KNI-1249 | 478696-75-2

• 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: KNI-1249
• 英文别名: (R)-N-cyclopentyl-3-[(2S,3S)-3-(3-hydroxy-2-methylbenzoyl)amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide；(R)-3-((2S,3S)-2-Hydroxy-3-{[1-(3-hydroxy-2-methyl-phenyl)-methanoyl]-amino}-4-phenyl-butanoyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid cyclopentylamide；(4R)-N-Cyclopentyl-3-{(2S,3S)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide；(4R)-N-cyclopentyl-3-[(2S,3S)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• CAS: 478696-75-2
• 化学式: C₂₉H₃₇N₃O₅S
• 分子量: 539.696
• InChiKey: SQRHLBFIYCCTAD-ZKMPZPQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 KNI-1249
  参考文献：
  名称：

  Small-Sized Human Immunodeficiency Virus Type-1 Protease Inhibitors Containing Allophenylnorstatine to Explore the S₂′ Pocket

  摘要：

  A series of HIV protease inhibitor based on the allophenylnorstatine structure with various P-2' moieties were synthesized. Among these analogues, we discovered that a small allyl group would maintain potent enzyme inhibitory activity compared to the o-methylbenzyl moiety in clinical candidate I (KNI-764, also known as JE-2147, AG-1776, or SM-319777). Introduction of all anilinic amino group to 2 (KNI-727) improved water-solubility and anti-HIV-1 activity, X-ray crystallographic analysis of 13k (KNI-1689) with a beta-methallyl group kit P-2' position revealed hydrophobic interactions with Ala28, Ile84, kind Ile50' similar to that of 1. The presence of an additional methyl group on the allyl group in compound 13k significantly increased anti-HIV activity over 1 while providing a rational drug design for structural minimization and improving membrane permeability.

  DOI：

  10.1021/jm9005115

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。
• HIV PROTEASE INHIBITORS, COMPOSITIONS CONTAINING THE SAME, THEIR PHARMACEUTICAL USES AND MATERIALS FOR THEIR SYNTHESIS
  申请人：Agouron Acquisition Corp.

  公开号：EP1409466A2

  公开（公告）日：2004-04-21
• US7094909B2
  申请人：——

  公开号：US7094909B2

  公开（公告）日：2006-08-22
• US7179918B2
  申请人：——

  公开号：US7179918B2

  公开（公告）日：2007-02-20
• [EN] HIV PROTEASE INHIBITORS, COMPOSITIONS CONTAINING THE SAME, THEIR PHARMACEUTICAL USES AND MATERIALS FOR THEIR SYNTHESIS<br/>[FR] INHIBITEURS DE LA PROTEASE VIH, COMPOSITIONS LES CONTENANT, LEURS UTILISATIONS PHARMACEUTIQUES ET MATERIAUX UTILISES POUR LEUR SYNTHESE
  申请人：AGOURON PHARMA

  公开号：WO2002100844A2

  公开（公告）日：2002-12-19

  Compounds of Formula (I), 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.