(S)-1-propylamino-1-phenylbutane | 391233-85-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (S)-1-propylamino-1-phenylbutane
• 英文别名: (1S)-1-phenyl-N-propylbutan-1-amine
• CAS: 391233-85-5
• 化学式: C₁₃H₂₁N
• 分子量: 191.316
• InChiKey: FWIHMKRULOLWKW-ZDUSSCGKSA-N

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：

  (S)-1-propylamino-1-phenylbutane 在 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 生成
  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：

  (R)-(+)-1-苯基-1-丁醇 在 palladium on activated charcoal lithium aluminium tetrahydride 、 二苯基膦叠氮化物 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 27.0h， 生成 (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

• TRYPHOSTIN-ANALOGS FOR THE TREATMENT OF CELL PROLIFERATIVE DISEASES
  申请人：Donato Nicholas J

  公开号：US20100292229A1

  公开（公告）日：2010-11-18

  The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. In general aspects, compounds of the present invention are tyrphostin-like in structure. Compounds of the present invention, in certain embodiments, display significant potency by causing, for example, inhibition of Stat3 activation, reduction in c-myc protein levels and/or induction of apoptosis in tumor cells. In general aspects, compounds of the present invention induce one or more of these activities at nanomolar concentrations and typically function through a unique mechanism involving the induction of stress granules that bind specific signaling molecules and prevent them from participating in signal transduction and oncogenesis.

  本发明涉及化合物及其用于治疗细胞增殖性疾病，如癌症。在一般方面，本发明的化合物在结构上类似于酪氨酸激酶抑制剂。在某些实施例中，本发明的化合物通过诱导应激颗粒结合特定信号分子并阻止它们参与信号转导和肿瘤发生，从而表现出显著的效力，例如抑制Stat3激活、降低c-myc蛋白水平和/或诱导肿瘤细胞凋亡。在一般方面，本发明的化合物在纳摩尔浓度下诱导这些活性中的一个或多个，并通常通过诱导应激颗粒的独特机制发挥作用，这些应激颗粒结合特定信号分子并防止它们参与信号转导和肿瘤发生。
• Rational Design, Synthesis, and Structure−Activity Relationships of Aryltriazoles as Novel Corticotropin-Releasing Factor-1 Receptor Antagonists
  作者：Richard F. Lowe、Jodene Nelson、Trunghau N. Dang、Paul D. Crowe、Anil Pahuja、James R. McCarthy、Dimitri E. Grigoriadis、Paul Conlon、John Saunders、Chen、Thomas Szabo、Ta Kung Chen、Haig Bozigian

  DOI：10.1021/jm049339c

  日期：2005.3.1

  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.