A1 adenosine receptor antagonists as ligands for positron emission tomography (PET) and single-photon emission tomography (SPET).
A1 adenosine receptor antagonists as ligands for positron emission tomography (PET) and single-photon emission tomography (SPET).
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A1 腺苷受体拮抗剂作为正电子发射断层扫描 (PET) 和单光子发射断层扫描 (SPET) 的配体。
DOI：
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发表时间：
1998
影响因子：
7.3
通讯作者：
R. Olsson
中科院分区：
文献类型：
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作者：
M. Holschbach;T. Fein;C. Krummeich;R. Lewis;W. Wutz;U. Schwabe;D. Unterlugauer;R. Olsson
8-环戊基-1,3-二丙基黄嘌呤（CPX）对A1腺苷受体（A1AR）的高亲和力为开发适合正电子发射断层扫描（PET）和单光子发射断层扫描（SPET）的放射配体提供了良好的先导。该研究验证了这样一种假设，即在合成含有碳-11、氟-18或放射性碘的CPX类似物时进行的各种化学修饰不会改变对A1AR的亲和力。本报告描述了在N-1 （13a-d）或N-3 （8a-d）上分别具有甲基、2-甲氧基乙基、2-氟丙基或3-氟丙基取代基或在N-3 （8f）上具有(E)-3-碘丙基-2-en-1基取代基的未标记CPX类似物的合成和放射性配基结合测定。化合物8d、f和13b、d可拮抗[3H]CPX与大鼠脑A1AR的结合，其亲和性与CPX相似；化合物8c的效力是CPX的两倍。类似物8a、b和13a的拮抗作用均低于CPX，但其Ki均为0.5 nM或bb0 nM。试图碘化CPX的8-（4-羟基苯基）类似物失败了，可能是因为黄嘌呤取代基强烈地使苯酚失活，导致亲电碘化。综上所述，CPX的一些丙基修饰需要产生用于PET和SPET成像的配体，以保持或增强对A1AR的亲和力。
The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A1 adenosine receptor (A1AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-11, fluorine-18, or radioiodine will not alter affinity for the A1AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [3H]CPX to the A1AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the Ki of antagonism was > or = 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A1AR.