Racemic O-methyl O-pheayl thiophosphoric acid 1 has been successfully resolved through its quinine and brucine salts in methanol solution by fractional crystallization. The absolute configurations of the optically act...Racemic O-methyl O-pheayl thiophosphoric acid 1 has been successfully resolved through its quinine and brucine salts in methanol solution by fractional crystallization. The absolute configurations of the optically active 1 have been established as (+)-R-1 and (-)-S-1 by chemical correlation.展开更多
Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the ef- fects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on...Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the ef- fects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on the basis of the asymmetric Sharpless epoxidation. （S）-Iodiconazole was proved to have better antifungal activity than the （R）- isomer. The binding modes of the two isomers with lanosterol 14~z-demethylase were clarified by molecular dock- ing.展开更多
In order to compare the potential selectivity of R-（-）-DM-phencynonate hydrochloride with its racemate （±）-DM- phencynonate hydrochloride on acetylcholine muscarinic receptor subtypes, the five human acetylch...In order to compare the potential selectivity of R-（-）-DM-phencynonate hydrochloride with its racemate （±）-DM- phencynonate hydrochloride on acetylcholine muscarinic receptor subtypes, the five human acetylcholine muscarinic receptor subtypes （M1- M5） （CHO-hml-5R） were cloned and expressed in Chinese hamster ovary （CHO-K1） cell line. The specific mRNAs of the five acetylcholine muscarinic receptor subtypes were detected by the reverse transcription-polymerase chain reaction （RT-PCR） method, demonstrating the definite expression of muscarinic receptor subtype genes （CHO-hml-5R）. The affinity and saturability of different muscarinic receptor subtypes to [^3H] N-methylscopolamine （[^3H]-NMS） were obtained by radioligand binding assay. Equilibrium binding assay revealed that the maximum binding capacity of [^3H]-NMS （Bmax value） to CHO-hml-5R were 40.22±3.23, 24.53±4.11, 29.65±2.65, 25.41±2.46, 32.78±4.81 pmol/mg·protein, respectively. Kd values of [^3H]-NMS to muscarinic receptors M1 to M5 were 0.97±0.22, 1.16±0.14, 0.99±0.06, 0.56±0.08, 1.12±0.06 nM, respectively. R-（-）-DM- phencynonate hydrochloride was found to block the M4 receptor with a much higher potency （pD2 = 7.48） than those displayed on M1 （pD2 = 6.20）, M2 （pD2 = 5.99）, M3 （pD2 = 5.99） and M5 （pD2 = 6.70） subtypes. However, for （±）-DM-phencynonate hydrochloride, no significant subtype receptor selectivity was found. Both （±）-DM- and R-（-）-DM-phencynonate hydrochloride showed allosteric effects on muscarinic receptors, the Hill coefficient （nH） of five receptor subtypes was less than 1, respectively. The results revealed that R-（-）-DM-phencynonate hydrochloride showed selectivity torwards M4 subtype, and there were allosteric effects for both R-（-）-DM-phencynonate hydrochloride and （±）-DM-phencynonate hydrochloride on muscarinic receptors.展开更多
基金This project was supported by National Natural Science Foundation of China
文摘Racemic O-methyl O-pheayl thiophosphoric acid 1 has been successfully resolved through its quinine and brucine salts in methanol solution by fractional crystallization. The absolute configurations of the optically active 1 have been established as (+)-R-1 and (-)-S-1 by chemical correlation.
基金the National Natural Science Foundation of China，Shanghai Municipal Health Bureau
文摘Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the ef- fects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on the basis of the asymmetric Sharpless epoxidation. （S）-Iodiconazole was proved to have better antifungal activity than the （R）- isomer. The binding modes of the two isomers with lanosterol 14~z-demethylase were clarified by molecular dock- ing.
基金National Natural Science Foundation of China (Grant No. 30672445)
文摘In order to compare the potential selectivity of R-（-）-DM-phencynonate hydrochloride with its racemate （±）-DM- phencynonate hydrochloride on acetylcholine muscarinic receptor subtypes, the five human acetylcholine muscarinic receptor subtypes （M1- M5） （CHO-hml-5R） were cloned and expressed in Chinese hamster ovary （CHO-K1） cell line. The specific mRNAs of the five acetylcholine muscarinic receptor subtypes were detected by the reverse transcription-polymerase chain reaction （RT-PCR） method, demonstrating the definite expression of muscarinic receptor subtype genes （CHO-hml-5R）. The affinity and saturability of different muscarinic receptor subtypes to [^3H] N-methylscopolamine （[^3H]-NMS） were obtained by radioligand binding assay. Equilibrium binding assay revealed that the maximum binding capacity of [^3H]-NMS （Bmax value） to CHO-hml-5R were 40.22±3.23, 24.53±4.11, 29.65±2.65, 25.41±2.46, 32.78±4.81 pmol/mg·protein, respectively. Kd values of [^3H]-NMS to muscarinic receptors M1 to M5 were 0.97±0.22, 1.16±0.14, 0.99±0.06, 0.56±0.08, 1.12±0.06 nM, respectively. R-（-）-DM- phencynonate hydrochloride was found to block the M4 receptor with a much higher potency （pD2 = 7.48） than those displayed on M1 （pD2 = 6.20）, M2 （pD2 = 5.99）, M3 （pD2 = 5.99） and M5 （pD2 = 6.70） subtypes. However, for （±）-DM-phencynonate hydrochloride, no significant subtype receptor selectivity was found. Both （±）-DM- and R-（-）-DM-phencynonate hydrochloride showed allosteric effects on muscarinic receptors, the Hill coefficient （nH） of five receptor subtypes was less than 1, respectively. The results revealed that R-（-）-DM-phencynonate hydrochloride showed selectivity torwards M4 subtype, and there were allosteric effects for both R-（-）-DM-phencynonate hydrochloride and （±）-DM-phencynonate hydrochloride on muscarinic receptors.
