Ethyl 2-[3-(3-fluorophenyl)prop-2-ynoyl-methylamino]acetate | 406687-60-3

• 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: Ethyl 2-[3-(3-fluorophenyl)prop-2-ynoyl-methylamino]acetate
• CAS: 406687-60-3
• 化学式: C₁₄H₁₄FNO₃
• 分子量: 263.268
• InChiKey: PLRLLQJXUUZCDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 2-[3-(3-fluorophenyl)prop-2-ynoyl-methylamino]acetate 在 palladium on activated charcoal 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 3-(3-Fluoro-phenyl)-1-methyl-5-oxo-pyrrolidine-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  4,5-Disubstituted cis-pyrrolidinones as inhibitors of 17β-hydroxysteroid dehydrogenase II. Part 1: Synthetic approach

  摘要：

  17beta-Hydroxysteroid dehydrogenase II (17beta-HSD II) antagonists may provide an important way into preventing the onset of osteoporosis. The discovery of 4,5-disubstituted eis-pyrrolidinones as 17beta-HSD II inhibitors led to the development of an efficient intramolecular Michael addition, followed by catalytic hydrogenation to obtain the desired cis configuration. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.01.003
• 作为产物：
  描述：

  3-(3-fluorophenyl)propiolic acid 、 肌氨酸乙酯盐酸盐 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 Ethyl 2-[3-(3-fluorophenyl)prop-2-ynoyl-methylamino]acetate
  参考文献：
  名称：

  4,5-二取代的顺式-吡咯烷酮类作为II型17β-羟基类固醇脱氢酶的抑制剂。第3部分。确定主要候选人。

  摘要：

  研究了一系列4,5-二取代的顺式-吡咯烷酮作为17β-HSDII抑制剂，用于治疗骨质疏松症。给出了几种化合物的生化数据。选择化合物42作为主要候选化合物。

  DOI：

  10.1016/j.bmcl.2006.06.041

文献信息

• 17-Beta-hydroxysteroid dehydrogenase-II inhibitors
  申请人：——

  公开号：US20030087952A1

  公开（公告）日：2003-05-08

  17-beta-hydroxysteroid dehydrogenase-I1 inhibitors having the structural formula 1 wherein the phenyl group labeled A and the group —C(R 4 )(R 6 )Y are oriented cis to each other; W represents 0 or S; R 1 represents —H or optionally substituted —(C 1 -C 4 )alkyl; n represents 0 or an integer of 1-3; and R 2 represents any of a variety of substituents on ring A. R 4 generally represents —H but may be a bond terminating at the ortho position of ring A. Y represents fluorine, —OR 5 , or —SR 5 , and R 5 represents —H. optionally substituted —(C 1 -C 4 )alkyl, optionally substituted -phenyl, optionally substituted —(C 1 -C 4 )alkyl-phenyl, or optionally substituted —(C 1 -C 4 )acyl. R 6 represents any of a variety of groups as defined in the specification and claims, including heteroaryl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, alkynyl, arylalkynyl, heteroarylalkynyl, aryl, and indolyl. Pharmaceutically acceptable salts and N-oxides of these materials are also included. Also claimed are pharmaceutical compositions containing these materials and methods of using them.

  17-beta-羟基类固醇脱氢酶I1抑制剂具有结构式1，其中苯基A和基团—C(R4)(R6)Y相对取向；W代表0或S；R1代表—H或可选择取代的—(C1-C4)烷基；n代表0或1-3的整数；R2代表环A上的各种取代基之一。R4通常代表—H，但可能是终止在环A的邻位的键。Y代表氟、—OR5或—SR5，R5代表—H、可选择取代的—(C1-C4)烷基、可选择取代的苯基、可选择取代的—(C1-C4)烷基-苯基或可选择取代的—(C1-C4)酰基。R6代表根据说明书和索赔中定义的各种基团之一，包括杂芳基、芳基烷基、杂芳基烷基、芳基烯基、杂芳基烯基、炔基、芳基炔基、杂芳基炔基、芳基和吲哚基。还包括这些物质的药用合适盐和N-氧化物。还声明包含这些物质的药物组合物和使用它们的方法。
• 17-BETA-HYDROXYSTEROID DEHYDROGENASE-II INHIBITORS
  申请人：Bayer Pharmaceuticals Corporation

  公开号：EP1326829A2

  公开（公告）日：2003-07-16
• US6784167B2
  申请人：——

  公开号：US6784167B2

  公开（公告）日：2004-08-31
• [EN] 17-BETA-HYDROXYSTEROID DEHYDROGENASE-II INHIBITORS<br/>[FR] INHIBITEURS DE 17-BETA-HYDROXYSTEROIDE DESHYDROGENASE II
  申请人：BAYER AG

  公开号：WO2002026706A2

  公开（公告）日：2002-04-04

  17-beta-hydroxysteroid dehydrogenase-II inhibitors having the structural formula (I) wherein the phenyl group labeled A and the group -C(R4)(R6)Y are oriented cis to each other; W represents O or S; R1 represents -H or optionally substituted -(C¿1?-C4)alkyl; n represents 0 or an integer of 1-3; and R?2¿ represents any of a variety of substituents on ring A. R4 generally represents -H but may be a bond terminating at the ortho position of ring A. Y represents fluorine, -OR5, or -SR5 , and R5 represents -H, optionally substituted -(C¿1?-C4)alkyl, optionally substituted -phenyl, optionally substituted -(C1-C4)alkyl-phenyl, or optionally substituted -(C1-C4)acyl. R?6¿ represents any of a variety of groups as defined in the specification and claims, including heteroaryl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, alkynyl, arylalkynyl, heteroarylalkynyl, aryl, and indolyl. Pharmaceutically acceptable salts and N-oxides of these materials are also included. Also claimed are pharmaceutical compositions containing these materials and methods of using them.
• 4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17β-hydroxysteroid dehydrogenase. Part 3. Identification of lead candidate
  作者：Jill Wood、Cedo M. Bagi、Christiana Akuche、Antonietta Bacchiocchi、Jeremy Baryza、Marie-Luise Blue、Catherine Brennan、Ann-Marie Campbell、Soongyu Choi、James H. Cook、Patricia Conrad、Brian R. Dixon、Paul P. Ehrlich、Todd Gane、David Gunn、Ted Joe、Jeffrey S. Johnson、Jerold Jordan、Richard Kramss、Peiying Liu、Joan Levy、Derek B. Lowe、Ian McAlexander、Reina Natero、Anikó M. Redman、William J. Scott、Christopher Town、Ming Wang、Yamin Wang、Zhonghua Zhang

  DOI：10.1016/j.bmcl.2006.06.041

  日期：2006.9

  A series of 4,5-disubstituted cis-pyrrolidinones was investigated as inhibitors of 17beta-HSD II for the treatment of osteoporosis. Biochemical data for several compounds are given. Compound 42 was selected as the lead candidate.

  研究了一系列4,5-二取代的顺式-吡咯烷酮作为17β-HSDII抑制剂，用于治疗骨质疏松症。给出了几种化合物的生化数据。选择化合物42作为主要候选化合物。