(R,S)-1-propylamino-1-phenylbutane | 92423-91-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R,S)-1-propylamino-1-phenylbutane
• 英文别名: 1-Phenyl-1-propylaminobutan；N-(1-phenylbutyl)-N-propylamine；(+/-)-<1-Phenyl-butyl>-propyl-amin；1-phenyl-N-propylbutan-1-amine
• CAS: 92423-91-1
• 化学式: C₁₃H₂₁N
• 分子量: 191.316
• InChiKey: FWIHMKRULOLWKW-UHFFFAOYSA-N

物化性质

• 沸点：
  87 °C(Press: 1.3 Torr)
• 密度：
  0.8871 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R,S)-1-propylamino-1-phenylbutane 在 sodium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 生成 [5-(4-Methoxy-2-methyl-phenyl)-1-methyl-1H-[1,2,4]triazol-3-yl]-(1-phenyl-butyl)-propyl-amine
  参考文献：
  名称：

  Rational Design, Synthesis, and Structure−Activity Relationships of Aryltriazoles as Novel Corticotropin-Releasing Factor-1 Receptor Antagonists

  摘要：

  Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF1) (e.g., 1, K-i = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated. The compounds were prepared by cyclizations of N-acyl-S-methylisothioureas with alkylhydrazines or by cyclizations with hydrazine followed by alkylation. While members of this series showed potent binding affinity against CRF1 receptor, there were important differences between the different regio- (7 and 12) and stereoisomeric aryltriazoles where the R-1 or R-2 side chain in 7 has an asymmetric center. In terms of overall potency, aryltriazole analogues such as 7r bearing an N-(alpha-branched benzyl)-N-propylamino side chain were the most potent, followed by analogues such as 7a, with an N-bis(cyclopropyl)methyl-N-propylamino side chain, and analogues such as 7m, with an N-(alpha-branched aliphatic)-N-propylamino side chain. While the N-propyl group was crucial for high potency, we hypothesized that the terminal methyl mimicked the 5-methyl of pyrazolo[1,5-alpha]pyrimidines 3 and 4. Correlation of the low-energy conformers of compounds of type 3 and 7 generated by computational analyses was very good. The size and shape of the N-alkyl group dramatically changed the potency of the triazoles, which is in contrast to the SAR seen for bicyclic CRF1 antagonists. In general, the S-enantiomer was much more potent than the corresponding R-isomer. Furthermore, to a limited extent in the aryltriazole series the substituent on the 5-phenyl ring changed the potency up to 9-fold. (S)-1-Methyl-3-[N-(4-fluorophenylpentyl)-N-propyl]amino-5-(2-methoxy-4-dichlorophenyl)-1H-[1,2,4]triazole [(S)-7r] showed very potent binding affinity (K-i = 2.7 nM) to CRF1 receptors with an IC50 of 49 nM in a cAMP inhibition assay.

  DOI：

  10.1021/jm049339c
• 作为产物：
  描述：

  苯丁酮 在 四氯化钛 、 sodium cyanoborohydride 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 16.0h， 生成 (R,S)-1-propylamino-1-phenylbutane
  参考文献：
  名称：

  Rational Design, Synthesis, and Structure−Activity Relationships of Aryltriazoles as Novel Corticotropin-Releasing Factor-1 Receptor Antagonists

  摘要：

  Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF1) (e.g., 1, K-i = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated. The compounds were prepared by cyclizations of N-acyl-S-methylisothioureas with alkylhydrazines or by cyclizations with hydrazine followed by alkylation. While members of this series showed potent binding affinity against CRF1 receptor, there were important differences between the different regio- (7 and 12) and stereoisomeric aryltriazoles where the R-1 or R-2 side chain in 7 has an asymmetric center. In terms of overall potency, aryltriazole analogues such as 7r bearing an N-(alpha-branched benzyl)-N-propylamino side chain were the most potent, followed by analogues such as 7a, with an N-bis(cyclopropyl)methyl-N-propylamino side chain, and analogues such as 7m, with an N-(alpha-branched aliphatic)-N-propylamino side chain. While the N-propyl group was crucial for high potency, we hypothesized that the terminal methyl mimicked the 5-methyl of pyrazolo[1,5-alpha]pyrimidines 3 and 4. Correlation of the low-energy conformers of compounds of type 3 and 7 generated by computational analyses was very good. The size and shape of the N-alkyl group dramatically changed the potency of the triazoles, which is in contrast to the SAR seen for bicyclic CRF1 antagonists. In general, the S-enantiomer was much more potent than the corresponding R-isomer. Furthermore, to a limited extent in the aryltriazole series the substituent on the 5-phenyl ring changed the potency up to 9-fold. (S)-1-Methyl-3-[N-(4-fluorophenylpentyl)-N-propyl]amino-5-(2-methoxy-4-dichlorophenyl)-1H-[1,2,4]triazole [(S)-7r] showed very potent binding affinity (K-i = 2.7 nM) to CRF1 receptors with an IC50 of 49 nM in a cAMP inhibition assay.

