MCL-182 | 652133-30-7

• 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: MCL-182
• 英文别名: 3-aminobutorphan；N-cyclobutylmethyl-3-aminomorphinan；(1R,9R,10R)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-amine
• CAS: 652133-30-7
• 化学式: C₂₁H₃₀N₂
• 分子量: 310.483
• InChiKey: HXKMQQLYEGWJQB-CEWLAPEOSA-N

物化性质

• 沸点：
  474.6±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  MCL-182 在 lithium aluminium tetrahydride 、 溴 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 88.0h， 生成 2-(N-methylamino)thiazolo[5,4-b]-N-(cyclobutylmethyl)morphinan dihydrochloride
  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：

  溴甲基环丁烷 在 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 palladium diacetate 、 盐酸羟胺 、 sodium acetate 、 碳酸氢钠 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 MCL-182
  参考文献：
  名称：

  10-酮吗啡喃和3-取代的3-脱氧吗啡喃类似物作为混合的κ和微阿片样物质配体：它们在阿片样物质受体上的结合亲和力的合成和生物学评估。

  摘要：

  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

  DOI：

  10.1021/jm0304156

文献信息

• Synthesis and Preliminary In vitro Investigation of Bivalent Ligands Containing Homo- and Heterodimeric Pharmacophores at μ, δ, and κ Opioid Receptors
  作者：Xuemei Peng、Brian I. Knapp、Jean M. Bidlack、John L. Neumeyer

  DOI：10.1021/jm050577x

  日期：2006.1.1

  A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured in the [S-35]- GTP gamma S binding assay. The data suggest that the stereochemistry of the pharmacophores, the N-substituents of the pharmacophore, ester linkages, and the spacer length were crucial factors for optimum interactions of such ligands at opioid receptor binding sites. These novel ligands as well as their pharmacological properties will serve as the basis for our continuing investigation of such bivalent ligands as probes of the opioid receptor oligomerization phenomena and for in vivo studies as analgesics.
• In-vitro investigation of oxazol and urea analogues of morphinan at opioid receptors
  作者：Xuemei Peng、Brian I. Knapp、Jean M. Bidlack、John L. Neumeyer

  DOI：10.1016/j.bmc.2007.03.076

  日期：2007.6

  A series of 2-amino-oxazole (7 and 8) analogs and 2-one-oxazole analogs (9 and 10) were synthesized from cyclorpban (1) or butorphan (2) and evaluated in-vitro by their binding affinity at mu, delta, and kappa opioid receptors and compared with their 2-aminothiozole analogs 5 and 6. Ligands 7-10 showed decreased affinities at kappa and mu receptors. Urea analogs (11-14) were also prepared from 2-aminocyclorphan (3) or 2-aminobutorphan (4) and evaluated in-vitro by their binding affinity at mu, delta, and kappa opioid receptors. The urea derived opioids retained their affinities at mu receptors while showing increased affinities at 6 receptors and decreased affinities at K receptors. Functional activities of these compounds were measured in the [S-35]GTP(gamma)S binding assay, illustrating that all of these ligands were kappa agonists. At the mu receptor, compounds 11 and 12 were mu agonist/antagonists. (C) 2007 Elsevier Ltd. All rights reserved.
• 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.
• Aminothiazolomorphinans with Mixed κ and μ Opioid Activity
  作者：Tangzhi Zhang、Zhaohua Yan、Anna Sromek、Brian I. Knapp、Thomas Scrimale、Jean M. Bidlack、John L. Neumeyer

  DOI：10.1021/jm101542c

  日期：2011.3.24

  A series of N-substituted and N′-substituted aminothiazole-derived morphinans (5) were synthesized for expanding the structure−activity relationships of aminothiazolo-morphinans. Although their affinities were somewhat lower than their prototype aminothiazolo-N-cyclopropylmorphinan (3), 3-aminothiazole derivatives of cyclorphan (1) containing a primary amino group displayed high affinity and selectivity

  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。