Elzein Elfatih, Kalla Rao, Li Xiaofen, Perry Thao, Parkhill Eric, Palle Venkata, Varkhedkar Vaibahv, Gimbel Art, Zeng Dewan, Lustig David, Leung Kwan, Zablocki Jeff
Department of Bioorganic Chemistry, CV Therapeutics Inc., 3172 Porter Drive, Palo Alto, CA 94304, USA.
Bioorg Med Chem Lett. 2006 Jan 15;16(2):302-6. doi: 10.1016/j.bmcl.2005.10.002. Epub 2005 Nov 4.
A series of new 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as A(2B)-AdoR antagonists have been synthesized and evaluated for their binding affinities for the A(2B), A(1), A(2A), and A(3)-AdoRs. 8-(1-((3-phenyl-1,2,4-oxadiazol-5-yl)methyl)-1H-pyrazol-4-yl)-1,3-dipropyl-1H-purine-2,6(3H,7H)-dione (4) displayed high affinity (K(i)=1 nM) and selectivity for the A(2B)-AdoR versus A(1), A(2A), and A(3)-AdoRs (A(1)/A(2B), A(2A)/A(2B), and A(3)/A(2B) selectivity ratios of 370, 1100, and 480, respectively). The synthesis and SAR of this novel class of compounds are presented herein.
已合成了一系列新型的1,3 - 二丙基 - 8 -（1 - 杂芳基甲基 - 1H - 吡唑 - 4 - 基） - 黄嘌呤衍生物作为A(2B) - 腺苷受体拮抗剂，并评估了它们对A(2B)、A(1)、A(2A)和A(3) - 腺苷受体的结合亲和力。8 -（1 -（（3 - 苯基 - 1,2,4 - 恶二唑 - 5 - 基）甲基） - 1H - 吡唑 - 4 - 基） - 1,3 - 二丙基 - 1H - 嘌呤 - 2,6(3H,7H) - 二酮（4）对A(2B) - 腺苷受体相对于A(1)、A(2A)和A(3) - 腺苷受体表现出高亲和力（K(i)=1 nM）和选择性（A(1)/A(2B)、A(2A)/A(2B)和A(3)/A(2B)的选择性比率分别为370、1100和480）。本文介绍了这类新型化合物的合成及构效关系。
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