(1S,5R,13R,14R,17S)-4-(cyclopropylmethyl)-14,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7,9,11(18)-triene-10-carboxamide | 1122596-70-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (1S,5R,13R,14R,17S)-4-(cyclopropylmethyl)-14,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7,9,11(18)-triene-10-carboxamide
• 英文别名: (4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carboxamide
• CAS: 1122596-70-6
• 化学式: C₂₁H₂₆N₂O₄
• 分子量: 370.448
• InChiKey: YQOPEESTHCLTGK-JBJCYXPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  96
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carbonitrile 在 氢氧化钾 、 水 作用下， 以 叔丁醇 为溶剂， 生成 (1S,5R,13R,14R,17S)-4-(cyclopropylmethyl)-14,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7,9,11(18)-triene-10-carboxamide
  参考文献：
  名称：

  Syntheses and opioid receptor binding properties of carboxamido-substituted opioids

  摘要：

  A series of 15 novel opioid derivatives were made where the prototypic phenolic-OH group of traditional opioids was replaced by a carboxamido (CONH2) group. For 2,6-methano-3-benzazocines and morphinans similar or, in a few instances, enhanced affinity for mu, delta and kappa opioid receptors was observed when the OH --> CONH2 switch was applied. For 4,5 alpha-epoxymorphinans, binding affinities for the corresponding carboxamide derivatives were much lower than the OH partner consistent with our pharmacophore hypothesis concerning carboxamide bioactive conformation. The active metabolite of tramadol and its carboxamide counterpart had comparable affinities for the three receptors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.134

文献信息

• SAMIDORPHAN (ALKS 33) IN COMBINATION WITH BUPRENORPHINE FOR THE TREATMENT OF DEPRESSIVE DISORDERS
  申请人：Alkermes Pharma Ireland Limited

  公开号：EP3153171A1

  公开（公告）日：2017-04-12

  The invention relates to a composition comprising buprenorphine and a µ opioid receptor antagonist, wherein the composition is characterized by an Agonist Antagonist Activity Index (AAnAI) of between about 0.7 and about 2.2; wherein; AAnAI=/EC50cmaxBUPcmaxANTAGONIST/IC50.

  本发明涉及一种包含丁丙诺啡和μ阿片受体拮抗剂的组合物，其中该组合物的特征在于激动剂拮抗剂活性指数（AAnAI）在约0.7和约2.2之间；其中；AAnAI=/EC50cmaxBUPcmaxANTAGONIST/IC50。
• MORPHINAN DERIVATIVES WITH HIGH ORAL BIOAVAILABILITY
  申请人：Alkermes Pharma Ireland Limited

  公开号：EP3170395A1

  公开（公告）日：2017-05-24

  The instant application relates to morphinan derivatives of formula I with enhanced oral bioavailability for the treatment of diseases associated with opioid receptor activity or blockade including alcohol and opiate addiction.

  本申请涉及式 I 吗啡烷衍生物，该衍生物具有更高的口服生物利用度，可用于治疗与阿片受体活性或阻断有关的疾病，包括酒精成瘾和阿片成瘾。
• MORPHINAN DERIVATIVES FOR THE TREATMENT OF DRUG OVERDOSE
  申请人：Alkermes Pharma Ireland Limited

  公开号：EP3569234A1

  公开（公告）日：2019-11-20

  The instant application relates to morphinan derivatives of Formula I with sustained effectiveness in treating drug toxicity and overdose:

  本申请涉及在治疗药物毒性和药物过量方面具有持续疗效的式 I 吗啡烷衍生物：
• Compositions of buprenorphine and μ antagonists
  申请人：Alkermes Pharma Ireland Limited

  公开号：US10314838B2

  公开（公告）日：2019-06-11

  The invention relates to a composition comprising buprenorphine and a μ opioid receptor antagonist, wherein the composition is characterized by an Agonist Antagonist Activity Index (AAnAI) of between about 0.7 and about 2.2; wherein; AAnAI = [ c ma ⁢ ⁢ x ⁡ ( BUP ) / EC 50 ] [ c ma ⁢ ⁢ x ⁡ ( ANTAGONIST ) / IC 50 ] .

  本发明涉及一种由丁丙诺啡和μ阿片受体拮抗剂组成的组合物，其中该组合物的特征在于其激动剂拮抗剂活性指数（AAnAI）在约0.7和约2.2之间；其中； AAnAI = [ c ma x ( BUP ) / 欧共体 50 ] [ c ma x ( 副标题 ) / 集成电路 50 ] .
• COMPOSITIONS OF BUPRENORPHINE AND MU-OPIOID RECEPTOR ANTAGONISTS
  申请人：Alkermes Pharma Ireland Limited

  公开号：EP2790702B1

  公开（公告）日：2020-04-01