Katsushima T, Nieves L, Wells J N
Department of Pharmacology, Vanderbilt University, School of Medicine, Nashville 37232.
J Med Chem. 1990 Jul;33(7):1906-10. doi: 10.1021/jm00169a012.
8-Substituted xanthines currently represent the most potent class of adenosine-receptor antagonists. A series of 8-substituted 1,3-dipropylxanthines was prepared and their potency as antagonists of A1 and A2 adenosine receptors of human platelets and rat adipocytes, respectively, were determined. No agents studied were as potent as 8-cyclopentyl-1,3-dipropylxanthine as antagonists of the A1 adenosine receptor, but 8-(2-methylcyclopropyl)-1,3-dipropylxanthine was at least 1000-fold more potent as an antagonist of A1 than of A2 adenosine receptors. While most substitutions on the 8-cycloalkyl moiety caused decreased potency to inhibit both A1 and A2 adenosine receptors, 8-[trans-4-(acetamidomethyl)cyclohexyl]-1,3-dipropylxanthine was nearly equipotent as an antagonist of the two receptors and appeared to be the most potent antagonist of A2 adenosine receptors reported to date.
8-取代黄嘌呤目前是最有效的一类腺苷受体拮抗剂。制备了一系列8-取代的1,3-二丙基黄嘌呤，并分别测定了它们作为人血小板和大鼠脂肪细胞A1和A2腺苷受体拮抗剂的效力。所研究的试剂中没有一种作为A1腺苷受体拮抗剂的效力能与8-环戊基-1,3-二丙基黄嘌呤相媲美，但8-(2-甲基环丙基)-1,3-二丙基黄嘌呤作为A1腺苷受体拮抗剂的效力至少比作为A2腺苷受体拮抗剂的效力强1000倍。虽然8-环烷基部分的大多数取代导致抑制A1和A2腺苷受体的效力降低，但8-[反式-4-(乙酰氨基甲基)环己基]-1,3-二丙基黄嘌呤作为这两种受体的拮抗剂效力几乎相当，并且似乎是迄今为止报道的最有效的A2腺苷受体拮抗剂。
