17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7β-carbonitrile | 742104-54-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7β-carbonitrile
• 英文别名: (1R,2S,6R,14R,15R,16S)-5-(cyclopropylmethyl)-11,15-dimethoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,18-tetraene-16-carbonitrile
• CAS: 742104-54-7
• 化学式: C₂₅H₂₈N₂O₃
• 分子量: 404.509
• InChiKey: PVPRBVPNRDDQCI-GISBNZKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  54.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7β-carbonitrile 在 硫酸 、 三溴化硼 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dihydroxy-6,14-endoethenomorphinan-7α-(N-t-butyl)carboxamide
  参考文献：
  名称：

  Drug design and synthesis of ε opioid receptor agonist: 17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dihydroxy-6,14-endoethenomorphinan-7α-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative ε opioid receptor

  摘要：

  Here we report the new drug design and synthesis of a series of 6,14-endoethenomorphinan-7-carboxamide derivatives as a putative E: opioid receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821), showed agonistic activity for a putative E opioid receptor (IC50 = 71.71 nM) in the rat vas deferens (RVD) preparations. TAN-821 stimulated the binding of the nonhydrolyzable guanosine 5'-triphosphate analog, guanosine 5'-(gamma-thio)-triphosphate (GTPgammaS), to the mouse pons/medulla membrane via the activation of putative E: opioid receptor. Moreover, TAN-821 given intracerbroventricularly (i.c.v.) produced a marked antinociception in the tail-flick test (ED50 = 1.73 mug) and the hot-plate test (ED50 = 2.05 mug) in a dose-dependent manner. The antinociception induced by TAN-821 administered i.c.v. was blocked by the i.c.v.-pretreatment with a putative epsilon opioid receptor partial agonist beta-endorphin [1-27], but not a mu opioid receptor antagonist beta-FNA, a delta opioid receptor antagonist NTI, or a kappa opioid receptor antagonist nor-BNI. The present results suggest that TAN-821 may be a useful tool for the investigation on the pharmacological properties of the putative epsilon opioid receptor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.05.024
• 作为产物：
  描述：

  N-(cyclopropylmethyl)northebaine 、 丙烯腈 以 甲苯 为溶剂， 以37%的产率得到17-(cyclopropylmethyl)-4,5α-epoxy-3,6β-dimethoxy-6,14-endoethenomorphinan-7α-carbonitrile
  参考文献：
  名称：

  [EN] BUPRENORPHINE ANALOGS AS OPIOD RECEPTOR MODULATORS
  [FR] ANALOGUES DE BUPRÉNORPHINE EN TANT QUE MODULATEURS D'UN RÉCEPTEUR DES OPIOÏDES

  摘要：

  本发明涉及公式I、公式II、公式III、公式IV和公式V的哌替啶类似化合物，其中R1、R2、R3a、R3b、R、15a、R15b、X、Q、G和Y如本文所定义。本发明的化合物可用于治疗疼痛和其他受阿片类受体活性调节的疾病。

  公开号：

  WO2014087226A1

文献信息

• [EN] 7-BETA ANALOGS OF ORVINOLS<br/>[FR] ANALOGUES 7-BÊTA D'ORVINOLS
  申请人：PURDUE PHARMA LP

  公开号：WO2015100092A3

  公开（公告）日：2015-10-29
• BUPRENORPHINE ANALOGS
  申请人：Purdue Pharma L.P.

  公开号：US20140163058A1

  公开（公告）日：2014-06-12

  The present invention is directed to Buprenorphine Analog compounds of the Formula I, Formula II, Formula III, Formula IV, and Formula V, wherein R 1 , R 2 , R 3a , R 3b , R 15a , R 15b , X, Q, G, and Y are as defined herein. Compounds of the Invention are useful for treating pain and other conditions modulated by activity of opioid receptors.
• 7-BETA ANALOGS OF ORVINOLS
  申请人：PURDUE PHARMA L.P.

  公开号：US20160333020A1

  公开（公告）日：2016-11-17

  The application is directed to compounds of Formula I (I) and pharmaceutically acceptable salts and solvates thereof, wherein R 1 , R 1a , R 1b , X, Y, Z, G, Q, W 1 and W 2 are defined as set forth in the specification. The invention is also directed to use of the compounds of Formula I and the pharmaceutically acceptable salts and solvates thereof to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. Certain compounds of the present invention are especially useful for treating pain.
• US9175000B2
  申请人：——

  公开号：US9175000B2

  公开（公告）日：2015-11-03