新型吡咯并嘧啶-6-基苯磺酰胺类化合物：强效A2B腺苷受体拮抗剂。
New pyrrolopyrimidin-6-yl benzenesulfonamides: potent A2B adenosine receptor antagonists.
作者信息
Esteve Cristina, Nueda Arsenio, Díaz José Luis, Beleta Jorge, Cárdenas Alvaro, Lozoya Estrella, Cadavid Maria Isabel, Loza Maria Isabel, Ryder Hamish, Vidal Bernat
机构信息
Medicinal Chemistry Department, Almirall, Treball 2-4, E-08960 St. Just Desvern, Barcelona, Spain.
出版信息
Bioorg Med Chem Lett. 2006 Jul 15;16(14):3642-5. doi: 10.1016/j.bmcl.2006.04.074. Epub 2006 May 11.
A new series of 4-(1,3-dialkyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonamides has been identified as potent A2B adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A2B, A1 and A3 adenosine receptors. 6-(4-{[4-(4-Bromobenzyl)piperazin-1-yl]sulfonyl}phenyl)-1,3-dimethyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (16) showed a high affinity for the A2B adenosine receptor (IC50=1 nM) and selectivity (A1: 183x; A3: 12660x). Synthesis and SAR of this novel class of compounds showing improved absorption properties is presented herein.
一系列新的4-(1,3-二烷基-2,4-二氧代-2,3,4,5-四氢-1H-吡咯并[3,2-d]嘧啶-6-基)苯磺酰胺已被鉴定为强效A2B腺苷受体拮抗剂。已评估了这些产物对人A2B、A1和A3腺苷受体的结合亲和力。6-(4-{[4-(4-溴苄基)哌嗪-1-基]磺酰基}苯基)-1,3-二甲基-1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮(16)对A2B腺苷受体表现出高亲和力(IC50 = 1 nM)和选择性(A1: 183倍；A3: 12660倍)。本文介绍了这类具有改善吸收特性的新型化合物的合成及构效关系。
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