(4-fluorophenyl)-1-[1-(cis-4-isopropylcyclohexyl)piperidin-4-ylidene]amine | 494863-86-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (4-fluorophenyl)-1-[1-(cis-4-isopropylcyclohexyl)piperidin-4-ylidene]amine
• 英文别名: (4-Fluoro-phenyl)-[1-(cis-4-isopropyl-cyclohexyl)-piperidin-4-ylidene]-amin
• CAS: 494863-86-4
• 化学式: C₂₀H₂₉FN₂
• 分子量: 316.462
• InChiKey: LBOAYFHKDFMWHH-MOBUCQHHSA-N

物化性质

• 沸点：
  403.9±45.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.21
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  15.6
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (4-fluorophenyl)-1-[1-(cis-4-isopropylcyclohexyl)piperidin-4-ylidene]amine 在 三苯基膦 、 cesium fluoride 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 45.0h， 生成 (3'aRS,6'aSR)-5'-cyclopropylmethyl-2'-(4-fluorophenyl)-1-(cis-4-isopropylcyclohexyl)hexahydrospiro[piperidine-4,1'-pyrrolo[3,4-c]pyrrole]-4',6'-dione
  参考文献：
  名称：

  Novel Hexahydrospiro[piperidine-4,1‘-pyrrolo[3,4-c]pyrroles]:  Highly Selective Small-Molecule Nociceptin/Orphanin FQ Receptor Agonists

  摘要：

  Novel hexahydrospiro[piperidine-4,1'-pyrrolo[3,4-c]pyrroles that act as potent and selective orphanin FQ/nociceptin (N/OFQ) receptor (NOP) agonists were identified. The best compound, (+)-5a, potently inhibited H-3-N/OFQ binding to the NOP receptor (K-i = 0.49 nM) but was > 1000-fold less potent in binding to MOP, KOP, and DOP opiate receptors. Further, (+)-5a potently stimulated GTPgammaS binding to NOP membranes (EC50 = 65 nM) and inhibited forskolin-mediated cAMP accumulation in NOP-expressing cells (EC50 = 9.1 nM) with a potency comparable to that of the natural peptide agonist N/OFQ. These results indicate that (+)-5a is a highly selective and potent small-molecule full agonist of the NOP receptor.

  DOI：

  10.1021/jm0209174
• 作为产物：
  描述：

  1-乙基-1-甲基-4-氧代哌啶-1-碘化物 在 4 A molecular sieve 、 potassium carbonate 作用下， 以 正戊烷 为溶剂， 反应 146.0h， 生成 (4-fluorophenyl)-1-[1-(cis-4-isopropylcyclohexyl)piperidin-4-ylidene]amine
  参考文献：
  名称：

  Novel Hexahydrospiro[piperidine-4,1‘-pyrrolo[3,4-c]pyrroles]:  Highly Selective Small-Molecule Nociceptin/Orphanin FQ Receptor Agonists

  摘要：

  Novel hexahydrospiro[piperidine-4,1'-pyrrolo[3,4-c]pyrroles that act as potent and selective orphanin FQ/nociceptin (N/OFQ) receptor (NOP) agonists were identified. The best compound, (+)-5a, potently inhibited H-3-N/OFQ binding to the NOP receptor (K-i = 0.49 nM) but was > 1000-fold less potent in binding to MOP, KOP, and DOP opiate receptors. Further, (+)-5a potently stimulated GTPgammaS binding to NOP membranes (EC50 = 65 nM) and inhibited forskolin-mediated cAMP accumulation in NOP-expressing cells (EC50 = 9.1 nM) with a potency comparable to that of the natural peptide agonist N/OFQ. These results indicate that (+)-5a is a highly selective and potent small-molecule full agonist of the NOP receptor.

  DOI：

  10.1021/jm0209174

文献信息

• Spiro[piperidine-4,1'-pyrrolo [3,4-C] pyrrole]derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06075034A1

