(-)-3(S),4(S)-dimethyl-4-(3-hydroxyphenyl)piperidine | 119193-27-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (-)-3(S),4(S)-dimethyl-4-(3-hydroxyphenyl)piperidine
• 英文别名: 3-((3S,4S)-3,4-Dimethylpiperidin-4-yl)phenol；3-[(3S,4S)-3,4-dimethylpiperidin-4-yl]phenol
• CAS: 119193-27-0
• 化学式: C₁₃H₁₉NO
• 分子量: 205.3
• InChiKey: HXZDAOSDNCHKFE-MFKMUULPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-3(S),4(S)-dimethyl-4-(3-hydroxyphenyl)piperidine 在 dimethyl sulfide borane 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (R)-7-Hydroxy-3-{(S)-1-[(3S,4S)-4-(3-hydroxy-phenyl)-3,4-dimethyl-piperidin-1-ylmethyl]-2-methyl-propylcarbamoyl}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  （3R）-7-羟基-N-（（1S）-1-[[（（3R，4R）-4-（3-羟基苯基）-3,4-二甲基-1-哌啶基]甲基] -2-的鉴定甲基丙基）-1,2,3,4-四氢-3-异喹啉甲酰胺为新型有效且选择性的阿片类κ受体拮抗剂。

  摘要：

  （3R）-7-羟基-N-（（1S）-1-[[（（3R，4R）-4-（3-羟苯基）-3,4-二甲基-1-哌啶基]甲基] -2-甲基丙基） -1,2,3,4-四氢-3-异喹啉羧酰胺（JDTic）被确定为有效的选择性κ阿片受体拮抗剂。对JDTic类似物的结构活性关系（SAR）研究表明，3,4-二甲基-4-（3-羟基苯基）哌啶核心结构的3R，4R立体化学，7-羟基-1,2的3R附着， 3,4-四氢异喹啉基团和2-甲基丙基（异丙基）基团的1S构型均对其Kappa效能和选择性很重要。结果表明，与其他kappa阿片类拮抗剂（例如nor-BNI和GNTI）一样，JDTic在[（35）S] GTPgammaS功能测定中需要第二个碱性氨基来表达有效和选择性的kappa拮抗剂活性。然而，与先前报道的Kappa拮抗剂不同，JDTic还需要第二酚基团，该第二酚基团必须紧靠该第二碱性氨基。可以使用“消息地址”概念合理

  DOI：

  10.1021/jm030094y
• 作为产物：
  描述：

  3-溴苯基异丙醚 在 sodium tetrahydroborate 、 正丁基锂 、 D-(+)-二对甲基苯甲酰酒石酸 、 氢溴酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 溶剂黄146 、 乙酸乙酯 、 萘烷 为溶剂， 反应 25.0h， 生成 (-)-3(S),4(S)-dimethyl-4-(3-hydroxyphenyl)piperidine
  参考文献：
  名称：

  Alvimopan所有可能的非对映异构体的合成与表征

  摘要：

  发现许多生物物质和天然产物以对映体对形式存在。在这种情况下，如图1所示的alvimopan 1具有三个手性中心，因此理论上将具有8个非对映异构体。在这些化合物中，发现一种非对映异构体可作为阿片样物质拮抗剂发挥作用，并被指定用于术后肠梗阻的治疗。为了确定不需要的非对映异构体的百分比含量并定义迄今为止从未有过的原料药的规格，因此，我们尝试合成和表征所有可能的非对映异构体。在这里，我们介绍了我们的策略，由于在3个和4个手性碳原子中心处存在反相关关系，该策略已成功执行，从而获得了四种实际可行的非对映异构体。有趣的是，

  DOI：

  10.13005/ojc/340246

文献信息

• Piperidine derivatives
  申请人：ELI LILLY AND COMPANY

  公开号：EP0506478A1

  公开（公告）日：1992-09-30

  3,4,4-trisubstitutedpiperidinyl-alkyl-carboxylates and intermediates for their preparation are provided. These piperidine-N-alkylcarboxylates are useful as peripheral opioid antagonists.

  提供了 3,4,4-三取代哌啶-N-烷基羧酸盐及其制备中间体。这些哌啶-N-烷基羧酸盐可用作外周阿片拮抗剂。
• Structure-activity relationships of trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine antagonists for .mu.- and .kappa.-opioid receptors
  作者：Dennis M. Zimmerman、J. David Leander、Buddy E. Cantrell、Jon K. Reel、John Snoddy、Laurane G. Mendelsohn、Bryan G. Johnson、Charles H. Mitch

  DOI：10.1021/jm00072a001

  日期：1993.10

  A series of racemic N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines were evaluated for opioid agonist and antagonist activity at mu and kappa receptors. Several highly potent mu and kappa antagonists were discovered; however, no compounds with high selectivity for either the mu or kappa receptor were identified. Importantly, no derivative was found to have significant opioid agonist activity. Two derivatives were resolved, and the activities of the enantiomers were investigated. Only a limited stereochemical effect on opioid receptor selectivities was observed. The structure-activity relationships described establish the existence of an important lipophilic binding site distal to the nitrogen for both mu and kappa receptors and confirm the pure opioid antagonist pharmacophore nature of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine structure.
• 3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines: opioid antagonists with potent anorectant activity
  作者：Charles H. Mitch、J. David Leander、Laurane G. Mendelsohn、Walter N. Shaw、David T. Wong、Buddy E. Cantrell、Bryan G. Johnson、John K. Reel、John D. Snoddy

  DOI：10.1021/jm00072a002

  日期：1993.10

  A series of (3R*,4R*)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists with varying substituents on the nitrogen were evaluated for their effect on food consumption in obese Zucker rats. Opioid affinity (mu, kappa, and delta for selected compounds) and opioid antagonist activity (mu and kappa) were characterized and compared to effects on food consumption. No compounds with high selectivity for either mu or kappa receptors were discovered. However, compounds in the series had exceptional potency as opioid antagonists and in reducing food consumption in the obese Zucker rat. In contrast, a few compounds with high potency as opioid antagonists had much weaker potency for inhibiting food consumption. (3R,4R)-3,4-Dimethyl-1-[(3S)-3-hydroxy-3-cyclohexyl-propyl]-4-(3-hydroxyphenyl)piperidine(11,LY255582)emerged as having the best activity profile, both in reducing food consumption and as an opioid antagonist. Compound 11 is a highly potent mu, kappa-, and delta-opioid antagonist with possible clinical utility as an appetite suppressant for weight loss.
• Discovery of a Potent, Peripherally Selective trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonist for the Treatment of Gastrointestinal Motility Disorders
  作者：Dennis M. Zimmerman、Jaswant S. Gidda、Buddy E. Cantrell、Darryle D. Schoepp、Bryan G. Johnson、J. David Leander

  DOI：10.1021/jm00041a003

  日期：1994.7

  Structure-activity relationship studies were pursued within N-substituted-trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (K-i = 0.77, 40, and 4.4 nM for mu, kappa, and delta receptors, respectively). It is a potent mu receptor antagonist following parenteral and oral administration and distributes selectively (>200-fold selectivity) to peripheral receptors. Thus, 3 has properties suitable for the clinical investigation of mu opioid receptor involvement in GI motility disorders.
• US5250542A
  申请人：——

  公开号：US5250542A

  公开（公告）日：1993-10-05