ChemInform Abstract: Synthesis and 5-HT2A Antagonist Activity of Derivatives of the Novel Heterocycles Indolo[3,2-d]pyrrolo[3,2-g]azecine and Benzo[d]pyrrolo[3,2-g]azecine Compared to the Benz[d]indolo[2,3-g]azecine Derivative LE 300

Autor: Ahmed M. Farghaly, Mona M. El-Semary, Sigurd Elz, Sherif A. F. Rostom, Jochen Lehmann, Farid S. G. Soliman
Rok vydání: 2010
Předmět:
Zdroj: ChemInform. 32
ISSN: 1522-2667
0931-7597
DOI: 10.1002/chin.200144167
Popis: An indolo[3,2-d]pyrrolo[3,2-g]azecine and a benzo[d]pyrrolo[3,2-g]azecine analogue of the potent dopamine receptor antagonist LE 300 (7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine) have been prepared in multi-step reactions via C-N bond cleavage of corresponding quatemary N-methylquinolizinium iodides. LE 300, the target compounds and two precursor quinolizines have been tested in vitro for antagonist activity at 5-HT 2A receptors (rat tail artery) and H 1 receptors (guinea-pig ileum), respectively, LE 300 and compound 19 (3,6 dimethyl-4,5,6,7,8,13-hexahydro-3H-benzo[d]pyrrolo[3,2-g]azecine) competitively inhibited 5-HT-induced contractions with similar nanomolar potency (pA 2 = 8.32 and 8.01, respectively) but were less active than the reference antagonist ketanserin (pA 2 = 9.55). Compound 19 displayed moderate H 1 -antihistaminic activity in the guinea-pig ileum assay (pA 2 = 7.37).
Databáze: OpenAIRE
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