1-(4-fluorophenyl)-N-methyl-3-(piperidin-4-yl)-1H-indole-5-carboxamide | 330944-17-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(4-fluorophenyl)-N-methyl-3-(piperidin-4-yl)-1H-indole-5-carboxamide
• 英文别名: 1-(4-fluorophenyl)-N-methyl-3-piperidin-4-ylindole-5-carboxamide
• CAS: 330944-17-7
• 化学式: C₂₁H₂₂FN₃O
• 分子量: 351.424
• InChiKey: JQHIFMFIECIRJD-UHFFFAOYSA-N

物化性质

• 沸点：
  512.2±50.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-N-methyl-3-(piperidin-4-yl)-1H-indole-5-carboxamide 在 lithium aluminium tetrahydride 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 11.0h， 生成 1-[2-[4-[1-(4-Fluorophenyl)-5-methylaminomethyl-1H-indol-3-yl]-1-piperidinyl]ethyl]-2-imidazolidinon
  参考文献：
  名称：

  抗精神病药sertindole的5-氨基甲基和5-氨基甲酰基类似物的合成及结构亲和关系研究。一类新的选择性α1肾上腺素受体拮抗剂。

  摘要：

  描述了一种新型的选择性α（1）肾上腺素能受体拮抗剂，其源自抗精神病药塞多度。最有效和选择性最大的化合物1-（2-（4- [5-氨基甲基-1-（4-氟苯基）-1H-吲哚-3-基] -1-哌啶基）乙基）-2-咪唑啉酮（11）结合对α（1）肾上腺素受体具有0.50 nM的亲和力，对多巴胺D（2），D（3），D（4）和5-羟色胺5-HT（1A），5-HT（1B）的亲和力低44倍以上，5-HT（2A）和5-HT（2C）受体。讨论了为肾上腺素α（1）受体提供高亲和力和对多巴胺D（2）和5-羟色胺5-HT（2A）和5-HT（2C）受体的高选择性的分子特征。

  DOI：

  10.1016/s0968-0896(02)00459-5
• 作为产物：
  描述：

  1-(4-fluorophenyl)-N-methyl-1H-indole-5-carboxamide 在 platinum(IV) oxide 氢气 、 三氟乙酸 作用下， 以 溶剂黄146 、 三氟乙酸 为溶剂， 20.0 ℃ 、294.18 kPa 条件下， 反应 6.5h， 生成 1-(4-fluorophenyl)-N-methyl-3-(piperidin-4-yl)-1H-indole-5-carboxamide
  参考文献：
  名称：

  抗精神病药sertindole的5-氨基甲基和5-氨基甲酰基类似物的合成及结构亲和关系研究。一类新的选择性α1肾上腺素受体拮抗剂。

  摘要：

  描述了一种新型的选择性α（1）肾上腺素能受体拮抗剂，其源自抗精神病药塞多度。最有效和选择性最大的化合物1-（2-（4- [5-氨基甲基-1-（4-氟苯基）-1H-吲哚-3-基] -1-哌啶基）乙基）-2-咪唑啉酮（11）结合对α（1）肾上腺素受体具有0.50 nM的亲和力，对多巴胺D（2），D（3），D（4）和5-羟色胺5-HT（1A），5-HT（1B）的亲和力低44倍以上，5-HT（2A）和5-HT（2C）受体。讨论了为肾上腺素α（1）受体提供高亲和力和对多巴胺D（2）和5-羟色胺5-HT（2A）和5-HT（2C）受体的高选择性的分子特征。

  DOI：

  10.1016/s0968-0896(02)00459-5

文献信息

• 5-aminoalkyl and 5-aminocarbonyl substituted indoles
  申请人：H. Lundbeck A/S

  公开号：US20020169169A1

  公开（公告）日：2002-11-14

  1 The present invention relates to 5-aminoalkyl and 5-aminocarbonyl substituted indole derivatives having formula (1), wherein R 1 is-(CH 2 ) n-1 -CONR 10 R 11 , -(CH 2 ) n -CONR 10 R 11 or (a), wherein R 10 and R 11 independently are selected from substituents defined herein; n is 1 to 3 and q is 2 to 5; G is N, C, or CH; Ar is phenyl optionally substituted with one or more substituents, or Ar is heterocyclic; R 2 , R 3 , R 4 , R 5 and R 6 are independently selected from substituents defined herein; m is an integer from 2-6; W is O or S; U is N or CH; Z is —(CH 2 ) p -, p being 2 or 3, or Z is —CH═CH—or 1 ,2-phenylene, or Z is—COCH 2 - or —CSCH 2 -; V is O, S, CH 2 , or NR 9 ; X is N, C, or CH; Y is N, C, or CH; provided at least one of X and Y is N; or a pharmaceutically acceptable acid addition salt thereof. The novel 5-substituted indoles have high affinity for &agr; 1 -adrenoceptors and are considered useful for the treatment of diseases or disorders responsive to &agr; 1 -adrenoceptor antagonists. Further, as the compounds are selective &agr; 1 -adrenoceptor ligands they may be particularly useflul as PET or SPECT ligands.

