Synthesis of hybrid analogues of caffeine and eudistomin D and its affinity for adenosine receptors
Synthesis of hybrid analogues of caffeine and eudistomin D and its affinity for adenosine receptors
复制标题
咖啡因和eudistomin D混合类似物的合成及其对腺苷受体的亲和力
DOI：
10.1016/j.bmc.2009.05.036
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
J.
中科院分区：
文献类型：
--
作者：
Ishiyama;H.; Nakajima;H.; Nakata;H.; Kobayashi;J.
本文合成了2种杂化分子（1和2）的尿嘧啶环上的4个双n- n-丙基类似物（3-6），并检测了它们对腺苷受体A1、A2A和a3的亲和力和选择性。所有化合物（3-6）作为腺苷受体配体的效力均优于咖啡因。1和2中尿嘧啶环的双n- n-丙基化（分别为3和4）导致对a1和a2a腺苷受体具有更高的亲和力。此外，化合物(5)在化合物3的C-7位上含有一个正丙基，在吡啶环的β-位上含有一个氮（β-N型），显著增强了对腺苷受体A3亚型的亲和力，而化合物(6)在化合物4的C-5位上含有一个正丙基，在吡啶环的δ-位上含有一个氮（δ-N型），降低了对所有腺苷受体A1、A2A和A3的亲和力。在所检测的化合物（1 ~ 6）中，化合物5对腺苷受体a3亚型的亲和力最强（Kivalue, 0.00382μM）。
Four bis-N-n-propyl analogues (3–6) in the uracil ring of two hybrid molecules (1 and 2) of caffeine and eudistomin D, a β-carboline alkaloid from a marine tunicate, were synthesized, and their affinity and selectivity for adenosine receptors A1, A2A, and A3were examined. All the compounds (3–6) showed better potency as adenosine receptor ligands than caffeine. Bis-N-n-propylation (3 and 4, respectively) of the uracil ring in 1 and 2 resulted in higher affinity for A1and A2Aadenosine receptors. Furthermore, it was found that a compound (5) possessing a n-propyloxy group at C-7 in compound 3 with a nitrogen at the β-position of the pyridine ring (β-N type) enhanced remarkably affinity for adenosine receptor A3subtype, while n-propyloxy substitution (compound 6) at C-5 in compound 4 with a nitrogen at the δ-position of the pyridine ring (δ-N type) reduced affinity for all the adenosine receptor, A1, A2A, and A3. Among all the compounds (1–6) examined, compound 5 showed the most potent affinity for adenosine receptor A3subtype (Kivalue, 0.00382μM).