Dihydropyrimidones: As novel class of β-glucuronidase inhibitors

Dihydropyrimidones 1-37 were synthesized via a 'one-pot' three component reaction according to well-known Biginelli reaction by utilizing Cu(NO3)(2)center dot 3H(2)O as catalyst, and screened for their in vitro beta-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC50 = 28.16 +/- .056 mu M), 9 (IC50 = 18.16 +/- 0.41 mu M), 10 (IC50 = 22.14 +/- 0.43 mu M), 13 (IC50 = 34.16 +/- 0.65 mu M), 14 (IC50 = 17.60 +/- 0.35 mu M), 15 (IC50 = 15.19 +/- 0.30 mu M), 16 (IC50 = 27.16 +/- 0.48 mu M), 17 (IC50 = 48.16 +/- 1.06 mu M), 22 (IC50 = 40.16 +/- 0.85 mu M), 23 (IC50 = 44.16 +/- 0.86 mu M), 24 (IC50 = 47.16 +/- 0.92 mu M), 25 (IC50 = 18.19 +/- 0.34 mu M), 26 (IC50 = 33.14 +/- 0.68 mu M), 27 (IC50 = 44.16 +/- 0.94 mu M), 28 (IC50 = 24.16 +/- 0.50 mu M), 29 (IC50 = 34.24 +/- 0.47 mu M), 31 (IC50 = 14.11 +/- 0.21 mu M) and 32 (IC50 = 9.38 +/- 0.15 mu M) found to be more potent than the standard D-saccharic acid 1,4-lactone (IC50 = 48.4 +/- 1.25 mu M). Molecular docking study was conducted to establish the structure-activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as H-1, C-13 NMR, EIMS and HREI-MS. (C) 2016 Elsevier Ltd. All rights reserved.