8-(3-aminopropyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 8-(3-aminopropyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
• 化学式: C₁₆H₂₄N₄O
• 分子量: 288.393
• InChiKey: KYPGAASMKFCIJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(3-aminopropyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 、 N-苄基-D-脯氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.17h， 生成 (D)-1-benzylpyrrolidine-2-carboxylic-[3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)propyl]amide
  参考文献：
  名称：

  Structure–activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide

  摘要：

  Twelve derivatives of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide (Comp 24) were synthesised and tested in binding experiments performed on CHOhNOP cell membranes. Among them, a novel interesting NOP receptor antagonist (compound 35) was identified by blending chemical moieties taken from different NOP receptor ligands. In vitro in various assays, Compound 35 consistently behaved as a pure, highly potent (pA(2) in the range 8.0-9.9), competitive and NOP selective antagonist. However compound 35 was found inactive when challenged against N/OFQ in vivo in the mouse tail withdrawal assay. Thus the usefulness of the novel NOP ligand compound 35 is limited to in vitro investigations. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.068
• 作为产物：
  描述：

  [3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)propyl]carbamic acid tert-butyl ester 在 三氟乙酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 以100%的产率得到8-(3-aminopropyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
  参考文献：
  名称：

  Structure–activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide

  摘要：

  Twelve derivatives of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide (Comp 24) were synthesised and tested in binding experiments performed on CHOhNOP cell membranes. Among them, a novel interesting NOP receptor antagonist (compound 35) was identified by blending chemical moieties taken from different NOP receptor ligands. In vitro in various assays, Compound 35 consistently behaved as a pure, highly potent (pA(2) in the range 8.0-9.9), competitive and NOP selective antagonist. However compound 35 was found inactive when challenged against N/OFQ in vivo in the mouse tail withdrawal assay. Thus the usefulness of the novel NOP ligand compound 35 is limited to in vitro investigations. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.068

文献信息

• Dihydropyridines and new uses thereof
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US05767131A1

  公开（公告）日：1998-06-16

  The invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound having the structure: ##STR1## wherein Y is --(CH.sub.2).sub.n --, where n is 1, 2, 3, 4 or 5; --(CH.sub.2).sub.h --O--(CH.sub.2).sub.k --, where h and k are independently the same or different and are 2, 3 or 4; --(CH.sub.2).sub.h --CH.dbd.CH--(CH.sub.2).sub.k --; or --(CH.sub.2).sub.h --C.tbd.C--(CH.sub.2).sub.k --, where h and k are independently the same or different and are 1, 2, 3 or 4; wherein Z is O, NH, or CH.sub.2 ; wherein R.sup.1 is a linear or branched chain alkyl, alkoxyalkyl or arylalkyl group; wherein R.sup.2 and R.sup.4 are independently the same or different and are H, or a linear or branched chain alkyl group; wherein R.sup.3 is H, a linear or branched chain alkyl, alkoxy, alkoxyalkyl or acyl group; and wherein R.sup.5 and R.sup.6 are independently the same or different and are H, OH, Cl, Br, F, NO.sub.2, CN, CF.sub.3, or NH.sub.2, or a linear or branched chain alkyl, alkoxy, alkoxycarbonyl, acyl, alkylsulfoxide, alkylsulfone, or mono- or dialkylamino group. Other active compounds containing one, two or three rings are also disclosed as well as pharmaceutical compositions prepared therefrom and methods of use in the treatment of BPH, inhibition of cholesterol synthesis, and reduction of intraocular pressure.