  公开（公告）日：2000-06-13

  The present invention relates to compounds of the general formula wherein R.sup.1 is C.sub.5-12 -cycloalkyl, optionally substituted by lower alkyl; decahydro-naphthalen-1-yl; decahydro-naphthalen-2-yl; indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; decahydro-azulen-2-yl; bicyclo[6.2.0]dec-9-yl; acenaphthen-1-yl; bicyclo[3.3.1]non-9-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl; octahydro-inden-2-yl; 1,2,3,4-tetrahydro-naphthalen-1-yl; 1,2,3,4-tetrahydro-naphthalen-2-yl; naphthalen-lower alkyl-1-yl; naphthalen-lower alkyl-2-yl; acenaphthen-1-yl; and 5-isopropyl-2-methyl-bicyclo[3.1.0]hex-3-yl; R.sup.2, R.sup.3 are hydrogen; hydroxy; lower alkyl; .dbd.O; or phenyl, optionally substituted by lower allyl, halogen or alkoxy; R.sup.4 is hydrogen; lower alkyl; --(CH.sub.2).sub.n CH(OH)CF.sub.3 ; --(CH.sub.2).sub.n C.sub.3-6 -cycloalkyl; phenyl; benzyl; tetrahydrofuran-3-yl; --(CH.sub.2).sub.n OCH.sub.2 C.sub.6 H.sub.5 ; --(CH.sub.2).sub.n morpholinyl; 3-methyl-oxetan-3-yl-methyl; --(CH.sub.2).sub.n CH.sub.2 OH; --S(O).sub.2 -lower alkyl; --C(O)-lower alkyl; --C(O)CF.sub.3 ; --C(O)(CH.sub.2).sub.n OCH.sub.3 ; --(CH.sub.2).sub.n C(O)N(lower alkyl).sub.2 ; --S(O).sub.2 heteroaryl; --C(O)heteroaryl; --S(O).sub.2 -phenyl; --S(O).sub.2 --N(lower alkyl).sub.2 ; --C(O)--C.sub.3-6 -cycloalkyl; --C(O)O-phenyl; or --C(O)O-lower alkyl: R.sup.5 is hydrogen; halogen; lower alkyl; trifluoromethyl or lower alkoxy; n is 0-3; and to pharmaceutically acceptable acid addition salts thereof The compounds of formula I and their salts are useful as in the treatment of psychiatric, neurological and physiological disorders.

  本发明涉及一般式化合物，其中R.sup.1是C.sub.5-12-环烷基，可以被较低的烷基取代；十氢萘-1-基；十氢萘-2-基；吲哚-1-基或吲哚-2-基，可以被较低的烷基取代；十氢萜烯-2-基；双环[6.2.0]癸-9-基；乙基萘-1-基；双环[3.3.1]壬-9-基；2,3-二氢-1H-苯并-1-基；2,3,3a,4,5,6-六氢-1H-苯并-1-基；八氢-茚-2-基；1,2,3,4-四氢萘-1-基；1,2,3,4-四氢萘-2-基；萘-较低烷基-1-基；萘-较低烷基-2-基；乙基萘-1-基；和5-异丙基-2-甲基-双环[3.1.0]己-3-基；R.sup.2、R.sup.3是氢；羟基；较低的烷基；.dbd.O；或苯基，可以被较低的烷基、烯丙基、卤素或烷氧基取代；R.sup.4是氢；较低的烷基；--（CH.sub.2).sub.n CH(OH)CF.sub.3；--（CH.sub.2).sub.n C.sub.3-6-环烷基；苯基；苄基；四氢呋喃-3-基；--（CH.sub.2).sub.n OCH.sub.2 C.sub.6 H.sub.5；--（CH.sub.2).sub.n 噻吩基；3-甲基-噁二烷-3-基-甲基；--（CH.sub.2).sub.n CH.sub.2 OH；--S（O）.sub.2-较低的烷基；--C（O）-较低的烷基；--C（O）CF.sub.3；--C（O）（CH.sub.2).sub.n OCH.sub.3；--（CH.sub.2).sub.n C（O）N（较低的烷基）.sub.2；--S（O）.sub.2杂环芳基；--C（O）杂环芳基；--S（O）.sub.2-苯基；--S（O）.sub.2--N（较低的烷基）.sub.2；--C（O）--C.sub.3-6-环烷基；--C（O）O-苯基；或--C（O）O-较低的烷基：R.sup.5是氢；卤素；较低的烷基；三氟甲基或较低的烷氧基；n为0-3；以及其药学上可接受的酸盐。式I化合物及其盐在精神病、神经病和生理疾病的治疗中有用。
• Spiro(piperidine-4,1'-pyrrolo(3,4-c)pyrrole)
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0963987A2

  公开（公告）日：1999-12-15

  The present invention relates to compounds of the general formula    wherein the substituents are described in the application and to pharmaceutically acceptable acid addition salts thereof. The compound of the invention are useful in the treatment of diseases related to the orphanin FQ (OFQ) receptor, which include psychiatric, neurological and physiological disorders, such as anxiety and stress disorders, depression, trauma, memory loss due to Alzheimer's disease or other dementias, deficits in cognition and leaning, epilepsy and convulsions, acute and/or chronic pain conditions, and symptoms of addictive drug withdrawal, control of water balance, Na+ excretion, arterial blood pressure disorders and metabolic disorders such as obesity.

  本发明涉及通式为 其中的取代基见本申请所述，以及其药学上可接受的酸加成盐。 本发明的化合物可用于治疗与孤儿素 FQ（OFQ）受体有关的疾病，这些疾病包括精神、神经和生理疾病，如焦虑和应激障碍、抑郁症、创伤、阿尔茨海默病或其他痴呆症导致的记忆丧失、认知和精益功能障碍、癫痫和抽搐、急性和/或慢性疼痛病症、成瘾性药物戒断症状、水平衡控制、Na+排泄、动脉血压紊乱和代谢紊乱，如肥胖。
• US6075034A
  申请人：——

  公开号：US6075034A

  公开（公告）日：2000-06-13