或Sanger试剂原位捕获，从而导致高度活化的硫酯，然后使它们与伯胺或仲胺进一步反应，总体上导致一锅，三组分合成在2-位带有各种取代基的3-芳基硫代丙酰胺。或者，可用2,4-二硝基苯磺酰胺代替电子不足的芳基卤化物和胺的捕集组合，导致整体形成相同的产物，同时在磺酰胺中掺入潜伏胺到最终的酰胺产物中。在另一个实施例中，N-芳烃磺酰基3-芳基硫代丙酰胺衍生物。
• SULFUR COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE
  申请人：Velazquez Francisco

  公开号：US20070197448A1

  公开（公告）日：2007-08-23

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明揭示了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一种实施方式中，本发明揭示了包含这些化合物的制药组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Sulfur compounds as inhibitors of hepatitis C virus NS3 serine protease
  申请人：Schering Corporation

  公开号：US07816326B2

  公开（公告）日：2010-10-19

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明揭示了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一种实施方式中，本发明揭示了包含这些化合物的药物组合物，以及使用它们用于治疗与HCV蛋白酶相关的疾病的方法。
• HYDROXAMIC ACID DERIVATIVES
  申请人：Darwin Discovery Limited

  公开号：EP1282614B1

  公开（公告）日：2003-11-12
• SULFUR COMPOUNDS AS INHIIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE
  申请人：Schering Corporation

  公开号：EP2134739A2

  公开（公告）日：2009-12-23