(R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | 186538-15-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• 英文别名: (R)-N-(2-methylbenzyl)-3-<(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl>-5,5-dimethyl-1,3-thiazolidine-4-carboxamide；(R)-N-(2-methylbenzyl)-3-{(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide；(4R)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-N-[(2-methylphenyl)methyl]-1,3-thiazolidine-4-carboxamide
• CAS: 186538-15-8
• 化学式: C₂₄H₃₁N₃O₃S
• 分子量: 441.594
• InChiKey: PICJIGSFLXCJMT-PCCBWWKXSA-N

物化性质

• 熔点：
  205-208 °C
• 沸点：
  732.3±60.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 在 sodium hydroxide 、 三乙胺 、 二苯基次膦酰氯 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 (4R)-3-{(2S,3S)-2-羟基-3-[(3-羟基-2-甲基苯甲酰)氨基]-4-苯基丁酰}-5,5-二甲基-N-(2-甲基苯甲基)-1,3-噻唑烷-4-甲酰胺
  参考文献：
  名称：

  含有别苯基去甲他汀的小型HIV蛋白酶抑制剂的构效关系。

  摘要：

  我们设计并合成了一种新型的拟肽类人免疫缺陷病毒（HIV）蛋白酶抑制剂，其中含有独特的非天然氨基酸，别苯去甲他汀[Apns; （2S，3S）-3-氨基-2-羟基-4-苯基丁酸]，其中的羟甲基羰基（HMC）异构体为活性部分。对HIV蛋白酶抑制，抗HIV活性和药代动力学特征的结构活性关系的系统评价导致了一系列结构特征的描述，这些结构特征似乎提供了可口服的HIV蛋白酶抑制剂。最佳结构，以21f（JE-2147）为例，其中并入3-羟基-2-甲基苯甲酰基作为P2配体，在（R）-5,5-二甲基-1,3-噻唑烷-4-羰基（Dmt）残基处引入P1'位点和2-甲基苄基羧酰胺基团作为P2'配体。

  DOI：

  10.1021/jm980637h
• 作为产物：
  描述：

  9H-fluoren-9-ylmethyl N-[(2S,3S)-4-[(4R)-5,5-dimethyl-4-[(2-methylphenyl)methylcarbamoyl]-1,3-thiazolidin-3-yl]-3-hydroxy-4-oxo-1-phenylbutan-2-yl]carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
  参考文献：
  名称：

  Truncation and non-natural amino acid substitution studies on HTLV-I protease hexapeptidic inhibitors

  摘要：

  The culprit behind adult T-cell leukemia, myelopathy/tropical paraparesis, and a plethora of inflammatory diseases is the human T-cell leukemia virus type 1 (HTLV-1). We recently unveiled a potent hexapeptidic HTLV-1 protease inhibitor, KNI-10166, composed mostly of natural amino acid residues. Herein, we report the derivation of potent tetrapeptidic inhibitor KNI-10516, possessing only non-natural amino acid residues. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.066

文献信息

• HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US20040204591A1

  公开（公告）日：2004-10-14

  The present invention concerns processes for preparing compounds of formula (I-H), or a prodrug, pharmaceutically active metabolite, or pharmaceutically active salt or solvate thereof, 1 which are useful as inhibitors of the HIV protease enzyme.

  本发明涉及制备式(I-H)化合物的过程，或其前药、药理活性代谢物、药理活性盐或溶剂化合物的过程，这些化合物可用作HIV蛋白酶酶抑制剂。
• Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands
  作者：Arun K. Ghosh、Sandra Gemma、Elena Simoni、Abigail Baldridge、D. Eric Walters、Kazuhiko Ide、Yasushi Tojo、Yasuhiro Koh、Masayuki Amano、Hiroaki Mitsuya

  DOI：10.1016/j.bmcl.2009.11.123

  日期：2010.2

  A series of stereochemically defined cyclic ethers as P2-ligands were incorporated in an allophenylnorstatine-based isostere to provide a new series of HIV-1 protease inhibitors. Inhibitors 3b and 3c, containing conformationally constrained cyclic ethers, displayed impressive enzymatic and antiviral properties and represent promising lead compounds for further optimization.

