(RS)-1-(2,3-dihydro-1H-phenalen-1-yl)-4-phenylamino-piperidine-4-carbonitrile | 309254-69-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 非那烯类
• 英文名称: (RS)-1-(2,3-dihydro-1H-phenalen-1-yl)-4-phenylamino-piperidine-4-carbonitrile
• 英文别名: 4-anilino-1-(2,3-dihydro-1H-phenalen-1-yl)piperidine-4-carbonitrile
• CAS: 309254-69-1
• 化学式: C₂₅H₂₅N₃
• 分子量: 367.494
• InChiKey: BQEQZSBIYJHELT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  39.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲酸 、 (RS)-1-(2,3-dihydro-1H-phenalen-1-yl)-4-phenylamino-piperidine-4-carbonitrile 在 formamide 作用下， 以 乙酸酐 为溶剂， 反应 43.0h， 生成 (RS)-8-(2,3-Dihydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one
  参考文献：
  名称：

  Synthesis of (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonist with anxiolytic-like properties

  摘要：

  The development of 8-(2,3,3a,4,5,6-hexahydro-1H-phenalenl-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-ones 3 starting from (RS)-s-acenaphten-1-yl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 1 is reported. The synthesis and the binding affinities at human OFQ and opioid (mu, kappa, delta) receptors of the stereoisomers 3a-f are described. In vitro the most selective compound, (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1 H-phenalenl-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one 3c, was found to act as a full agonist at the OFQ receptor in the GTP gamma(35)S binding test. It turned out to be selective versus a variety of other neurotransmitter systems. When tested in vivo following intraperitoneal injection, compound 3c was found to decrease neophobia in a novel environment and to exhibit dose-dependent anxiolytic-like effects in the elevated plus-maze procedure, thus confirming the effects observed following intracerebroventricular infusion of the OFQ peptide in rat. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00171-9
• 作为产物：
  描述：

  2,3-Dihydro-phenalen-1-one oxime 在 镍 氨 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 水 、 溶剂黄146 为溶剂， 反应 26.0h， 生成 (RS)-1-(2,3-dihydro-1H-phenalen-1-yl)-4-phenylamino-piperidine-4-carbonitrile
  参考文献：
  名称：

  Synthesis of (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonist with anxiolytic-like properties

  摘要：

  The development of 8-(2,3,3a,4,5,6-hexahydro-1H-phenalenl-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-ones 3 starting from (RS)-s-acenaphten-1-yl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 1 is reported. The synthesis and the binding affinities at human OFQ and opioid (mu, kappa, delta) receptors of the stereoisomers 3a-f are described. In vitro the most selective compound, (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1 H-phenalenl-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one 3c, was found to act as a full agonist at the OFQ receptor in the GTP gamma(35)S binding test. It turned out to be selective versus a variety of other neurotransmitter systems. When tested in vivo following intraperitoneal injection, compound 3c was found to decrease neophobia in a novel environment and to exhibit dose-dependent anxiolytic-like effects in the elevated plus-maze procedure, thus confirming the effects observed following intracerebroventricular infusion of the OFQ peptide in rat. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00171-9

文献信息

• DI-OR TRIAZA-SPIRO [4,5] DECANE DERIVATIVES
  申请人：——

  公开号：US20030176701A1

  公开（公告）日：2003-09-18

  The present invention relates to compounds of the general formula 1 wherein R 1 is C 6-10 -cycloalkyl, optionally substituted by lower alkyl or —C(O)O-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; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl or octahydro-inden-2-yl; R 2 is hydrogen; lower alkyl; ═O or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; 2 is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; X is —CH(OH)—; —C(O)—; —CHR 3 —; —CR 3 ═; —O—; —S—; —CH(COOR 4 )— or —C(COOR 4 )═; Y is —CH 2 —; —CH═; —CH(COOR 4 )—, —C(COOR 4 )═; or —C(CN)—; R 3 is hydrogen or lower alkoxy; R 4 is lower alkyl, cycloalkyl, phenyl, or benzyl and either a or b is optionally an additional bond, and to pharmaceutically acceptable acid addition salts thereof. The compounds are agonists of the orphanin FQ (QFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

