S-(1-(4-fluorophenyl)-3-oxopropan-2-yl) 3-(benzyloxy)-9-bromo-7-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carbothioate | 1251462-17-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: S-(1-(4-fluorophenyl)-3-oxopropan-2-yl) 3-(benzyloxy)-9-bromo-7-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carbothioate
• CAS: 1251462-17-5
• 化学式: C₂₉H₂₅BrFN₃O₅S
• 分子量: 626.503
• InChiKey: NTISFXWUSDVTNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  90.21
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  S-(1-(4-fluorophenyl)-3-oxopropan-2-yl) 3-(benzyloxy)-9-bromo-7-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carbothioate 在 ammonium acetate 、 溶剂黄146 作用下， 生成 3-benzyloxy-9-bromo-2-[5-(4-fluoro-benzyl)-thiazol-2-yl]-7-morpholin-4-yl-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

  摘要：

  A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.041
• 作为产物：
  描述：

  2-bromo-3-(4-fluorophenyl)propanal 、 3-benzyloxy-9-bromo-7-morpholin-4-yl-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carboxylic acid 在 sodium hydrogensulfide 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 生成 S-(1-(4-fluorophenyl)-3-oxopropan-2-yl) 3-(benzyloxy)-9-bromo-7-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carbothioate
  参考文献：
  名称：

  Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

  摘要：

  A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.041

文献信息

• Design of a series of bicyclic HIV-1 integrase inhibitors. Part 2: Azoles: Effective metal chelators
  作者：Giang Le、Nick Vandegraaff、David I. Rhodes、Eric D. Jones、Jonathan A.V. Coates、Neeranat Thienthong、Lisa J. Winfield、Long Lu、Xinming Li、Changjiang Yu、Xiao Feng、John J. Deadman

  DOI：10.1016/j.bmcl.2010.07.081

  日期：2010.10

  Synthesis of a diverse set of azoles and their utilizations as an amide isostere in the design of HIV integrase inhibitors is described. The Letter identified thiazole, oxazole, and imidazole as the most promising heterocycles. Initial SAR studies indicated that these novel series of integrase inhibitors are amenable to lead optimization. Several compounds with low nanomolar inhibitory potency are reported

  描述了多种唑类化合物的合成及其在HIV整合酶抑制剂设计中作为酰胺等排物的用途。该信确认噻唑，恶唑和咪唑是最有前途的杂环。最初的SAR研究表明，这些新颖的整合酶抑制剂系列适合进行优化。报道了几种具有低纳摩尔抑制力的化合物。