  该发明提供了一种治疗良性前列腺增生的方法，包括向受试者施用具有以下结构的化合物的治疗有效量： 其中Y为--(CH.sub.2).sub.n --，其中n为1、2、3、4或5；--(CH.sub.2).sub.h --O--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为2、3或4；--(CH.sub.2).sub.h --CH.dbd.CH--(CH.sub.2).sub.k --；或--(CH.sub.2).sub.h --C.tbd.C--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为1、2、3或4；其中Z为O、NH或CH.sub.2；其中R.sup.1为线性或支链烷基、烷氧基烷基或芳基烷基；其中R.sup.2和R.sup.4独立且相同或不同，为H，或线性或支链烷基；其中R.sup.3为H、线性或支链烷基、烷氧基、烷氧基烷基或酰基；其中R.sup.5和R.sup.6独立且相同或不同，为H、OH、Cl、Br、F、NO.sub.2、CN、CF.sub.3或NH.sub.2，或线性或支链烷基、烷氧基、烷氧羰基、酰基、烷基亚砜、烷基砜、或单烷基或二烷基氨基基团。还公开了含有一、两个或三个环的其他活性化合物，以及由此制备的药物组合物和在治疗BPH、抑制胆固醇合成和降低眼压中的使用方法。
• US6211198B1
  申请人：——

  公开号：US6211198B1

  公开（公告）日：2001-04-03
• US6310076B1
  申请人：——

  公开号：US6310076B1

  公开（公告）日：2001-10-30
• US6608086B2
  申请人：——

  公开号：US6608086B2

  公开（公告）日：2003-08-19
• [EN] DIHYDROPYRIDINES AND NEW USES THEREOF<br/>[FR] DIHYDROPYRIDINES ET LEURS NOUVELLES UTILISATIONS
  申请人：——

  公开号：WO1994022829A2

  公开（公告）日：1994-10-13

  [EN] The invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound having structure (I) wherein Y is -(CH2)n-, where n is 1, 2, 3, 4 or 5; -(CH2)h-O-(CH2)k-, where h and k are independently the same or different and are 2, 3 or 4; -(CH2)h-CH=CH-(CH2)k-; or -(CH2)h-CC-(CH2)k-, where h and k are independently the same or different and are 1, 2, 3 or 4; wherein Z is 0, NH, or CH2; wherein R<1> is a linear or branched chain alkyl, alkoxyalkyl or arylalkyl group; wherein R<2> and R<4> are independently the same or different and are H, or a linear or branched chain alkyl group; wherein R<3> is H, a linear or branched chain alkyl, alkoxy, alkoxyalkyl or acyl group; and wherein R<5> and R<6> are independently the same or different and are H, OH, Cl, Br, F, No2, CN, CF3, or NH2, or a linear or branched chain alkyl, alkoxy, alkoxycarbonyl, acyl, alkylsulfoxide, alkylsulfone, or mono- or dialkylamino group. Other active compounds containing one, two or three rings are also disclosed as well as pharmaceutical compositions prepared therefrom and methods of use in the treatment of BPH, inhibition of cholesterol synthesis, and reduction of intraocular pressure.
  [FR] Méthode de traitement de l'hyperplasie prostatique bénigne par administration d'une dose à effet thérapeutique d'un composé de structure (I), où Y représente -(CH2)n- où n est égal à 1, 2, 3, 4 ou 5; -(CH2)h-O-(CH2)k, où h et k sont indépendamment identiques ou différents et égaux à 2, 3 ou 4; -(CH2)h-CH=CH-(CH2)k; ou -(CH2)h-CC-(CH2)k- où h et k sont indépendamment identiques ou différents et égaux à 1, 2, 3, ou 4; où Z représente O, NH ou CH2; où R1 représente un groupe alkyle, alcoxyalkyle ou arylalkyle linéaire ou à chaîne ramifiée; où R2 et R4 sont indépendamment identiques ou différents et représentent H ou un groupe alkyle linéaire ou à chaîne ramifiée; où R3 représente H, un groupe alkyle, alcoxy, alcoxyalkyle ou acyle linéaire ou à chaîne ramifiée; où R5 et R6 sont indépendamment identiques ou différents et représentent H, OH, Cl, Br, F, HO2, CN, CF3 ou NH2, ou un groupe alkyle, alcoxy, alcoxycarbonyle, acyle, alkylsulfoxyde, alkylsulfone linéaire ou à chaîne ramifiée, ou un groupe mono ou dialkylamino. D'autres composés actifs à un, deux, ou trois cycles sont également présentés ainsi que des préparations pharmaceutiques les contenant et leurs procédés d'utilisation dans le traitement de l'HPB, l'inhibition de la synthèse du cholestérol, et la réduction de la pression intraoculaire.