取代吡唑类化合物作为新型人多巴胺D4受体选择性配体。

Substituted pyrazoles as novel selective ligands for the human dopamine D4 receptor.

作者信息

Bourrain S, Collins I, Neduvelil J G, Rowley M, Leeson P D, Patel S, Patel S, Emms F, Marwood R, Chapman K L, Fletcher A E, Showell G A

机构信息

Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.

出版信息

Bioorg Med Chem. 1998 Oct;6(10):1731-43. doi: 10.1016/s0968-0896(98)00134-5.

DOI:10.1016/s0968-0896(98)00134-5

PMID:9839003

Abstract

Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D4 receptor. Compounds in series I (exemplified by 8k) have a phenyl ring joined to the 4-position of the pyrazole while those in series II (exemplified by 15j) have a 5-phenyl ring linked by a saturated chain to the 4-position of the pyrazole. Both series supplied compounds with excellent affinity for the human D4 and good selectivity over other dopamine receptors. Excellent selectivity over calcium, sodium, and potassium ion channels was also achieved.

摘要

已经合成了两个新型的3-(杂环甲基)吡唑系列，并将其作为人类多巴胺D4受体的配体进行了评估。系列I中的化合物（以8k为例）在吡唑的4位连接有一个苯环，而系列II中的化合物（以15j为例）有一个5-苯环通过饱和链连接到吡唑的4位。两个系列都提供了对人类D4具有优异亲和力且对其他多巴胺受体具有良好选择性的化合物。还实现了对钙、钠和钾离子通道的优异选择性。