  本发明涉及具有公式（1）的5-氨基烷基和5-氨基羰基取代的吲哚衍生物，其中R1是-(CH2)n-1-CONR10R11，-(CH2)n-CONR10R11或（a），其中R10和R11独立地选择自此处定义的取代基；n为1至3，q为2至5；G为N、C或CH；Ar为苯基，可以选择一个或多个取代基进行取代，或Ar为杂环基；R2、R3、R4、R5和R6独立地选择自此处定义的取代基；m是2-6的整数；W为O或S；U为N或CH；Z为-（CH2）p-，其中p为2或3，或Z为-CH=CH-或1,2-苯基，或Z为-COCH2-或-CSCH2-；V为O、S、CH2或NR9；X为N、C或CH；Y为N、C或CH；其中至少一个为N；或其药学可接受的酸加合物。这些新型的5-取代吲哚具有高亲和力的α1-肾上腺素受体，被认为对于对α1-肾上腺素受体拮抗剂有反应的疾病或疾病的治疗有用。此外，由于这些化合物是选择性的α1-肾上腺素受体配体，它们可能特别有用作PET或SPECT配体。
• 5-AMINOALKYL AND 5-AMINOCARBONYL SUBSTITUTED INDOLES
  申请人：H. LUNDBECK A/S

  公开号：EP1214312B1

  公开（公告）日：2004-04-14
• US6833376B2
  申请人：——

  公开号：US6833376B2

  公开（公告）日：2004-12-21
• [EN] 5-AMINOALKYL AND 5-AMINOCARBONYL SUBSTITUTED INDOLES<br/>[FR] INDOLES SUBSTITUES 5-AMINOALKYLE ET 5-AMINOCARBONYLE
  申请人：LUNDBECK & CO AS H

  公开号：WO2001021614A1

  公开（公告）日：2001-03-29

  The present invention relates to 5-aminoalkyl and 5-aminocarbonyl substituted indole derivatives having general formula (I), wherein R1 is-(CH¿2?)n-1-CONR?10R11¿, -(CH¿2?)n-NR?10R11¿ or (a), wherein R?10 and R11¿ independently are selected from hydrogen, C¿1-6?-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, aryl-C1-6-alkyl, aryl, acyl, amino-C1-6-alkyl and mono- or di-C1-6-alkylamino-C1-6-alkyl, R?12¿ is hydrogen, or C¿1-6?-alkyl n is 1 to 3 and q is 2 to 5; G is N, C, or CH; the dotted line meaning a bond when G is C, and the dotted line meaning no bond when G is CH, or N; Ar is phenyl optionally substituted with one or more substituents independently selected from halogen, C1-6-alkyl, C1-6-alkoxy, hydroxy, trifluoromethyl and cyano, or Ar is 2-thienyl, 3-thienyl, 2-furanyl, 3-furanyl, 2-thiazolyl, 2-oxazolyl, 2-imidazolyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl; R?2, R3, R4 and R5¿ are independently selected from hydrogen, C¿1-6?-alkyl, C1-6-alkoxy, hydroxy, halogen, trifluoromethyl, nitro, cyano, amino, C1-6-alkylamino and C1-6-dialkylamino; R?6¿ is hydrogen, or C¿3-8?-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, C1-6-alkyl, C2-6-alkenyl or C2-6-alkenyl, which may optionally be substituted with one or two hydroxy groups, any hydroxy group present being optionally esterified with an aliphatic carboxylic acid having from two to twentyfour carbon atoms inclusive, or R?6¿ is a group of Formula (II) or (III): wherein m is an integer from 2-6; W is O, or S; U is N or CH; Z is -(CH¿2?)p-, p being 2 or 3, or Z is -CH=CH- or 1,2-phenylene optionally substituted with halogen or trifluoromethyl, or Z is -COCH2- or -CSCH2-; V is O, S, CH2, or NR?9¿ wherein R9 is hydrogen, or C¿1-6?-alkyl, C2-6-alkenyl or C2-6-alkenyl, which may optionally be substituted with one or two hydroxy groups, or a C3-8-cycloalkyl or C3-8-cycloalkyl-C1-6-alkyl group; X is N, C, or CH; Y is N, C, or CH; provided at least one of X and Y is N; and R?7¿ is hydrogen, or C¿1-6?-alkyl; or a pharmaceutically acceptable acid addition salt thereof. The novel 5-aminoalkyl and 5-aminocarbonyl substituted indoles have high affinity for α1-adrenoceptors and are considered useful for the treatment of diseases or disorders responsive to α1-adrenoceptor antagonists. Further, as the compounds are selective α1-adrenoceptor ligands they may be particularly useful as PET or SPECT ligands.
• Synthesis and structure–affinity relationship investigations of 5-aminomethyl and 5-carbamoyl analogues of the antipsychotic sertindole. A new class of selective α1 adrenoceptor antagonists
  作者：Thomas Balle、Jens Perregaard、Anna K. Larsen、Martha Teresa Ramirez、Karina Krøjer Søby、Tommy Liljefors、Kim Andersen

  DOI：10.1016/s0968-0896(02)00459-5

  日期：2003.3

  A new class of selective alpha(1) adrenoceptor antagonists derived from the antipsychotic drug sertindole is described. The most potent and selective compound 1-(2-(4-[5-aminomethyl-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl)ethyl)-2-imidazolidinone (11) binds with 0.50 nM affinity for alpha(1) adrenergic receptors and with more than 44 times lower affinity for dopamine D(2),D(3), D(4) and serotonin

  描述了一种新型的选择性α（1）肾上腺素能受体拮抗剂，其源自抗精神病药塞多度。最有效和选择性最大的化合物1-（2-（4- [5-氨基甲基-1-（4-氟苯基）-1H-吲哚-3-基] -1-哌啶基）乙基）-2-咪唑啉酮（11）结合对α（1）肾上腺素受体具有0.50 nM的亲和力，对多巴胺D（2），D（3），D（4）和5-羟色胺5-HT（1A），5-HT（1B）的亲和力低44倍以上，5-HT（2A）和5-HT（2C）受体。讨论了为肾上腺素α（1）受体提供高亲和力和对多巴胺D（2）和5-羟色胺5-HT（2A）和5-HT（2C）受体的高选择性的分子特征。