  将一系列立体化学定义的环醚作为 P2 配体并入基于别苯去甲司他汀的等排体中，以提供一系列新的 HIV-1 蛋白酶抑制剂。抑制剂3b和3c含有构象受限的环醚，显示出令人印象深刻的酶促和抗病毒特性，并代表了有前途的先导化合物进行进一步优化。
• HIV protease inhibitors, compositions containing the same, their pharmaceutical uses, material for their synthesis
  申请人：Pfizer Inc

  公开号：US20040171842A1

  公开（公告）日：2004-09-02

  Compounds of the formula: 1 where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the HIV protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with the HIV virus. Intermediates and synthetic methods for preparing such compounds are also described.

  揭示了具有以下公式的化合物：1，其中公式变量如本文所定义，这些化合物有利地抑制或阻断HIV蛋白酶的生物活性。这些化合物以及含有这些化合物的药物组合物对治疗感染HIV病毒的患者或宿主是有用的。还描述了制备这些化合物的中间体和合成方法。
• HIV PROTEASE INHIBITORS, COMPOSITIONS CONTAINING THE SAME, THEIR PHARMACEUTICAL USES, MATERIALS FOR THEIR SYNTHESIS
  申请人：Kucera John David

  公开号：US20070066664A1

  公开（公告）日：2007-03-22

  Compounds of the formula: where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the HIV protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with the HIV virus. Intermediates and synthetic methods for preparing such compounds are also described.

  本文披露了以下公式的化合物：其中公式变量如本文所定义，有利地抑制或阻断HIV蛋白酶的生物活性。这些化合物以及含有这些化合物的药物组合物，对于治疗感染HIV病毒的患者或宿主非常有用。还描述了制备这些化合物的中间体和合成方法。
• Methods of preparing novel dipeptide compounds or pharmaceutically acceptable salts thereof
  申请人：Japan Energy Corporation

  公开号：US06222043B1

  公开（公告）日：2001-04-24

  The present invention provides synthetic methodology to produce novel dipeptide compounds and pharmaceutically acceptable salts thereof which exhibit excellent HIV protease inhibitory activity and excellent bioavailability from digestive tracts. Methods of using the dipeptide compounds and pharmaceutically acceptable salts thereof also are provided. A non-limiting example of a dipeptide compound of the invention has the general formula (IA): where R1 represents a 5-membered or 6-membered monocyclic hydrocarbon group or heterocyclic group wherein 3 or fewer substituents other than hydrogen are present on the cyclic group; R21 and R22 each represents a hydrogen atom or a linear or branched aliphatic hydrocarbon group having 1-6 carbon atoms; and R3 represents a linear or branched aliphatic hydrocarbon group having 1-6 carbon atoms or a monovalent group comprising an aromatic monocyclic hydrocarbon group having 12 or fewer carbon atoms in total, wherein a halogen atom can be substituted on the aromatic ring of the aromatic monocyclic hydrocarbon group.

  本发明提供一种合成方法，用于生产新型二肽化合物及其药学上可接受的盐，这些化合物在消化道中表现出优异的HIV蛋白酶抑制活性和优异的生物利用度。本发明还提供了使用这些二肽化合物及其药学上可接受的盐的方法。本发明的一个非限制性例子的二肽化合物具有通式（IA）：其中，R1代表一个5-或6-成员的单环烃基或杂环基，其中除氢之外在环上存在3个或更少的取代基；R21和R22分别代表氢原子或具有1-6个碳原子的线性或支链脂肪烃基；R3代表具有1-6个碳原子的线性或支链脂肪烃基或仅包含12个或更少碳原子的芳香单环烃基的一价基团，其中卤原子可以取代芳香单环烃基的芳香环。