N¹-((2,5-dimethyloxazol-4-yl)methyl)-N³-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-methoxyphenyl)sulfonamido)-1-phenylbutan-2-yl)-N¹-methyl-5-(methylamino)isophthalamide | 1203560-50-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N¹-((2,5-dimethyloxazol-4-yl)methyl)-N³-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-methoxyphenyl)sulfonamido)-1-phenylbutan-2-yl)-N¹-methyl-5-(methylamino)isophthalamide
• 英文别名: N1-[(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl-(4-methoxyphenyl)sulfonyl-amino]propyl]-N3-[(2,5-dimethyloxazol-4-yl)methyl]-N3-methyl-5-(methylamino)benzene-1,3-dicarboxamide；3-N-[(2,5-dimethyl-1,3-oxazol-4-yl)methyl]-1-N-[(2S,3R)-3-hydroxy-4-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]-1-phenylbutan-2-yl]-3-N-methyl-5-(methylamino)benzene-1,3-dicarboxamide
• CAS: 1203560-50-2
• 化学式: C₃₇H₄₇N₅O₇S
• 分子量: 705.875
• InChiKey: NKUCLDPJMBMPKV-QWOOXDRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  50
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (2,5-二甲基-1,3-噁唑-4-基)甲胺 在 lithium hydroxide monohydrate 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 mineral oil 为溶剂， 反应 35.0h， 生成 N¹-((2,5-dimethyloxazol-4-yl)methyl)-N³-((2S,3R)-3-hydroxy-4-((N-isobutyl-4-methoxyphenyl)sulfonamido)-1-phenylbutan-2-yl)-N¹-methyl-5-(methylamino)isophthalamide
  参考文献：
  名称：

  Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

  摘要：

  Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme K-i of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 angstrom resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 angstrom resolution. These structures revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.005

文献信息

• NONPEPTIDE HIV-1 PROTEASE INHIBITORS
  申请人：Ghosh Arun K.

  公开号：US20110178123A1

  公开（公告）日：2011-07-21

  Novel compounds and compositions for treating patients in need of relief from HIV, AIDS, and AIDS-related diseases are described. Methods for treating HIV, AIDS, and AIDS-related diseases using the compounds described herein are also described.
• US8791135B2
  申请人：——

  公开号：US8791135B2

  公开（公告）日：2014-07-29
• US9085571B2
  申请人：——

  公开号：US9085571B2

  公开（公告）日：2015-07-21
• Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex
  作者：Arun K. Ghosh、Margherita Brindisi、Prasanth R. Nyalapatla、Jun Takayama、Jean-Rene Ella-Menye、Sofiya Yashchuk、Johnson Agniswamy、Yuan-Fang Wang、Manabu Aoki、Masayuki Amano、Irene T. Weber、Hiroaki Mitsuya

  DOI：10.1016/j.bmc.2017.04.005

  日期：2017.10

  Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme K-i of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 angstrom resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 angstrom resolution. These structures revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site. (C) 2017 Elsevier Ltd. All rights reserved.