新的4-amino-5-chloro-2-methoxybenzoic酸酯作为5-HT4强有力的受体激动剂和拮抗剂受体。
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杨D, Soulier JL Sicsic年代,Mathe-Allainmat M, Bremont B,橘黄色T, Cardamone R, Aureggi G, Langlois M
新的4-amino-5-chloro-2-methoxybenzoic酸酯作为5-HT4强有力的受体激动剂和拮抗剂受体。
J地中海化学。1997年2月14日,40(4):608 - 21所示。
- PubMed ID
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9046352 (在PubMed]
- 文摘
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许多来自4-amino-5-chloro-2-methoxybenzoic酸和苯甲酸取代1-piperidineethanol合成和发现强有力的5-HT4受体受体激动剂在电刺激肌间神经丛和豚鼠回肠的纵肌和大鼠食道肌肉。单基取代的哌啶环与我,哦,NH-Ac,或CONH2组给化合物均等的7(10302毫升),5-HT4受体激动剂之前报道摩尔亲和力。7,k是一样有效的5 -羟色胺(5 -)但是有最大的反应只有5 - 60 - 80%,表明这些化合物的部分激动剂配置文件。绑定化验进行[3 h] GR 113808大鼠纹状体,和这些化合物被发现的几个摩尔亲和力5-HT4受体(7,Ki = 1.07 + / - 0.5 nM;7 k, Ki = 1.0 + / - 0.3海里)。哌啶环上的两个甲基的引入带来了戏剧性的变化在药理的2 - [(cis, trans-3 5-dimethylpiperidinyl)乙基]4-amino-5-chloro-2——methoxybenzoate 7 g h。7 g (Ki = 0.26 + / - 0.06海里)抑制的松弛剂作用5大鼠食道肌肉pA2值为8.6。酯的优点比较函数证明了几个这样的活性化合物在5-HT4受体与相应amidic衍生品。这种差异不明显,基本一半是sterically受限quinuclidine和托烷半个。结构分析的7 g进行通过确定他们的x射线晶体结构和分子建模(SYBYL)。 A relatively limited number of minimum energy conformers was found for both compounds. They were characterized by the cis folded conformation of the ethyl chain and by the orientation of the lone pair of the nitrogen atom pointing out of the molecule as seen in conformationally-constrained benzamides such as zacopride and renzapride. A hypothetical model for the 5-HT4 receptor with two sites for the binding of agonist and antagonist molecules was proposed.