Steric and electronic requirements for muscarinic receptor-stimulated phosphoinositide turnover in the CNS in a series of arecoline bioisosteres.
Steric and electronic requirements for muscarinic receptor-stimulated phosphoinositide turnover in the CNS in a series of arecoline bioisosteres.
复制标题
在一系列槟榔碱生物等排体中，中枢神经系统中毒蕈碱受体刺激的磷酸肌醇周转的空间和电子需求。
DOI：
10.1016/0006-291x(92)90456-u
复制
发表时间：
1992
影响因子：
3.1
通讯作者：
Hoss,W
中科院分区：
文献类型：
--
作者：
Ngur,D;Roknich,S;Mitch,CH;Quimby,SJ;Ward,JS;Merritt,L;Sauerberg,P;MesserJr,WS;Hoss,W
A series of arecoline derivatives was utilized to assess steric and electronic effects important for activating muscarinic receptors in the CNS. Arecoline derivatives in which the methyl ester moiety was replaced by hexyloxy-1, 2, 5-oxadiazole (2b), hexyloxythiophene (3b) or hexyloxypyrazine (4b) were compared with the hexyloxy-1, 2, 5-thiadiazole compound (1b)(Hexyloxy-TZTP), known from previous work to be active as an M 1 M 3 partial agonist. MNDO calculations showed that the NS bonds of the alkoxythiadiazole ring were highly polarized with the ability to form H-bonds to the N's. On the other hand, the smaller oxadiazole had lower polarities in the NO bonds and reduced ability to form H-bonds, the thiophene was of comparable size to the thiadiazole and had large CS bond polarities without the H-bond capability and the pyrazine had limited ability to form H-bonds. The compounds were compared with respect to their abilities to stimulate phosphoinositide (PI) turnover in the hippocampus of the rat brain. 1b was more active than 2b–4b for stimulating the PI turnover response. The data suggest that the ability to form H-bonds is an important factor for the ability of 1 to stimulate M 1 muscarinic receptors in the CNS.