  本发明涉及一般式1的化合物， 其中， R1是C6-10环烷基，可选地被较低烷基或-C（O）O-较低烷基取代； 十氢萘-1-基；十氢萘-2-基；吲哚-1-基或吲哚-2-基，可选地被较低烷基取代； 十氢-萜烯-2-基； 双环[6.2.0]癸-9-基； 萘并环[1]苯-1-基； 2,3-二氢-1H-菲-1-基； 2,3,3a,4,5,6-六氢-1H-菲-1-基或八氢-茚-2-基； R2是氢；较低烷基；═O或苯基，可选地被较低烷基，卤素或烷氧基取代； 2是环己基或苯基，可选地被较低烷基，卤素或烷氧基取代； X是—CH（OH）—；—C（O）—；—CHR3—；—CR3═；—O—；—S—；—CH（COOR4）—或—C（COOR4）═； Y是—CH2—；—CH═；—CH（COOR4）—，—C（COOR4）═；或—C（CN）—； R3是氢或较低烷氧基； R4是较低烷基，环烷基，苯基或苯甲基； a或b是可选的额外键，以及其药学上可接受的酸盐。 这些化合物是孤儿受体FQ（QFQ）激动剂，因此在与该受体相关的疾病的治疗中有用。
• Di-or triaza-spiro(4,5)decane derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0963985A2

  公开（公告）日：1999-12-15

  The present invention relates to compounds of the general formula wherein R1is C6-10-cycloalkyl, optionally substituted by lower alkyl or -C(O)O-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; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl or octahydro-inden-2-yl; R2is hydrogen; lower alkyl; =O or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; Ⓐis cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; Xis -CH(OH)-; -C(O)-; -CHR3-; -CR3=; -O-; -S-; -CH(COOR4)- or - C(COOR4)=; Yis -CH2-; -CH=; -CH(COOR4)-, -C(COOR4)=; or -C(CN)-; R3is hydrogen or lower alkoxy; R4is lower alkyl, cycloalkyl, phenyl, or benzyl and either a or b is optionally an additional bond, and to pharmaceutically acceptable acid addition salts thereof. The compounds are agonists and/or antagonists of the orphanin FQ (QFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

  本发明涉及通式如下的化合物 式中 R1为C6-10-环烷基，任选被低级烷基或-C(O)O-低级烷基取代；十氢萘-1-基；十氢萘-2-基；茚-1-基或茚-2-基，任选被低级烷基取代；十氢氮杂环烯-2-基；双环[6.2.0]癸-9-基；苊-1-基；2,3-二氢-1H-苯戊烯-1-基；2,3,3a,4,5,6-六氢-1H-苯戊烯-1-基或八氢-茚-2-基； R2是氢；低级烷基；=O或苯基，可选择被低级烷基、卤素或烷氧基取代； 是环己基或苯基，可选择被低级烷基、卤素或烷氧基取代； X是-CH(OH)-；-C(O)-；-CHR3-；-CR3=；-O-；-S-；-CH(COOR4)-或-C(COOR4)=； Y是-CH2-；-CH=；-CH(COOR4)-，-C(COOR4)=；或-C(CN)-； R3 是氢或低级烷氧基； R4 是低级烷基、环烷基、苯基或苄基 和 a 或 b 是可选的附加键、 及其药学上可接受的酸加成盐。 这些化合物是孤儿素 FQ（QFQ）受体的激动剂和/或拮抗剂，因此可用于治疗与该受体有关的疾病。
• 8-substituted-1,3,8-triazaspiro[4.5]decan-4-on derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0856514B1

  公开（公告）日：2001-06-13
• US6071925A
  申请人：——

  公开号：US6071925A

  公开（公告）日：2000-06-06
• US6642247B2
  申请人：——

  公开号：US6642247B2

  公开（公告）日：2003-11-04