tert-Butyl (E)-3-{8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-2-[(4-methylphenyl)-sulfonyl]oxy-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-2-propenate | 475058-42-5

• 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: tert-Butyl (E)-3-{8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-2-[(4-methylphenyl)-sulfonyl]oxy-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-2-propenate
• 英文别名: tert-butyl (E)-3-[2-(4-methylphenyl)sulfonyloxy-4-oxo-8-[2-(4-propan-2-yl-1,3-thiazol-2-yl)ethyl]pyrido[1,2-a]pyrimidin-3-yl]prop-2-enoate
• CAS: 475058-42-5
• 化学式: C₃₀H₃₃N₃O₆S₂
• 分子量: 595.741
• InChiKey: SWCGWNHDBMTXEY-WYMLVPIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  152
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-Butyl (E)-3-{8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-2-[(4-methylphenyl)-sulfonyl]oxy-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-2-propenate 在 盐酸 、 TEA 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (E)-3-{8-[2-(4-Isopropyl-1,3-thiazol-2-yl)ethyl]-2-morpholino-4-oxo-4H-pyrido-[1,2-a]pyrimidin-3-yl}-2-propenoic acid
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3: Optimization of potency in the pyridopyrimidine series through the application of a pharmacophore model

  摘要：

  The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM specific efflux pump inhibitors was explored. As predicted by a pharmacophore model, the incorporation substituents at the 2-position improved potency. Piperidines were found to be optimal, and further introduction of polar groups without compromising the activity was shown to be feasible. Careful positioning of the essential acidic moiety of the pharmacophore relative to the scaffold led to the discovery of vinyl tetrazoles with still greater potency. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.060
• 作为产物：
  描述：

  (叔丁氧基羰基亚甲基)三苯基磷烷 、 对甲苯磺酰氯 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 生成 tert-Butyl (E)-3-{8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-2-[(4-methylphenyl)-sulfonyl]oxy-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-2-propenate
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3: Optimization of potency in the pyridopyrimidine series through the application of a pharmacophore model

  摘要：

  The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM specific efflux pump inhibitors was explored. As predicted by a pharmacophore model, the incorporation substituents at the 2-position improved potency. Piperidines were found to be optimal, and further introduction of polar groups without compromising the activity was shown to be feasible. Careful positioning of the essential acidic moiety of the pharmacophore relative to the scaffold led to the discovery of vinyl tetrazoles with still greater potency. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.060

文献信息

• Drug efflux pump inhibitor
  申请人：DAIICHI PHARMACEUTICAL CO., LTD

  公开号：US20030092720A1

  公开（公告）日：2003-05-15

  A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): 1 wherein, R 1 and R 2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W 1 represents —CH═CH—, —CH 2 O—, —CH 2 CH 2 — or the like; R 3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R 4 represents hydrogen atom, a group of —OZ 0-4 R 5 (Z 0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R 5 represents a cyclic alkyl group, an aryl group or the like); W 2 represents a single bond or —C(R 8 )═C(R 9 )— (R 8 and R 9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W 2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.

  一种用于预防和/或治疗微生物感染的药物，其活性成分表示为以下一般式(I)的化合物： 其中，R1和R2代表氢原子、卤素原子、羟基或类似物，W1代表—CH═CH—、—CH2O—、—CH2CH2—或类似物；R3代表氢原子、卤素原子、羟基或氨基；R4代表氢原子、—OZ0-4R5（Z0-4代表烷基链、氟取代的烷基链或单键，R5代表环烷基、芳基或类似物）；W2代表单键或—C(R8)═C(R9)—（R8和R9代表氢原子、卤素原子、较低烷基或类似物，Q代表酸性基团，但W2和Q可以共同形成乙烯基噻唑二酮或等效的杂环环；m和n代表0到2的整数，q代表0到3的整数。
• MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 3: Optimization of potency in the pyridopyrimidine series through the application of a pharmacophore model
  作者：Kiyoshi Nakayama、Haruko Kawato、Jun Watanabe、Masami Ohtsuka、Ken-ichi Yoshida、Yoshihiro Yokomizo、Atsunobu Sakamoto、Noriko Kuru、Toshiharu Ohta、Kazuki Hoshino、Kumi Yoshida、Hiroko Ishida、Aesop Cho、Monica H. Palme、Jason Z. Zhang、Ving J. Lee、William J. Watkins

  DOI：10.1016/j.bmcl.2003.10.060

  日期：2004.1

  The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM specific efflux pump inhibitors was explored. As predicted by a pharmacophore model, the incorporation substituents at the 2-position improved potency. Piperidines were found to be optimal, and further introduction of polar groups without compromising the activity was shown to be feasible. Careful positioning of the essential acidic moiety of the pharmacophore relative to the scaffold led to the discovery of vinyl tetrazoles with still greater potency. (C) 2003 Elsevier Ltd. All rights reserved.