新型吡啶并[3,2-e][1,2,4]三唑并[1,5-c]嘧啶衍生物的合成：有效的和选择性的腺苷 A3 受体拮抗剂。
Synthesis of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives: potent and selective adenosine A3 receptor antagonists.
机构信息
Fluoroorganic Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, Andhra Pradesh, India.
出版信息
Arch Pharm (Weinheim). 2013 Oct;346(10):699-707. doi: 10.1002/ardp.201300003. Epub 2013 Aug 30.
A series of novel pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 5 was prepared from 2-amino-3-cyano-4-trifluoromethyl-6-phenylpyridine 1 in two steps via formation of iminoether 3 followed by reaction with different aroylhydrazides 4. Representative products 5 were evaluated for their affinity towards all four subtypes of human adenosine receptors. Compounds 2-(3-fluorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5b), 2-(furan-2-yl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5d), and 2-(furan-2-yl)-5-methyl-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (5j) showed high affinity for the A3 receptors, with Ki values of 8.1, 10.4, and 12.1 nM, respectively, and were >1000-fold selective versus all other adenosine receptor subtypes.
一系列新型吡啶并[3,2-e][1,2,4]三唑并[1,5-c]嘧啶衍生物 5 是由 2-氨基-3-氰基-4-三氟甲基-6-苯基吡啶 1 通过形成亚氨基醚 3 然后与不同的芳酰肼 4 反应两步合成的。代表性产物 5 被评估了对所有四种人类腺苷受体亚型的亲和力。化合物 2-(3-氟苯基)-8-苯基-10-(三氟甲基)吡啶并[3,2-e][1,2,4]三唑并[1,5-c]嘧啶（5b）、2-(呋喃-2-基)-8-苯基-10-(三氟甲基)吡啶并[3,2-e][1,2,4]三唑并[1,5-c]嘧啶（5d）和 2-(呋喃-2-基)-5-甲基-8-苯基-10-(三氟甲基)吡啶并[3,2-e][1,2,4]三唑并[1,5-c]嘧啶（5j）对 A3 受体表现出高亲和力，Ki 值分别为 8.1、10.4 和 12.1 nM，对所有其他腺苷受体亚型的选择性 >1000 倍。
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