1,4-dihydro-4-(3-isocyanatophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid dimethyl ester | 182621-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1,4-dihydro-4-(3-isocyanatophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid dimethyl ester
• 英文别名: Dimethyl 4-(3-isocyanatophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 182621-24-5
• 化学式: C₁₈H₁₈N₂O₅
• 分子量: 342.351
• InChiKey: GBRXSCKPIPOWMD-UHFFFAOYSA-N

物化性质

• 沸点：
  471.8±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  94.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,4-dihydro-4-(3-isocyanatophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid dimethyl ester 以 二氯甲烷 为溶剂， 以65%的产率得到1,4Dihydro-2,6-dimethyl-4-[3-[[[[3-[4-[3-(2-propynyloxy)phenyl]-1-piperidinyl]-propyl]amino]carbonyl]amino]phenyl]-3,5-pyridinedicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Dihydropyridine NPY antagonists: piperidine derivatives

  摘要：

  一系列非肽类NPY拮抗剂已经合成，由Formula I的哌啶和四氢吡啶衍生物以及4-苯基-1,4-二氢吡啶组成。作为NPY诱导的进食行为的拮抗剂，预计这些化合物将作为有效的压食剂，促进减重和治疗进食障碍。

  公开号：

  US05668151A1
• 作为产物：
  描述：

  1,4-dihydro-4-(3-aminophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid,dimethyl ester 以 四氢呋喃 、 甲苯 为溶剂， 反应 48.5h， 生成 1,4-dihydro-4-(3-isocyanatophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Dihydropyridine neuropeptide Y Y 1 receptor antagonists 2

  摘要：

  Structure-activity studies around the urea linkage in BMS-193885 (4a) identified the cyanoguanidine moiety as an effective urea replacement in a series of dihydropyridine NPY Y-1 receptor antagonists. In comparison to urea 4a (K-i = 3.3 nM), cyanoguanidine 20 (BMS-205749) displayed similar binding potency at the Y-1 receptor (K-i = 5.1 nM) and full functional antagonism (K-b = 2.6 nM) in SK-N-MC cells. Cyanoguanidine 20 also demonstrated improved permeability properties in Caco-2 cells in comparison to urea 4a (43 vs 19 nm/s). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.016

文献信息

• Dihydropyridine npy antagonists: piperazine derivatives
  申请人：Bristol-Myers Squibb Company

  公开号：US05635503A1

  公开（公告）日：1997-06-03

  A series of non-peptidergic antagonists of NPY have been synthesized and are comprised of piperazine and homopiperazine derivatives of 4-phenyl-1,4-dihydropyridines of Formula (I). ##STR1## As antagonists of NPY-induced feeding behavior, these compounds are expected to act as effective anorexiant agents in promoting weight loss and treating eating disorders.

  一系列非肽类NPY拮抗剂已经合成，由式(I)的4-苯基-1,4-二氢吡啶的哌嗪和同哌嗪衍生物组成。作为NPY诱导的进食行为的拮抗剂，预计这些化合物将作为有效的压食剂药物，促进减重和治疗进食障碍。
• Dihydropyridine Neuropeptide Y Y1 Receptor Antagonists
  作者：Graham S. Poindexter、Marc A. Bruce、Karen L. LeBoulluec、Ivo Monkovic、Scott W. Martin、Eric M. Parker、Larry G. Iben、Rachel T. McGovern、Astrid A. Ortiz、Jennifer A. Stanley、Gail K. Mattson、Michael Kozlowski、Meredith Arcuri、Ildiko Antal-Zimanyi

  DOI：10.1016/s0960-894x(01)00761-2

  日期：2002.2

  Dihydropyridine 5a was found to be an inhibitor of neuropeptide Y-1 binding in a high throughput I-125-PYY screening assay. Structure-activity studies around certain portions of the dihydropyridine chemotype identified BMS-193885 (6e) as a potent and selective Y-1 receptor antagonist. In a forskolin-stimulated c-AMP production assay using CHO cells expressing the human Y-1 receptor, 6e demonstrated full functional antagonism (K-b = 4.5 nM). Compound 6e inhibited NPY-induced feeding in satiated rats when dosed at 3.0 and 10.0 mg/kg (ip), and also decreased spontaneous overnight food consumption in rats at doses of 10 and 20 mg/kg (ip). (C) 2002 Elsevier Science Ltd. All rights reserved.