Synthesis and Biological Evaluation of Novel Quinolines and Oxepines

Abstract

In the present workpyrimido[5,4-c]quinoline-2,4(1H,3H)-diones (5-24) were synthesized by two step reaction sequence involving Knoevenagel condensation and Doebner Miller reaction. Compounds (5-24) were availed by fusion of Knoevenagel adducts (5benzylidenepyrimidine-2,4,6(1H,3H,5H)-trione and 5-(3-nitrobenzylidene)pyrimidine2,4,6(1H,3H,5H)-trione) (3a-b) with anilines viz. sulfanilamide, 4-amino-N-(thiazol-2yl)benzenesulfonamide, sulfamethazine, sulfaguanidine, sulfamethoxazole, paminobenzoic acid, p-nitroaniline, 3-nitroaniline, 3-hydroxyaniline, p-phenylaniline, 5amino-2-hydroxybenzoic acid, 3-aminoacetophenone, 4-amino-2-hydroxybenzoic acid, 4aminoacetophenone and 4-chloroaniline (4a-o) in an oil bath at 170-265 oC afforded desired compounds in moderate to good yields (55-74%). All the compounds were tediously characterized. The prepared compounds (5-19) were tested for their in vitro antioxidant activity and at all instances they exhibited excellent activity in comparison to control Ascorbic acid. Compounds (20-24) were selectively screened for in vitro antibacterial and antiviral activities as these compounds has active pharmacophores in the structure. The most active compounds were 23, 21 and 22 having MIC 0.5, 1.25 and 1.75 µg respectively against P. vulgaris where ampicillin (MIC 2.25 µg) was employed as positive control. In case K. pneumonia compound 24 was found most active (MIC 0.1 µg) in comparison to control ampicillin (MIC 1.25 µg). In case of antiviral activity of the synthesized compounds (2024), compound (23) has expressed maximum in ovo antiviral potency against all four viruses (AIVH9N2, NDV, IBDV and IBV) with IC50 (0.001 µM). In case of synthesis of oxepines (38, 38´, 43 and 43´), a multi-step strategy (9 steps) is developed starting from 1-indanone anf finally the more polar compound 38 was dyrolysed to compound (40) to avail above mentioned compounds in respectable overall yield (0.39%).