6-(2-Bromo-phenyl)-2-hydroxy-4-oxo-hex-2-enoic Acid Methyl Ester

• 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: 6-(2-Bromo-phenyl)-2-hydroxy-4-oxo-hex-2-enoic Acid Methyl Ester
• 英文别名: methyl (Z)-6-(2-bromophenyl)-2-hydroxy-4-oxohex-2-enoate
• 化学式: C₁₃H₁₃BrO₄
• 分子量: 313.148
• InChiKey: AWORBHPSEMYQOG-WQLSENKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(2-Bromo-phenyl)-2-hydroxy-4-oxo-hex-2-enoic Acid Methyl Ester 生成 (Z)-6-(2-bromophenyl)-2-hydroxy-4-oxohex-2-enoic acid
  参考文献：
  名称：

  Triketoacid inhibitors of HIV-integrase: A new chemotype useful for probing the integrase pharmacophore

  摘要：

  Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. This study reports on the discovery of a new triketoacid-based chemotype that selectively inhibits the strand transfer reaction of HIV-integrase. SAR studies showed that the template binds to integrase in a manner similar to the diketoacid-based inhibitors. Moreover, comparison of the new chemotype to two different diketoacid templates led us to propose two aryl-binding domains in the inhibitor binding site. This information was used to design a new diketoacid template with improved activity against the enzyme. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.010
• 作为产物：
  描述：

  2-乙酰基-3-(2-溴苯基)丙酸乙酯 在 二甲基亚砜 、 sodium chloride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 6-(2-Bromo-phenyl)-2-hydroxy-4-oxo-hex-2-enoic Acid Methyl Ester
  参考文献：
  名称：

  Triketoacid inhibitors of HIV-integrase: A new chemotype useful for probing the integrase pharmacophore

  摘要：

  Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. This study reports on the discovery of a new triketoacid-based chemotype that selectively inhibits the strand transfer reaction of HIV-integrase. SAR studies showed that the template binds to integrase in a manner similar to the diketoacid-based inhibitors. Moreover, comparison of the new chemotype to two different diketoacid templates led us to propose two aryl-binding domains in the inhibitor binding site. This information was used to design a new diketoacid template with improved activity against the enzyme. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.010

文献信息

• HIV integrase inhibitors
  申请人：——

  公开号：US20020123527A1

  公开（公告）日：2002-09-05

  The present invention relates to the inhibition of HIV integrase, and to the treatment of AIDS or ARC by administering compounds of the following formula, or a tautomer of said compound, or a pharmaceutically acceptable salt, solvate or prodrug of said compound or of a tautomer thereof. 1 wherein R 1 is phenyl, wherein said phenyl is substituted from 1-3 times with R 2 , or R 1 naphthyl, and wherein said naphthyl is optionally substituted from 1-3 times with R2; each R 2 is independently selected from halo, C 1 -C 3 alkyl, C 1 -C 2 alkoxy, C 1 -C 3 haloalkyl, and phenyl-(CH 2 ) m O n —; m is 0 or 1; n is 0 or 1; and Z is methylene or —C(O)—, provided that when Z is —C(O)— said substituted phenyl is not ortho-chloro phenyl.

  本发明涉及抑制HIV整合酶，并通过给予以下结构的化合物、该化合物的互变异构体、药学上可接受的盐、溶剂合物或前药的治疗，来治疗艾滋病或ARC。其中R1为苯基，其中所述苯基被R2取代1-3次，或者R1为萘基，其中所述萘基可以选择被R2取代1-3次；每个R2独立地选择自卤素、C1-C3烷基、C1-C2烷氧基、C1-C3卤代烷基和苯基-(CH2)mOn—；m为0或1；n为0或1；Z为亚甲基或—C(O)—，条件是当Z为—C(O)—时，所述取代的苯基不是邻氯苯基。
• HIV INTEGRASE INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1370510A2

  公开（公告）日：2003-12-17
• US6548546B2
  申请人：——

  公开号：US6548546B2

  公开（公告）日：2003-04-15
• [EN] HIV INTEGRASE INHIBITORS<br/>[FR] INHIBITEURS D'INTEGRASE DU VIH
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2001098248A2

  公开（公告）日：2001-12-27

  The present invention relates to the inhibition of HIV integrase, and to the treatment of AIDS or ARC by administering compounds of the formula (I), or a tautomer of said compound, or a pharmaceutically acceptable salt, solvate or prodrug of said compound or of a tautomer thereof, wherein R1 is phenyl, wherein said phenyl is substituted from 1-3 times with R?2, or R1¿ naphthyl, and wherein said naphthyl is optionally substituted from 1-3 times with R2; each R2 is independently selected from halo, C¿1?-C3 alkyl, C1-C2 alkoxy, C1-C3 haloalkyl, and phenyl-(CH2)mOn-; m is 0 or 1; n is 0 or 1; and Z is methylene or -C(O)-, provided that when Z is -C(O)- said substituted phenyl is not ortho-chloro phenyl.
• Triketoacid inhibitors of HIV-integrase: A new chemotype useful for probing the integrase pharmacophore
  作者：Michael A. Walker、Timothy Johnson、Zhuping Ma、Jacques Banville、Roger Remillard、Oak Kim、Yunhui Zhang、Andrew Staab、Henry Wong、Albert Torri、Himadri Samanta、Zeyu Lin、Carol Deminie、Brian Terry、Mark Krystal、Nicholas Meanwell

  DOI：10.1016/j.bmcl.2006.03.010

  日期：2006.6

  Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. This study reports on the discovery of a new triketoacid-based chemotype that selectively inhibits the strand transfer reaction of HIV-integrase. SAR studies showed that the template binds to integrase in a manner similar to the diketoacid-based inhibitors. Moreover, comparison of the new chemotype to two different diketoacid templates led us to propose two aryl-binding domains in the inhibitor binding site. This information was used to design a new diketoacid template with improved activity against the enzyme. (c) 2006 Elsevier Ltd. All rights reserved.