  DOI：

  10.1021/jm049339c

文献信息

• Novel branched substituted amino derivatives of 3-amino-1-phenyl-1h-[1,2,4] triazol, methods for producing them and pharmaceutical compositions containing them
  申请人：——

  公开号：US20030162771A1

  公开（公告）日：2003-08-28

  The present invention relates to compounds of formula: 1 in which in particular R 1 , R 2 and R 3 represent, each independently of one another, hydrogen; a halogen atom; a (C 1 -C 5 )alkyl; a (C 1 -C 5 )alkoxy; a trifluoromethyl or an S-R group in which R represents a (C 1 -C 5 )alkyl; R 4 and R 5 represents a (C 1 -C 5 )alkyl; an alkynyl with 3 to 5 carbon atoms; a (C 3 -C 5 )cycloalkyl or an R a —X—(C 1 -C 2 )alkyl group in which R a represents a (C 1 -C 3 )alkyl and X represents O; R 6 represents —CHR 7 R 8 , in which R 7 represents a phenyl group which can be substituted in the 3-, 4- and 5-positions by one or more Z′ radicals, with Z′ representing a halogen; a (C 1 -C 5 )alkyl; a (C 1 -C 5 )alkyl—X— or (C 1 -C 3 )alkyl—X—(C 1 -C 2 )alkyl where X represents O; or a methylenedioxy group; and R 8 represents a (C 1 -C 6 )alkyl; a (C 3 -C 5 )cycloalkyl(C 1 -C 3 )alkyl; or a (C 1 -C 3 )alkyl—X—(C 1 -C 3 )alkyl where X represents O. These compounds have an affinity for CRF receptors.

  本发明涉及以下化合物的公式：1其中特别是R1，R2和R3分别表示氢; 卤素原子; （C1-C5）烷基; （C1-C5）烷氧基; 三氟甲基或S-R基团，其中R表示（C1-C5）烷基; R4和R5表示（C1-C5）烷基; 具有3至5个碳原子的炔基; （C3-C5）环烷基或Ra—X—（C1-C2）烷基，其中Ra表示（C1-C3）烷基，X表示O; R6表示—CHR7R8，其中R7表示苯基，可以在3-，4-和5-位上被一个或多个Z'基取代，其中Z'表示卤素; （C1-C5）烷基; （C1-C5）烷基—X—或（C1-C3）烷基—X—（C1-C2）烷基，其中X表示O; 或甲亚氧基; 和R8表示（C1-C6）烷基; （C3-C5）环烷基（C1-C3）烷基; 或（C1-C3）烷基—X—（C1-C3）烷基，其中X表示O。这些化合物具有与CRF受体的亲和力。
• Huet,J., Bulletin de la Societe Chimique de France, 1964, p. 952 - 960
  作者：Huet,J.

  DOI：——

  日期：——
• NOUVEAUX DERIVES AMINO SUBSTITUES RAMIFIES DU 3-AMINO-1-PHENYL-1H[1,2,4]TRIAZOLE, PROCEDES POUR LEUR PREPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：SANOFI-SYNTHELABO

  公开号：EP1242389A2

  公开（公告）日：2002-09-25
• US6806282B2
  申请人：——

  公开号：US6806282B2

  公开（公告）日：2004-10-19
• [EN] NOVEL BRANCHED SUBSTITUTED AMINO DERIVATIVES OF 3-AMINO-1-PHENYL-H[1,2,4]TRIAZOL, METHODS FOR PRODUCING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX DERIVES AMINO SUBSTITUES RAMIFIES DU 3-AMINO-1-PHENYL-H[1,2 4]TRIAZOLE, PROCEDES POUR LEUR PREPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：SANOFI SYNTHELABO

  公开号：WO2001044207A2

  公开（公告）日：2001-06-21

  La présente invention concerne des composés de formule (I), dans laquelle notamment R1, R2, R3 représentent, chacun indépendamment l'un de l'autre, l'hydrogène, un atome d'halogène; un (C1-C5)alkyle; un (C1-C5)alcoxy; un trifluorométhyle ou un groupe S-R dans lequel R représente un (C1-C5)alkyle; R4, R5 représente un (C1-C5)alkyle; un alcynyle de 3 à 5 atomes de carbone; un (C3-C5)cycloalkyl ou un groupe Ra-X-(C1-C2)alkyle dans lequel Ra représente un (C1-C3)alkyle et X représente O; R6 représente -CHR7R8 dans lequel R7 représente un groupe phényle pouvant être substitué en position 3, 4 et 5 par un ou plusieurs radicaux Z', avec Z' représentant un halogène; un (C1-C5)alkyle; un (C1-C5)alkyl-X- ou (C1-C3)alkyl-X-(C1-C2)alkyle où X représente O; ou un groupe méthylènedioxy; et R8 représente un (C1-C6)alkyle; un (C3-C5)cycloalkyl(C1-C3)alkyle; (C1-C3)alkyl-X-(C1-C3)alkyle où X représente O. Ces composés sont affins pour les récepteurs du CRF.