N-phenethyl-α-methyl-(RS)-tryptophanamine | 114779-47-4

• 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: N-phenethyl-α-methyl-(RS)-tryptophanamine
• 英文别名: DL-α-methyl tryptophanyl-2-phenethylamide；(2-phenylethyl)amine；α-methyl-RS-tryptophanyl-2-phenethylamide；α-amino-α-methyl-N-(2-phenylethyl)-1H-indole-3-propanamide；(+/-)-alpha-amino-alpha-methyl-N-(2-phenylethyl)-1H-indole-3-propanamide；2-amino-3-(1H-indol-3-yl)-2-methyl-N-(2-phenylethyl)propanamide
• CAS: 114779-47-4
• 化学式: C₂₀H₂₃N₃O
• 分子量: 321.422
• InChiKey: HWVRVHADTYSJFD-UHFFFAOYSA-N

物化性质

• 熔点：
  104-106 °C
• 沸点：
  604.3±55.0 °C(predicted)
• 密度：
  1.185±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.9
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-phenethyl-α-methyl-(RS)-tryptophanamine 、 氯甲酸环己酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以74%的产率得到(+/-)-carbamic acid<1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-<(2-phenylethyl)amino>ethyl>cyclohexyl ester
  参考文献：
  名称：

  胆囊收缩素二肽拮抗剂：某些新型CCK-A和CCK-B选择性和“混合” CCK-A / CCK-B拮抗剂的设计，合成和抗焦虑特性。

  摘要：

  描述了开发胆囊收缩素（CCK）受体亚型CCK-A和CCK-B的选择性二肽配体的设计，合成和结构活性关系（SAR）。开发的SAR用于设计对CCK-A和CCK-B受体均具有相同纳摩尔结合亲和力的配体。示例化合物，例如[1R- [1 alpha [R *（R *）]，2 beta]]-4-[[2-[[3-（1H-吲哚-3-基）-2-甲基-2- [[[（（2-甲基环己基）氧基]羰基]氨基] -1-氧丙基]-氨基] -1-苯基乙基]氨基] -4-氧代丁酸（24c），（1R-反式）-N-α -甲基-N-[[（（2-甲基环己基）氧基]羰基] -D-色氨酸] -L-3-（苯甲基）-β-丙氨酸（28i）和N- [α-甲基-N-[（三环） [3.3.1.1]癸-2-基氧基）羰基] -D-色氨酸] -L-3-（苯甲基）-β-丙氨酸（30m）是具有CCK-B结合亲和力为IC50 = 3.9的CCK-B选择性化合物，

  DOI：

  10.1021/jm00057a005
• 作为产物：
  描述：

  Alpha-甲基-DL-色氨酸 在 哌啶 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.25h， 生成 N-phenethyl-α-methyl-(RS)-tryptophanamine
  参考文献：
  名称：

  Cholecystokinin peptidomimetics as selective CCK-B antagonists: Design, synthesis, and in vitro and in vivo biochemical properties

  摘要：

  Antagonists of cholecystokinin-B (CCK-B) receptors have been shown to alleviate CCK4-induced panic attacks in humans and to potentiate opioid effects in animals. The clinical use of these compounds is critically dependent on their ability to cross the blood-brain barrier. In order to improve this property, new, peptoid-derived CCK-B antagonists, endowed with high affinity, selectivity, and increased lipophilicity have been developed. The affinity and selectivity of these compounds have been characterized in vitro and in vivo using guinea pig, rat, and mouse. Most of these compounds proved to be selective for the CCK-B receptor, the most potent analog, N-[N-[(2-adamantyloxy)carbonyl]-D-alpha-methyltryptophanyl]-N-[2-(4-chlorophenyl)ethyl]glycine (26A), having a K(i) value of 6.1 nM for guinea pig cortex membranes in vitro and a good selectivity ratio (K(i) CCK-A/K(i) CCK-B = 174). Furthermore, the in vivo affinity of 26A for mouse brain CCK-B receptors, following intracerebroventricular injection at different concentrations, was found to be 10 nmol. Using competition experiments with the specific CCK-B ligand [H-3]pBC 264, compound 26A was shown to cross the blood-brain barrier (0.2%) after intraperitoneal administration in mice. This compound is therefore an interesting pharmacological tool to further elucidate the physiopathological role of endogenous CCK.

