ethyl 4-[(2-ethoxycarbonylethyl)(1-propylbutyl)amino]-6-methyl-2-trifluoromethanesulfonyloxynicotinate | 374631-18-2

• 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: ethyl 4-[(2-ethoxycarbonylethyl)(1-propylbutyl)amino]-6-methyl-2-trifluoromethanesulfonyloxynicotinate
• 英文别名: ethyl 4-[(3-ethoxy-3-oxopropyl)-heptan-4-ylamino]-6-methyl-2-(trifluoromethylsulfonyloxy)pyridine-3-carboxylate
• CAS: 374631-18-2
• 化学式: C₂₂H₃₃F₃N₂O₇S
• 分子量: 526.574
• InChiKey: QBJRQWWNMAOSMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  ethyl 4-[(2-ethoxycarbonylethyl)(1-propylbutyl)amino]-6-methyl-2-trifluoromethanesulfonyloxynicotinate 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 生成 5-chloro-7-methyl-1-(1-propylbutyl)-2,3-dihydro-1H-[1,6]naphthyridin-4-one
  参考文献：
  名称：

  Potent, Orally Active Corticotropin-Releasing Factor Receptor-1 Antagonists Containing a Tricyclic Pyrrolopyridine or Pyrazolopyridine Core

  摘要：

  Two new classes of tricyclic-based corticotropin-releasing factor (CRF1) receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based molecules 19g and 22a, respectively, were discovered that potently bind the recombinant CRF1 receptor (K-i = 3.5, 2.9 nM) and inhibit adrenocorticotropic hormone (ACTH) release from rat pituitary cell culture (IC50 = 14, 6.8 nM). These compounds show good oral bioavailabity (F = 24%, 7.0%) and serum half-lives in rats (t(1/2) = 6.3, 12 h) and penetrate the rat brain ([brain]/[plasma] = 0.27, 0.52) but tend toward large volumes of distribution (V-D = 38, 44 L kg(-1)) and rapid clearances (CL = 70, 43 mL min(-1) kg(-1)). When given orally, both the pyrazole and the pyrrole leads dose-dependently inhibit stress-induced ACTH release in vivo. ACTH reductions of 84-86% were observed for 30 mg kg(-1) doses.

  DOI：

  10.1021/jm050070m
• 作为产物：
  描述：

  ethyl 3-(1-propylbutylamino)propionate 、 ethyl 6-methyl-2,4-bis(trifluoromethanesulfonyloxy)nicotinate 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 ethyl 4-[(2-ethoxycarbonylethyl)(1-propylbutyl)amino]-6-methyl-2-trifluoromethanesulfonyloxynicotinate
  参考文献：
  名称：

  Potent, Orally Active Corticotropin-Releasing Factor Receptor-1 Antagonists Containing a Tricyclic Pyrrolopyridine or Pyrazolopyridine Core

  摘要：

  Two new classes of tricyclic-based corticotropin-releasing factor (CRF1) receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based molecules 19g and 22a, respectively, were discovered that potently bind the recombinant CRF1 receptor (K-i = 3.5, 2.9 nM) and inhibit adrenocorticotropic hormone (ACTH) release from rat pituitary cell culture (IC50 = 14, 6.8 nM). These compounds show good oral bioavailabity (F = 24%, 7.0%) and serum half-lives in rats (t(1/2) = 6.3, 12 h) and penetrate the rat brain ([brain]/[plasma] = 0.27, 0.52) but tend toward large volumes of distribution (V-D = 38, 44 L kg(-1)) and rapid clearances (CL = 70, 43 mL min(-1) kg(-1)). When given orally, both the pyrazole and the pyrrole leads dose-dependently inhibit stress-induced ACTH release in vivo. ACTH reductions of 84-86% were observed for 30 mg kg(-1) doses.

  DOI：

  10.1021/jm050070m

文献信息

• Chemical compounds
  申请人：——

  公开号：US20040242623A1

  公开（公告）日：2004-12-02

  The present invention relates to tricyclic pyridines compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof: 1

  本发明涉及公式（I）的三环吡啶化合物，包括立体异构体、前药和其药学上可接受的盐或溶剂化物：1
• Tricyclic CRF receptor antagonists
  申请人：SB PHARMCO PUERTO RICO INC. CSC, The United States Corporation Company

  公开号：EP1425281B1

  公开（公告）日：2006-02-01
• US7273871B2
  申请人：——

  公开号：US7273871B2

  公开（公告）日：2007-09-25