Journal of Medicinal Chemistry p. 2101 - 2108 (1990)
Update date:2022-08-05
Topics:
Turconi, Marco
Nicola, Massimo
Quintero, Myrna Gil
Maiocchi, Luciano
Micheletti, Rosella
et al.
A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid esters and amides containing a basic azacyclo- or azabicycloalkyl moiety has been synthesized and evaluated for 5-HT3 antagonistic activity in a radioligand binding assay (<3>ICS 205930) and in the 5-HT-induced von Bezold-Jarisch reflex in the rat.It was found that endosubstituted azabicycloalkyl derivatives (e.g. 7a, 12a, 12b) were much more active than the corresponding exo analogues (e. g. 7b, 12h, 12i) or azacycloalkyl compounds.Amidic derivatives 12a, 12b, 12c, 12e, 13b, and 13c proved to be about 10 tim es more active than the corresponding ester derivatives 7a, 11a, 7d, 8a, and 8b.In particular, compound 12a (DA 6215) showed a Ki=3.8 nM in the binding test and an ED50=1 nM/kg iv in the von Bezold-Jarisch reflex assay, an activity comparable to that of the reference compound 2 (ICS 205930, Ki=2 nM, ED50=2.1 nM/kg).IR spectroscopy studies in the solid state and in CHCl3 solution revealed the existence of an intramolecular hydrogen bond in 13b, taken as a model compound for this class of substances.A molecular modeling study showed that 12a, in its internal hydrogen-bound conformation, well matches a recently proposed pharmacophoric model for 5-HT3 antagonist activity.
View MoreShanghai Synmedia Chemical Co., Ltd
Contact:+86-21-38681880
Address:6th Floor, 11A Building, No.528 Ruiqing Road, Heqing town, Pudong new district, Shanghai China
Qingzhou Baibang import and export co.,Ltd
Contact:+86-536-3265899
Address:No.338, Tuoshan Road
Sichuan Ziren Pharmaceutical Co., Ltd
Contact:
Address:West 3 Section, Shenzhen Road, Guanghan
Contact:021-36356756
Address:Room601,Building No.14,280 Yangcheng Road,Shanghai
website:http://www.maisonchem.com.cn
Contact:0086-311-83833777
Address:Leitou industrial district, xinji, shijiazhuang city, hebei province,
Doi:10.1080/00397911.2019.1614627
(2019)Doi:10.1021/ja102753d
(2010)Doi:10.1021/jm301859s
(2013)Doi:10.1002/cmdc.201000044
(2010)Doi:10.1021/ol1011532
(2010)Doi:10.1016/j.tetlet.2010.04.045
(2010)