3-(5-(3-(pyridin-2-ylamino)propoxy)-1H-indol-1-yl)propanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(5-(3-(pyridin-2-ylamino)propoxy)-1H-indol-1-yl)propanoic acid
• 英文别名: 3-{5-[3-(Pyridin-2-ylamino)-propoxy]-indol-1-yl}-propionic acid；3-[5-[3-(pyridin-2-ylamino)propoxy]indol-1-yl]propanoic acid
• 化学式: C₁₉H₂₁N₃O₃
• 分子量: 339.394
• InChiKey: AJDOOWNOWOSWPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-苄氧基吲哚 在 palladium on activated charcoal sodium hydroxide 、 三丁基膦 、 氢气 、 sodium hydride 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(5-(3-(pyridin-2-ylamino)propoxy)-1H-indol-1-yl)propanoic acid
  参考文献：
  名称：

  Non-peptidic αvβ3 antagonists containing indol-1-yl propionic acids

  摘要：

  We describe the synthesis and structure/activity relationship of RGD mimetics that are potent inhibitors of the integrin alpha(v)beta(3)- Indol-1-yl propionic acids containing a variety of basic moieties at the 5-position, as well as substitutions alpha and beta to the carboxy terminus were synthesized and evaluated. Novel compounds with improved potency have been identified. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.028

文献信息

• Design, Synthesis, and Biological Evaluation of Novel Potent and Selective α_vβ₃/α_vβ₅ Integrin Dual Inhibitors with Improved Bioavailability. Selection of the Molecular Core
  作者：Juan José Marugán、Carl Manthey、Beth Anaclerio、Lou Lafrance、Tianbao Lu、Tom Markotan、Kristi A. Leonard、Carl Crysler、Stephen Eisennagel、Malini Dasgupta、Bruce Tomczuk

  DOI：10.1021/jm049725u

  日期：2005.2.1

  A novel series of potent and selective alpha(v)beta(3)/alpha(v)beta(5) dual inhibitors was designed, synthesized, and evaluated against several integrins. These compounds were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhaced rigidity (i.e., (2-pyridylamino)propoxy versus the 2-(6-methylamino-2-pyridyl)ethoxy) led to improved activity toward alpha(v)beta(3). Exemplary oral bioavailability in mice was achieved using the indole central scaffold. Although, oral bioavailability was maintained when the indole molecular core was replace with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity. However, the indole series displayed the best in vivo pharmacokinetic properties. Thus, the indole series was selected for further structure-activity relationships to obtain more potent alpha(v)beta(3)/alpha(v)beta(5) dual antagonist with improved oral bioavailability.
• SUBSTITUTED INDOLES AND THEIR USE AS INTEGRIN ANTAGONISTS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1425010B1

  公开（公告）日：2011-10-26
• Non-peptidic αvβ3 antagonists containing indol-1-yl propionic acids
  作者：Kristi Leonard、Wenxi Pan、Beth Anaclerio、Joan M. Gushue、Zihong Guo、Renee L. DesJarlais、Marge A. Chaikin、Jennifer Lattanze、Carl Crysler、Carl L. Manthey、Bruce E. Tomczuk、Juan Jose Marugan

  DOI：10.1016/j.bmcl.2005.01.028

  日期：2005.5

  We describe the synthesis and structure/activity relationship of RGD mimetics that are potent inhibitors of the integrin alpha(v)beta(3)- Indol-1-yl propionic acids containing a variety of basic moieties at the 5-position, as well as substitutions alpha and beta to the carboxy terminus were synthesized and evaluated. Novel compounds with improved potency have been identified. (c) 2005 Elsevier Ltd. All rights reserved.