Synthesis, receptor potency, and selectivity of halogenated diphenylpiperidines as serotonin 5-HT2A ligands for PET or SPECT brain imaging.
Synthesis, receptor potency, and selectivity of halogenated diphenylpiperidines as serotonin 5-HT2A ligands for PET or SPECT brain imaging.
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作为用于 PET 或 SPECT 脑成像的血清素 5-HT2A 配体的卤化二苯基哌啶的合成、受体效力和选择性。
DOI：
10.1021/jm0200411
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发表时间：
2002
影响因子：
7.3
通讯作者：
Baldwin,RonaldM
中科院分区：
文献类型：
--
作者：
Fu,Xing;Tan,Ping-Zhong;Kula,NoraS;Baldessarini,Ross;Tamagnan,Gilles;Innis,RobertB;Baldwin,RonaldM
合成了一系列4‘-取代苯基-4-哌啶甲醇和苯甲酰基-4-哌啶类化合物作为潜在的新型5-羟色胺5-羟色胺受体配体，可用于活体脑成像。4-取代苯甲酰基-4-哌啶与碘或氟取代的苯基烷基卤化物发生烷基化反应，然后用硼氢化钠还原得到化合物。用5-羟色胺5-羟色胺受体的体外放射受体亲和力测定新化合物的效价。进一步评估了有效化合物对5-羟色胺-2A与2C、6和7以及多巴胺D2和肾上腺素能α1和α2受体的选择性。新化合物(4-fluorophenyl)-(1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl])methanol特别有希望具有高的5-HT2活性(Ki=1.63nM)和比其他类型的5-羟色胺受体高300倍的选择性。
A series of 4‘-substituted phenyl-4-piperidinylmethanol and benzoyl-4-piperidine derivatives was synthesized as potential novel serotonin 5-HT2Areceptor ligands that can be radiolabeled for in vivo brain imaging. Compounds were prepared by alkylation of 4-substituted benzoyl-4-piperidine with an iodo- or fluoro-substituted phenylalkyl halide followed by reduction with sodium borohydride. Potency of novel compounds was determined by in vitro radioreceptor affinity assays selective for serotonin 5-HT2Areceptors. Potent compounds were further evaluated for selectivity at serotonin-2A versus 2C, 6, and 7, as well as dopamine D2and adrenergic α1and α2receptors. The novel compound (4-fluorophenyl)-(1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl])methanol was particularly promising with high 5-HT2Apotency (Ki= 1.63 nM) and >300-fold selectivity over other 5-HT receptor types.