3-trifluoromethyl(sulfonyl)oxy-N-cyclopropylmethylmorphinan | 496848-56-7

• 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: 3-trifluoromethyl(sulfonyl)oxy-N-cyclopropylmethylmorphinan
• 英文别名: (-)-3-trifluoromethanesulfonyloxy-N-cyclopropylmethylmorphinan；N-(1-cyclopropyl)methyl-3-(trifluoromethanesulfonyloxy)morphinan；[(1R,9R,10R)-17-(cyclopropylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] trifluoromethanesulfonate
• CAS: 496848-56-7
• 化学式: C₂₁H₂₆F₃NO₃S
• 分子量: 429.504
• InChiKey: QSDFNMSOLKQEDP-DFQSSKMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-trifluoromethyl(sulfonyl)oxy-N-cyclopropylmethylmorphinan 在 盐酸羟胺 、 sodium acetate 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 36.0h， 生成 MCL 149
  参考文献：
  名称：

  具有混合 κ 和 μ 阿片样物质活性的氨基噻唑吗啡烷

  摘要：

  合成了一系列 N-取代和 N'-取代的氨基噻唑衍生的吗啡喃 ( 5 ) 以扩展氨基噻唑吗啡喃的构效关系。虽然其亲和力一定程度上比其原型aminothiazolo-降低Ñ -cyclopropylmorphinan（3 cyclorphan（的），3-氨基噻唑衍生物1含有伯氨基显示高亲和力和选择性的κ）和μ阿片受体。[ 35 S]GTPγS 结合试验表明，氨基噻唑吗啉是 κ 激动剂，对 μ 阿片受体具有混合激动剂和拮抗剂活性。这些新型 N'-单取代氨基噻唑衍生的吗啡喃可能对药物滥用药物的开发有价值。

  DOI：

  10.1021/jm101542c
• 作为产物：
  描述：

  左啡诺 在 盐酸 、 lithium aluminium tetrahydride 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 为溶剂， 生成 3-trifluoromethyl(sulfonyl)oxy-N-cyclopropylmethylmorphinan
  参考文献：
  名称：

  Preliminary Pharmacological Evaluation of Enantiomeric Morphinans

  摘要：

  A series of levo- and dextromorphinan pairs have been synthesized and evaluated for their affinities to the mu, kappa, and delta opioid receptors, the N-methyl-D-aspartate (NMDA) channel, and sigma 1 and 2 receptors. It was found that levo isomers tended to have higher affinities at the opioid receptors and moderate to high affinities to the NMDA and sigma receptors, while dextro isomers tended to have lower affinities to the opioid receptors but comparatively higher affinities to the NMDA and sigma receptors. This series of compounds have interesting and complex pharmacological profiles, and merit further investigation as potential therapies for drug abuse treatment.

  DOI：

  10.1021/cn400205z

文献信息

• 10-Ketomorphinan and 3-Substituted-3-desoxymorphinan Analogues as Mixed κ and μ Opioid Ligands:  Synthesis and Biological Evaluation of Their Binding Affinity at Opioid Receptors
  作者：Ao Zhang、Wennan Xiong、Jean M. Bidlack、James E. Hilbert、Brian I. Knapp、Mark P. Wentland、John L. Neumeyer

  DOI：10.1021/jm0304156

  日期：2004.1.1

  10-ketomorphinan analogues were synthesized, and their binding affinity at all three opioid receptors was investigated. In most cases, high affinity at micro and kappa receptors, and lower affinity at delta receptor was observed, resulting in good selectivity for micro and kappa receptors. A wide range of substituents can be accommodated on the nitrogen position. The N-(S)-tetrahydrofurfuryl analogue 11 displayed

