biphenyl-3-yl cyclohexylcarbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: biphenyl-3-yl cyclohexylcarbamate
• 英文别名: URB524；cyclohexylcarbamic acid biphenyl-3-yl ester；biphenyl-N-cyclopentyl-carbamate；(3-phenylphenyl) N-cyclohexylcarbamate
• 化学式: C₁₉H₂₁NO₂
• 分子量: 295.381
• InChiKey: KGKDDSYRBQOMLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  苯硼酸 在 N-甲基吡咯烷酮 、 6,6'-二甲基-2,2'-联吡啶 、 tetrakis(acetonitrile)palladium(II) tetrafluoroborate 、 氧气 、 三乙胺 、 三氟乙酸 作用下， 以 二甲基亚砜 为溶剂， 70.0~120.0 ℃ 、506.66 kPa 条件下， 生成 biphenyl-3-yl cyclohexylcarbamate
  参考文献：
  名称：

  间取代苯酚衍生物的连续流合成

  摘要：

  开发了两种互补的微反应器技术，用于研究气液两相反应和间位反应的制备取代的苯酚衍生物。第一个毛细管微反应器由T型接头和简单的毛细管组成，可实现微克级的氧化Heck /脱氢反应，并缩短了反应时间。氧化性Heck /脱氢反应的总顺序时间从传统的批处理系统中的2160分钟优化到微化学系统中的130分钟。第二个管内微反应器由可透气的内管和不可透气的外管组成，在由第一个微克规模的研究确定的最佳安全性和经济性条件下，成功地进行了克级合成。这两种微反应器在探索涉及气态和液态试剂的反应方面具有巨大潜力。

  DOI：

  10.1021/acs.oprd.5b00077

文献信息

• Design, Synthesis, and Structure−Activity Relationships of Alkylcarbamic Acid Aryl Esters, a New Class of Fatty Acid Amide Hydrolase Inhibitors
  作者：Giorgio Tarzia、Andrea Duranti、Andrea Tontini、Giovanni Piersanti、Marco Mor、Silvia Rivara、Pier Vincenzo Plazzi、Chris Park、Satish Kathuria、Daniele Piomelli

  DOI：10.1021/jm021119g

  日期：2003.6.1

  Fatty acid amide hydrolase (FAAH), an intracellular serine hydrolase enzyme, participates in the deactivation of fatty acid ethanolamides such as the endogenous cannabinoid anandamide, the intestinal satiety factor oleoylethanolamide, and the peripheral analgesic and anti-inflammatory factor palmitoylethanolamide. In the present study, we report on the design, synthesis, and structure-activity relationships

  脂肪酸酰胺水解酶（FAAH）是一种细胞内丝氨酸水解酶，参与脂肪酸乙醇酰胺的失活，例如内源性大麻素大麻素，肠饱足性因子油酰基乙醇酰胺以及外周镇痛和抗炎因子棕榈酰乙醇酰胺。在本研究中，我们报告了一类新型的，有效的，选择性的和系统活性的FAAH活性抑制剂的设计，合成和构效关系（SAR），我们最近证明它们具有有效的抗焦虑作用在大鼠中。这些化合物的特征在于氨基甲酸酯模板在其O-和N-末端被烷基或芳基取代。大多数化合物抑制FAAH，但不能抑制其他几种丝氨酸水解酶，其效力取决于取代基的大小和形状。最初的SAR研究表明，最佳效能的要求是亲脂性N-烷基取代基（例如正丁基或环己基）和弯曲的O-芳基取代基。此外，氨基甲酸酯基对于活性是必不可少的。对烷基氨基甲酸芳基酯的3D-QSAR分析表明，O-芳基部分的大小和形状与FAAH抑制能力有关。构建了CoMSIA模型，表明与O-苯基环的间位置相对应的区域的空间占据可提
• Modulation of anxiety through blockade of anandamide hydrolysis
  申请人：The Regents of the University of California

  公开号：US20040127518A1

  公开（公告）日：2004-07-01

  Fatty acid amide hydrolase inhibitors of the Formula: 1 are provided wherein X is NH, CH 2 , O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted biphenylyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted phenyl; substituted or unsubstituted terphenylyl; substituted or unsubstituted cycloalkyl, heteroaryl, or alkyl; and R 1 and R 2 are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and substituted or unsubstituted phenyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; with the proviso that if Z is O, one of R 1 and R 2 is absent, and that if Z is N, optionally R 1 and R 2 may optionally be taken together to form a substituted or unsubstituted N-heterocycle or substituted or unsubstituted heteroaryl with the N atom to which they are each attached. Pharmaceutical compositions comprising the compounds of Formula I and methods of using them to inhibit FAAH and/or treat appetite disorders, glaucoma, pain, insomnia, and neurological and psychological disorders including anxiety disorders, epilepsy, and depression are provided.

