3-(3-(2-cyano-4-fluorophenyl)-1,2,4-oxadiazol-5-yl)propionic acid | 1051372-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-(2-cyano-4-fluorophenyl)-1,2,4-oxadiazol-5-yl)propionic acid
• 英文别名: 3-[3-(2-cyano-4-fluorophenyl)-1,2,4-oxadiazol-5-yl]propanoic acid
• CAS: 1051372-01-0
• 化学式: C₁₂H₈FN₃O₃
• 分子量: 261.212
• InChiKey: DXCBYFPDEHSSAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.76
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  100.01
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-(3-(2-cyano-4-fluorophenyl)-1,2,4-oxadiazol-5-yl)propionic acid 、 2-(3-amino-9H-carbazol-9-yl)ethan-1-ol hydrochloride 在 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 diethylaminodifluorosulfinium tetrafluoroborate 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 3-[3-(2-cyano-4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-N-[9-(2-fluoroethyl)-9H-carbazol-3-yl]propanamide
  参考文献：
  名称：

  Development of fluorinated CB2 receptor agonists for PET studies

  摘要：

  A convergent strategy was followed to modify systematically carbazole based CB2 receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and Y in 7) were varied systematically. The highest CB2 affinity was found for the 2-fluoroethyl substituted carbazole derivative 20a (K-i = 5.8 nM) containing the propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies 20a fits nicely into the binding pocket of the CB2 receptor, but elongation of the fluoroethyl side chain leads to a different binding mode of the ligands. The high CB2 affinity together with the high selectivity over the CB2 subtype qualifies the fluoroethyl derivative 20a to be developed as a PET tracer. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.040
• 作为产物：
  描述：

  3-[3-(2-溴-4-氟苯基)-1,2,4-恶二唑-5-基]-丙酸 在 硫酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 20.25h， 生成 3-(3-(2-cyano-4-fluorophenyl)-1,2,4-oxadiazol-5-yl)propionic acid
  参考文献：
  名称：

  Development of fluorinated CB2 receptor agonists for PET studies

  摘要：

  A convergent strategy was followed to modify systematically carbazole based CB2 receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and Y in 7) were varied systematically. The highest CB2 affinity was found for the 2-fluoroethyl substituted carbazole derivative 20a (K-i = 5.8 nM) containing the propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies 20a fits nicely into the binding pocket of the CB2 receptor, but elongation of the fluoroethyl side chain leads to a different binding mode of the ligands. The high CB2 affinity together with the high selectivity over the CB2 subtype qualifies the fluoroethyl derivative 20a to be developed as a PET tracer. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.040

文献信息

• Discovery and Optimization of a Novel Series of <i>N</i>-Arylamide Oxadiazoles as Potent, Highly Selective and Orally Bioavailable Cannabinoid Receptor 2 (CB₂) Agonists
  作者：Yuan Cheng、Brian K. Albrecht、James Brown、John L. Buchanan、William H. Buckner、Erin F. DiMauro、Renee Emkey、Robert T. Fremeau、Jean-Christophe Harmange、Beth J. Hoffman、Liyue Huang、Ming Huang、Josie Han Lee、Fen-Fen Lin、Matthew W. Martin、Hung Q. Nguyen、Vinod F. Patel、Susan A. Tomlinson、Ryan D. White、Xiaoyang Xia、Stephen A. Hitchcock

  DOI：10.1021/jm800463f

  日期：2008.8.1

  describe the discovery of a novel class of oxadiazole derivatives from which potent and selective CB2 agonist leads were developed. Initial hit 7 was identified from a cannabinoid target-biased library generated by virtual screening of sample collections using a pharmacophore model in combination with a series of physicochemical filters. 7 was demonstrated to be a selective CB2 agonist (CB2 EC50 = 93

  CB2受体是止痛药和抗炎药的有吸引力的治疗靶标。在本文中，我们描述了发现一类新的恶二唑衍生物的发现，由此开发了有效的和选择性的CB2激动剂。通过使用药效团模型结合一系列物理化学过滤器对样品集合进行虚拟筛选，从大麻靶偏倚的文库中识别出最初的第7个匹配项。7被证明是选择性CB2激动剂（CB2 EC50 = 93 nM，Emax = 98％，CB1 EC50> 10 microM）。但是，该化合物在大鼠中表现出较差的溶解性和相对较高的清除率，导致口服生物利用度低。在本文中，我们报告了有关提高功效，理化性质和溶解度的7条途径的详细SAR研究。