  合成了一系列10-酮吗啡喃类似物，并研究了它们在所有三个阿片受体上的结合亲和力。在大多数情况下，观察到对micro和kappa受体的亲和力高，而对delta受体的亲和力较低，因此对micro和kappa受体的选择性好。在氮位置上可以容纳各种各样的取代基。N-（S）-四氢糠基类似物11在所有三个受体上显示出最高的亲和力。N-环丁基甲基类似物13对κ受体具有高亲和力和选择性，而N-2-苯基乙基类似物18对微受体具有良好的亲和力和选择性。对3-取代基的进一步修饰表明，一个H键供体是在微受体和κ受体上具有良好亲和力的基本要求。在吗啡烷的3-OH基团上研究了类似的修饰：左啡烷（2a），环烷（2b）和缺少10-酮基的MCL-101（2c）。3-氨基生物立体异构体（40和41）在微受体和kappa受体上表现出相当好的亲和力。吗啡亚系列中的3-甲酰胺基取代（化合物46-48）产生的亲和力与其相应的3-OH
• NEUROPROTECTIVE PROPERTIES OF DEXTROROTATORY MORPHINANS
  申请人：KIM Hyoung-Chun

  公开号：US20050256147A1

  公开（公告）日：2005-11-17

  The present application discloses a pharmaceutical composition for treating Parkinson's disease and psychotropic intoxication/abusive potential, which contains a morphinan compound.

  本申请公开了一种治疗帕金森病和精神药物中毒/滥用潜力的药物组合物，其中包含一种吗啡类化合物。
• Neuroprotective properties of dextrorotatory morphinans
  申请人：——

  公开号：US07691874B2

  公开（公告）日：2010-04-06

  The present application discloses a pharmaceutical composition for treating Parkinson's disease and psychotropic intoxication/abusive potential, which contains a morphinan compound.

  本申请公开了一种用于治疗帕金森病和精神药物中毒/滥用潜力的药物组合物，其中包含一种吗啡样化合物。
• Synthesis, Binding Affinity, and Functional in Vitro Activity of 3-Benzylaminomorphinan and 3-Benzylaminomorphine Ligands at Opioid Receptors
  作者：John L. Neumeyer、Bin Zhang、Tangzhi Zhang、Anna W. Sromek、Brian I. Knapp、Dana J. Cohen、Jean M. Bidlack

  DOI：10.1021/jm3001086

  日期：2012.4.26

  A series of 3-benzylamino-3-desoxymorphinan (I) and 3-benzylamino-3-desoxymorphine (II) derivatives were synthesized and evaluated for their binding affinities, and functional activity data are presented at MOR, KOR, and DOR Some of these ligands were found to have high binding affinity at MOR and KOR and displayed increased selectivity at MOR over KOR and DOR compared to butorphan or cyclorphan. The most selective compound, 3-(3'-hydroxybenzyl)amino-17-methylmorphinan (4g) (24-fold MOR to KOR and 1700-fold MOR to DOR) also showed high binding affinity (0.42 nM to MOR) and was a full agonist in the [S-35]GTP gamma S binding assay. 2-(3'-Hydroxybenzyl)amino-17-cyclopropylmethylmorphinan (17) was found to be a KOR-selective ligand (150-fold over MOR and > 10000-fold over the DORs). Most 3-benzylaminomorphinan derivatives were partial agonists at MOR and full agonists at KOR in the [S-35]GTP gamma S binding assay.
• 2-Aminothiazole-Derived Opioids. Bioisosteric Replacement of Phenols
  作者：Ao Zhang、Wennan Xiong、James E. Hilbert、Emily K. DeVita、Jean M. Bidlack、John L. Neumeyer

  DOI：10.1021/jm049978n

  日期：2004.4.1

  A series of aminothiazole-derived morphinans, benzomorphans, and morphine were synthesized. Although their affinities were somewhat lower than their phenol prototypes, one compound (9a, ATPM) has been identified possessing high affinity and selectivity at the kappa receptor. Functional assays showed that 9a was a full kappa but partial mu agonist; the efficacy at kappa was significantly greater than at mu receptors. This novel compound may be valuable for the development of long-acting analgesics and drug abuse medication.