17-cyclopropylmethyl-8,14-dehydro-3-methoxymorphinan-6-spiro-2'-(1',3'-dioxolane) | 1069111-48-3

• 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: 17-cyclopropylmethyl-8,14-dehydro-3-methoxymorphinan-6-spiro-2'-(1',3'-dioxolane)
• 英文别名: (1'R,9'R)-17'-(cyclopropylmethyl)-4'-methoxyspiro[1,3-dioxolane-2,13'-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,10-tetraene]
• CAS: 1069111-48-3
• 化学式: C₂₃H₂₉NO₃
• 分子量: 367.488
• InChiKey: FSPULMGWLYQWNS-YADHBBJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  17-cyclopropylmethyl-8,14-dehydro-3-methoxymorphinan-6-spiro-2'-(1',3'-dioxolane) 在 sodium tetrahydroborate 、 氯化亚砜 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 34.83h， 生成 methyl 2-[(1S,9R,13R)-10-(cyclopropylmethyl)-13-(hydroxymethyl)-4-methoxy-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-1-yl]acetate
  参考文献：
  名称：

  BENZOMORPHAN ANALOGS AND THE USE THEREOF

  摘要：

  本发明涉及如下所示的Formula I-ID的苯吗啉类似化合物，其中R1、R2a、R2b、R3和R4的定义如本文所述。本发明的化合物可用于治疗疼痛、便秘以及其他受阿片类和ORL-1受体活性调节的疾病。

  公开号：

  US20140221419A1
• 作为产物：
  描述：

  纳曲酮EP杂质J 在 吡啶 、 氯化亚砜 、 1,3-双(二苯基膦)丙烷 、 palladium diacetate 、 氯化铵 、 caesium carbonate 、 对甲苯磺酸 、 锌 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 55.83h， 生成 17-cyclopropylmethyl-8,14-dehydro-3-methoxymorphinan-6-spiro-2'-(1',3'-dioxolane)
  参考文献：
  名称：

  7,8-Cyclicmorphinan Analogs

  摘要：

  本申请涉及式I-A的化合物以及药用可接受的盐和溶剂化物，其中Cy、R1a-R3a、R4a和R4b的定义如说明书所述。本发明还涉及将式I-A的化合物用于治疗对一或多个阿片受体调节有反应的疾病，或作为合成中间体。本发明中的某些化合物特别适用于治疗疼痛。

  公开号：

  US20140187571A1

文献信息

• Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists
  作者：Yoshihiro Ida、Toru Nemoto、Shigeto Hirayama、Hideaki Fujii、Yumiko Osa、Masayuki Imai、Takashi Nakamura、Toshiyuki Kanemasa、Akira Kato、Hiroshi Nagase

  DOI：10.1016/j.bmc.2011.11.047

  日期：2012.1

  The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the delta opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the 8 receptor over the mu receptor than the corresponding SN-28 derivatives with the 3-hydroxy group (SN-11, 23, 28). Derivatives with the 4-hydroxy group showed potent agonist activities for the 5 receptor in the [S-35]GTPyS binding assay. Although the 17-cyclopropylmethyl derivative (SN-11) with a 3-hydroxy group showed the lowest selectivity for the delta receptor among the morphinan derivatives, the agonist activity toward the delta receptor was the most potent for candidates with the 3-hydroxy group. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis of a Stable Iminium Salt and Propellane Derivatives
  作者：Hiroshi Nagase、Naoshi Yamamoto、Toru Nemoto、Kenji Yoza、Kenshu Kamiya、Shuichi Hirono、Shinobu Momen、Naoki Izumimoto、Ko Hasebe、Hidenori Mochizuki、Hideaki Fujii

  DOI：10.1021/jo801276z

  日期：2008.10.17

  The treatment of morphinan I with NaH and MsCl provided very stable iminium salt 7 possessing propellane skeleton. One of the synthesized iminium salts 7, isobutyl derivative 7b, was crystallized and its structure was determined by X-ray crystallography. The natural bond orbital analysis suggested that the stability of the iminium should result from the stereoelectronic effect (hyperconjugation) attributed to their own structures.
• Design and synthesis of novel delta opioid receptor agonists and their pharmacologies
  作者：Hiroshi Nagase、Yumiko Osa、Toru Nemoto、Hideaki Fujii、Masayuki Imai、Takashi Nakamura、Toshiyuki Kanemasa、Akira Kato、Hiroaki Gouda、Shuichi Hirono

  DOI：10.1016/j.bmcl.2009.03.099

  日期：2009.5

  We re-examined the accessory site of the 4,5-epoxymorphinan skeleton by CAMDAS conformational analysis in an effort to deign novel delta opioid receptor antagonists. We synthesized three novel compounds (SN-11, 23 and 28) with a 10-methylene bridge and without a 4,5-epoxy ring. Among them, compounds SN-23 (17-isobutyl derivative) and SN-28 (17-methyl derivative) showed very strong agonist activity (over 10 times more than TAN-67). SN-28 also showed high delta selectivity. The delta agonist activity of SN-23 was weaker than that of SN-28, but in terms of the delta selectivity, SN-23 was higher than that of SN-28. These unexpected results indicated that the 4,5-epoxy ring, but not the 10-methylene bridge, was an accessory site in delta opioid receptor agonists. (C) 2009 Elsevier Ltd. All rights reserved.
• 7,8-CYCLICMORPHINAN ANALOGS
  申请人：Purdue Pharma LP

  公开号：EP2941430B1

  公开（公告）日：2017-04-26
• US8957084B2
  申请人：——

  公开号：US8957084B2

  公开（公告）日：2015-02-17