  本发明提供了公式1中X为NH，CH2，O或S；Q为O或S；Z为O或N；R为从取代或未取代芳基；取代或未取代联苯基；取代或未取代萘基；取代或未取代苯基；取代或未取代三苯基基；取代或未取代环烷基，杂环芳基或烷基中选择的芳香基；R1和R2分别独立地选择从H，取代或未取代烷基，取代或未取代杂环烷基和取代或未取代苯基，取代或未取代联苯基，取代或未取代芳基和取代或未取代杂环芳基的群中选择；但是如果Z为O，则R1和R2中的一个不存在，如果Z为N，则R1和R2可以选择性地一起形成取代或未取代的N-杂环或取代或未取代的杂环芳基，与它们各自连接的N原子。本发明还提供了包括公式I中化合物的制药组合物以及使用它们来抑制FAAH和/或治疗食欲障碍，青光眼，疼痛，失眠和神经心理障碍，包括焦虑症，癫痫和抑郁症的方法。
• MODULATION OF ANXIETY THROUGH BLOCKADE OF ANANDAMIDE HYDROLYSIS
  申请人：Piomelli Daniele

  公开号：US20120010283A1

  公开（公告）日：2012-01-12

  Fatty acid amide hydrolase inhibitors of the Formula: are provided wherein X is NH, CH 2 , O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted biphenylyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted phenyl; substituted or unsubstituted terphenylyl; substituted or unsubstituted cycloalkyl, heteroaryl, or alkyl; and R 1 and R 2 are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and substituted or unsubstituted phenyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; with the proviso that if Z is O, one of R 1 and R 2 is absent, and that if Z is N, optionally R 1 and R 2 may optionally be taken together to form a substituted or unsubstituted N-heterocycle or substituted or unsubstituted heteroaryl with the N atom to which they are each attached. Pharmaceutical compositions comprising the compounds of Formula I and methods of using them to inhibit FAAH and/or treat appetite disorders, glaucoma, pain, insomnia, and neurological and psychological disorders including anxiety disorders, epilepsy, and depression are provided.

  提供了公式为的脂肪酸酰胺水解酶抑制剂：其中X为NH，CH2，O或S；Q为O或S；Z为O或N；R为从取代或未取代芳基；取代或未取代联苯基；取代或未取代萘基；取代或未取代苯基；取代或未取代三苯基基；取代或未取代环烷基，杂环芳基或烷基中选择的芳香基；R1和R2分别选择自H，取代或未取代烷基，取代或未取代杂环烷基，取代或未取代苯基，取代或未取代联苯基，取代或未取代芳基和取代或未取代杂环芳基的群中；但是如果Z为O，则R1和R2中的一个不存在，如果Z为N，则可选地将R1和R2结合在一起形成取代或未取代的N-杂环或取代或未取代的杂环芳基，与它们各自连接的N原子。提供了包含公式I化合物的制药组合物以及使用它们来抑制FAAH和/或治疗食欲障碍，青光眼，疼痛，失眠以及神经和心理障碍，包括焦虑症，癫痫和抑郁症的方法。
• PERIPHERALLY RESTRICTED FAAH INHIBITORS
  申请人：Piomelli Daniele

  公开号：US20130217764A1

  公开（公告）日：2013-08-22

  Peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH) are provided. The compounds can suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). Despite their relative inability to access brain and spinal cord, the compounds attenuate behavioral responses indicative of persistent pain in rodent models of inflammation and peripheral nerve injury, and suppresses noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CBi receptor blockade prevents these effects. Accordingly, the invention also provides methods, and pharmaceutical compositions for treating conditions in which the inhibition of peripheral FAAH would be of benefit. The compounds of the invention are according to the formula (I): in which R 1 is a polar group. In some embodiments, R 1 is selected from the group consisting of hydroxy and the physiologically hydro lysable esters thereof. R 2 and R 3 are independently selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbyl; each R 4 is independently selected from the group consisting of halogen and substituted or unsubstituted hydrocarbyl and n is an integer from 0 to 4; each R 5 is independently selected from the group consisting of halo and substituted or unsubstituted hydrocarbyl and m is an integer from 0 to 3; and R 6 is substituted or unsubstituted cyclohexyl; and the pharmaceutically acceptable salts thereof.

  本发明提供了周围限制的脂肪酸酰胺酶（FAAH）抑制剂。这些化合物可以抑制FAAH活性并增加中枢神经系统（CNS）外的阿那and胺水平。尽管它们相对无法进入大脑和脊髓，但这些化合物可以减弱炎症和周围神经损伤啮齿动物模型中表现持续性疼痛的行为反应，并抑制与伤害处理有关的脊髓区域的神经元激活。CB1受体阻断可以防止这些效应。因此，本发明还提供了治疗抑制周围FAAH会有益的疾病的方法和制药组合物。本发明的化合物符合以下公式（I）：其中R1是极性基团。在某些实施例中，R1选择自羟基和其生理上可水解的酯。R2和R3分别选择自氢和取代或未取代的烃基；每个R4独立选择自卤素和取代或未取代的烃基，n为0到4的整数；每个R5独立选择自卤素和取代或未取代的烃基，m为0到3的整数；R6是取代或未取代的环己基；以及其药物可接受的盐。
• Inhibitors for the Soluble Epoxide Hydrolase
  申请人：HAMMOCK BRUCE D.

  公开号：US20110021448A1

  公开（公告）日：2011-01-27

  Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases.

  提供了可用于治疗疾病的可溶性环氧酶（sEH）抑制剂，其中包含多个药效团。