Synthesis and Urease Inhibition Studies of Barbituric and Thiobarbituric Acid Derived Sulphonamides

Abstract

Various novel barbituric and thiobarbituric acid derived sulphonamides were synthesized in excellent yield via three components single pot reaction; and these were screened for in vitro urease inhibition studies against jack bean urease. The compounds 1‐7 were found to exhibit a low to moderate activity whereas compounds 8‐14 showed a significant activity (88.3‐99.9% inhibition determined at 500 μM concentration). Structures of the synthesized compounds were confirmed by 1H‐NMR, 13C‐NMR, mass spectrometry and elemental analysis data.

Design, Synthesis, in vitro Antiproliferative Activity, Binding Modeling of 1,2,4,-Triazoles as New Anti-Breast Cancer Agents

“…In contrast to antibacterial agent, the antiviral drug should have (X δ--Y δ-) pharmacophore site with respect of some architectural parameters (dihedral angle = 0-10 degree and distance d x-y = 3-3.5 Å). [33][34][35][36][37][38][39] This can be applied for all compounds described here ( Figure 5). …”

“…Molecular Polar Surface Area PSA is calculated as a sum of fragment contributions. [33][34][35][36][37][38][39] O-, N-and Scentered polar fragments are considered. PSA has been shown to be a very good descriptor characterizing drug absorption, including intestinal absorption, bioavailability, Caco-2 permeability and blood-brain barrier penetration.…”

“…Lipophilicity (cLogP value) and polar surface area (TPSA) values are two important properties for the prediction of oral bioavailability of drug molecules. [33][34][35][36][37][38][39] Therefore cLogP and TPSA values for compounds (1-8) were calculated using Molinspiration software programs and compared with the values obtained for standard drugs Docetaxel and Tamoxifen. For majority of the compounds, with some exceptions (5 and 6), the calculated cLogP values were around 2.15-4.65 (< 5), which is the upper limit for the drugs to be able to penetrate through bio-membranes according to Lipinski's rule.…”

New barbiturates and thiobarbiturates as potential enzyme inhibitors

“…Furthermore, some are used for the treatment of psychiatric disorders such as anxiety and epilepsy by posing effects on motor and sensory functions 5,6 and are also reported as bactericidal agent 3,4,7 . Previously we have reported and identified various pharmacophores responsible for potent activity of barbiturate/thiobarbiturate nucleus via molecular modeling studies [8][9][10][11] . It is evident that the imide or b-amino a, b-unsaturated amide functionality is the basic structural moiety in these compounds which has multidimensional array of interaction sites resulting in either potential urease inhibitors (PUI), potential antibacterial (PAB), antifungal Inhibitors (PAF) and potential kinase inhibitors (PKI; Figure 1).…”

Synthesis and biological evaluation of novel series of aminopyrimidine derivatives as urease inhibitors and antimicrobial agents

“…Akhtar et al have synthesized 3-substituted-4-amino-5-thioxo-1H-4H-1,2,4-triazoles derivatives showing their urease inhibition activity 12 . Rauf et al have reported the synthesis and urease inhibition activity of barbituric and thiobarbituric acid derivatives 13 . More recently, Khan et al also reported arylidene barbiturates as urease inhibitors 14 .…”