Microwave assisted synthesis and QSAR study of novel NSAID acetaminophen conjugates with amino acid linkersElectronic supplementary information (ESI) available: Copy of 1H NMR, 13C NMR, HRMS/elemental analysis of all the compounds. HPLC spectra of compound 6b and 6f. Graphs of anti-inflammatory studies. See DOI: 10.1039/c4ob01281j

Novel, non-steroidal anti-inflammatory drug (NSAID), acetaminophen conjugates 6a-l with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates ( 6d , 6e , 6h , and 6k ) exhibit more potent anti-inflammatory activity than their parent drugs, (b) the potent bis-conjugates show no visible stomach lesions in contrast to parent drugs which are highly ulcerogenic, and (c) that the potent bio-active compounds have no mortality rates or toxic symptoms at 5 fold the applied anti-inflammatory dosage. A statistically significant QSAR model describing the anti-inflammatory properties of 6a-l ( N = 15, n = 3, R 2 = 0.891, R 2 cvOO = 0.770, R 2 cvMO = 0.796, F = 29.904, s 2 = 0.011) was obtained employing CODESSA-Pro that validated the observed bio-activity. Twelve novel conjugates of NSAID linked by amino acid units to acetaminophen synthesized under microwave irradiation as potential anti-inflammatory agents.