title: Synthesis and evaluation of novel 2-butyl-4-chloro-1-methylimidazole embedded chalcones and pyrazoles as angiotensin converting enzyme (ACE) inhibitors.
abstract: A series of novel 2-butyl-4-chloro-1-methylimidazole embedded aryl and heteroaryl derived chalcones and pyrazoles were synthesized and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. The condensation of 2-butyl-4-chloro-1-methylimidazole-5-carboxaldehyde with various aryl and heteroaryl methyl ketones in the presence of 10% aqueous NaOH in methanol proceeded efficiently to give the respective chalcones in very good yields. Further, the reaction of chalcones with hydrazine hydrate in acetic acid gave substituted pyrazole analogues. Screening all 36 new compounds using ACE inhibition assay, resulted chalcones with better ACE inhibitory activity compared to the respective pyrazole analogues. Among the chalcones 4a-r, three compounds, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(5-chlorothiophen-2-yl)prop-2-enone 4i, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(1H-pyrrol-2-yl)prop-2-enone 4l, (E)-3-(2-butyl-4-chloro-1-methyl-1H-imidazol-5-yl)-1-(dibenzo[b,d] thiophen-2-yl)prop-2-enone 4q were resulted as most active ACE inhibitors with IC(50) of 3.60 μM, 2.24 μM, and 2.68 μM, respectively.
authors.affiliation: Organic Chemistry Division-II, Indian Institute of Chemical Technology, Hyderabad 500 607, India. Kantevari@yahoo.com
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kantevari
authors.forename: Dinesh
authors.initials: D
authors.lastname: Addla
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Bagul
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Sridhar
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047188:Chalcones / Q000138:chemical synthesis; D004353:Drug Evaluation, Preclinical; D006834:Hydrazines / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis; D013329:Structure-Activity Relationship
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D047188:Chalcones; D006834:Hydrazines; D007093:Imidazoles; D011720:Pyrazoles; C029424:hydrazine; C018100:1-methylimidazole