  DOI：

  10.1021/jm00072a005

文献信息

• 2-substituted-[2-substituted-amino]-N-arylalkyl-3-[indol-3-yl]
  申请人：Warner-Lambert Company

  公开号：US04757151A1

  公开（公告）日：1988-07-12

  Certain 2-substituted-[2-substituted-amino]-N-arylalkyl-3-[indol-3-yl]propanamides demonstrate activity as appetite suppressants. The compounds, pharmaceutical compositions, and a method of suppressing appetite are disclosed.

  某些2-取代-[2-取代氨基]-N-芳基烷基-3-[吲哚-3-基]丙酰胺表现出作为食欲抑制剂的活性。该化合物、药物组合物和抑制食欲的方法已被披露。
• N-substituted cycloalkyl and polycycloalkyl .alpha.-substituted Trp-Phe-
  申请人：Warner-Lambert Company

  公开号：US05622983A1

  公开（公告）日：1997-04-22

  Novel unnatural dipeptoids of .alpha.-substituted Trp-Phe derivatives useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, colorectal tumors, or as antipsychotics are disclosed. Further the compounds are antianxiety agents, antiulcer agents, antidepressant agents, and are agents useful for preventing the withdrawal response produced by chronic treatment or use followed by chronic treatment followed by withdrawal from nicotine, diazepam, alcohol, cocaine, caffeine, or opiods. Also disclosed are pharmaceutical compositions and methods of treatment using the dipeptoids as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds to prepare pharmaceutical and diagnostic compositions.

  本发明涉及一种新颖的非天然二肽类α-取代Trp-Phe衍生物，可用作治疗肥胖症、肠道胃酸过多、胃泌素依赖性肿瘤、结肠癌或作为抗精神病药物。此外，这些化合物还具有抗焦虑、抗溃疡、抗抑郁作用，并可用于预防尼古丁、安定、酒精、可卡因、咖啡因或阿片类药物的长期治疗或使用后出现的戒断反应。本发明还涉及使用这些二肽类化合物制备药物和诊断组合物的方法。同时，本发明还涉及制备这些化合物的方法以及在制备中有用的新型中间体。
• Treatment of pain and colorectal cancer with dipeptoids of
  申请人：Warner-Lambert Company

  公开号：US05580896A1

  公开（公告）日：1996-12-03

  This invention relates to the treatment of pain and inhibiting the growth of colorectal cancer with dipeptoids of .alpha.-substituted Trp-Phe derivatives.

  本发明涉及使用α-取代的Trp-Phe二肽衍生物治疗疼痛和抑制结直肠癌生长。
• 2-Substituted-[2-substituted-amino]-N-aralkyl-3-[indol-3-yl]propanamides
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0224151A2

  公开（公告）日：1987-06-03

  Certain 2-substituted-[2-substituted-aminol-N-arylalkyl-3-[indo]-3-yl]propanamides demonstrate activity as appetite suppressants. The compounds, pharmaceutical compositions, and a method of suppressing appetite are disclosed.

  某些 2-取代-[2-取代-氨基醇-N-芳基烷基-3-[吲哚]-3-基]丙酰胺具有抑制食欲的活性。 本文公开了这些化合物、药物组合物和一种抑制食欲的方法。
• Rationally designed ‘dipeptoid’ analogues of cholecystokinin (CCK): N-terminal structure-affinity relationships of α-methyl-tryptophan derivatives
  作者：JM Eden、M Higginbottom、DR Hill、DC Horwell、JC Hunter、K Martin、MC Pritchard、SS Rahman、RS Richardson、E Roberts

  DOI：10.1016/0223-5234(93)90077-r

  日期：1993.1

  The structure-affinity relationships (SAR) between the N-terminii of a series of alpha-methyl-tryptophanylphenethylamide derivatives and the cholecystokinin (CCK) B receptor are discussed. A series of compounds with the general formula R-X-alpha-methyl-tryptophanylphenethylamide was prepared, where R is a cycloalkyl, a bicycloalkyl or a tricycloalkyl group and X is a urethane, thiourethane, amide, urea or a sulphinamide linking group. The CCK-B receptor binding affinities of these are discussed. The SAR form part of a systematic program for the rational design of 'dipeptoid' analogues of the neuropeptide CCK. Beginning with 1,1-dimethylpropyl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamate (IC50 = 4720 nM on CCK-B binding affinity) the N-terminal moiety was systematically changed for groups of varying size, shape and lipophilicity until the optimal N-terminal group was obtained and the favoured linking group chosen, resulting in the compound tricyclo[3.3.1.1(3,7)]dec-2-yl(R)-[(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[(2-phenylethyl)amino]ethyl]carbamate with an IC50 = 32 nM on CCK-B receptor binding affinity.