N-cyclopropylmethylnorcodeine | 77794-51-5

• 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: N-cyclopropylmethylnorcodeine
• 英文别名: 17-(cyclopropylmethyl)-7,8-didehydro-4,5α-epoxy-3-methoxymorphinan-6α-ol；N-Cyclopropylmethyl-norcodein；17-cyclopropylmethyl-4,5α-epoxy-3-methoxy-morphin-7-en-6α-ol；(4R,4aR,7S,7aR,12bS)-3-(cyclopropylmethyl)-9-methoxy-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
• CAS: 77794-51-5
• 化学式: C₂₁H₂₅NO₃
• 分子量: 339.434
• InChiKey: ALYLJTGVQCWITR-OBRACTJBSA-N

物化性质

• 沸点：
  506.5±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-cyclopropylmethylnorcodeine 在 吡啶盐酸盐 作用下， 生成 N-(环丙基甲基)去甲吗啡
  参考文献：
  名称：

  某些具有强镇痛活性的强效吗啡拮抗剂。

  摘要：

  DOI：

  10.1021/jm00332a002
• 作为产物：
  描述：

  去甲可待因 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 28.0h， 生成 N-cyclopropylmethylnorcodeine
  参考文献：
  名称：

  某些具有强镇痛活性的强效吗啡拮抗剂。

  摘要：

  DOI：

  10.1021/jm00332a002

文献信息

• Application of the Mitsunobu Reaction for Morphine Compounds. Preparation of 6β-Aminomorphine and Codeine Derivatives
  作者：Csaba Simon、Sandor Hosztafi、Sándor Makleit

  DOI：10.1080/00397919208020855

  日期：1992.3

  Abstract By the application of the Mitsunobu reaction several new 7 8 6β-aminomorphine and codeine derivatives, carrying a Δ7,8 double bond in ring C have been synthesized. The catalytic hydrogenation of these compounds offered a new stereoselective way for the synthesis of the corresponding 6β-amino-dihydro analogues. The different conformation of ring C of the saturated and unsaturated amino compounds

  摘要 通过Mitsunobu反应合成了几种新的7 8 6β-氨基吗啡和可待因衍生物，在C环上带有一个Δ7,8双键。这些化合物的催化氢化为合成相应的 6β-氨基-二氢类似物提供了一种新的立体选择性方法。饱和和不饱和氨基化合物的环 C 的不同构象允许研究构效关系，并且通过不饱和衍生物的氚化可以检查底物 - 受体相互作用。
• 6 .beta.-Thiomorphine derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US05219861A1

  公开（公告）日：1993-06-15

  A novel morphine derivative represented by the following general formula: ##STR1## wherein R.sub.1 represents a hydrogen atom, a lower alkyl group or a lower alkanoyl group; R.sub.2 represents a hydrogen atom, a lower alkylthio group, an aryl group, a lower alkoxycarbonylalkyl group, a lower alkyl group or a lower alkanoyl group; R.sub.3 represents a lower cycloalkylmethyl group or an allyl group, and a pharmaceutically acceptable acid addition salt thereof. The compound of the above general formula shows an analgesic activity 5 or more times as high as that of morphine and a narcotic antagonist action. Further, it exhibits an extremely low drug dependence. These properties make it highly useful as an active ingredient of drugs such as analgesics or anesthetics.

  一种新的吗啡衍生物，其通式如下：##STR1## 其中，R.sub.1代表氢原子、低碳基或低脂肪酰基；R.sub.2代表氢原子、低烷基硫基、芳基、低烷氧羰基烷基、低烷基或低脂肪酰基；R.sub.3代表低环烷基甲基或烯丙基，并且其药学上可接受的酸盐也包括在内。以上通式的化合物显示出比吗啡高5倍以上的镇痛活性和镇痛拮抗剂作用。此外，它表现出极低的药物依赖性。这些特性使其成为镇痛剂或麻醉剂等药物的活性成分非常有用。
• δ Opioid Affinity and Selectivity of 4-Hydroxy-3-methoxyindolomorphinan Analogues Related to Naltrindole
  作者：Andrew Coop、Richard B. Rothman、Christina Dersch、John Partilla、Frank Porreca、Peg Davis、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1021/jm9807003

  日期：1999.5.1

  To investigate the effect of the introduction of a 4-phenolic substituent on the delta opioid affinity and selectivity of the indolomorphinans, a range of 4-phenolic analogues of naltrindole were prepared and evaluated in in vitro assays. Although the majority of the ligands displayed poor affinity for all three opioid receptors (mu, kappa, delta), 17-cyclopropylmethyl-6,7-didehydro-4-hydroxy-3-methoxy-6,7:2',3'-indolomorphinan (13) was an exception, displaying excellent delta binding selectivity (delta K-i = 7 nM, mu/delta = 1900, mu/kappa = 1130). GTP-gamma-S functional assays showed 13 to be a selective delta antagonist, albeit with lower potency than naltrindole. Although the reason for the unique profile of 13 could not be determined, these results validate our approach of introducing groups into the indolomorphinans that are known to reduce mu activity, to obtain increased delta selectivity.
• Analgesic narcotic antagonists. 6. 7.beta.,8.beta.-Methano- and 7.beta.,8.beta.-epoxydihydrocodeinone
  作者：Michael P. Kotick

  DOI：10.1021/jm00138a016

  日期：1981.6

  Reaction of codeinone (2) with CH2N2 in the presence of Pd(OAc)2 yielded mixtures of starting material and (2) and 7 beta, 8 beta-methanodihydrocodeinone (3). Initial resolution of this mixture was achieved via carbonyl reduction followed by chromatography to give pure 7 beta, 8 beta-methanodihydrocodeine (4), which was oxidized to 3. Reaction of the mixture containing 2 and 3 with mercaptoethanol and NaOH [2 leads to 8 beta-[(hydroxyethyl)thio]dihydrocodeinone (5)] allowed selective crystallization of 3. The beta configuration of the cyclopropane ring in 3 was established by cleavage with aqueous HCl to give the 8 beta-(chloromethyl) compound 6, followed by carbonyl reduction and dehalogenation to 8 beta-methyldihydrocodeine (8). Reaction of the N-(cycloalkylmethyl) derivatives (13 and 18) of 2 with CH2N2/Pd(OA)2 gave potential mixed agonist-antagonists and 14 and 19, which were purified by reduction-oxidation (14) or mercaptoethanol-base treatment (19). Compound 2, on oxidation with alkaline peroxide, gave the previously reported 7 beta, 8 beta-epoxydihydrocodeinone (22) as the hemimethanol ketal (21). Compound 3 was about ninefold more potent an agonist than dihydrocodeine, and the N-(cyclopropylmethyl)-7 beta, 8 beta-methano compound 19 had moderately potent mixed agonist-narcotic antagonist properties.
• US5219861A
  申请人：——

  公开号：US5219861A

  公开（公告）日：1993-06-15