Antiinflammatory Evaluation and Docking Studies of Some New Thienopyrimidines

Abstract

A series of some new 6-substituted-2,3,4-trihydropyrimido [1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines (1-6) have been evaluated in silico (docking studies) to recognize their hypothetical binding motif with the cyclooxygenase isoenzyme (COX-2) employing GLIDE software (Schrodinger Inc.) and in vivo (rat paw edema) for their antiinflammatory activities. The compound 6 with pyridyl substitution at the 6 th position of the thienopyrimidine moiety was found to form significant H-bonding interaction with crucial amino acid residue Arg 120 at a distance of 3 Å and exhibited good antiinflammatory activity [around 87 % of the standard: indomethacin]. The binding mode of the thienopyrimidines compounds have been proposed based on the docking studies. Further, the predicted ADME properties of all the tested compounds were found to be in the ranges as predicted by QikProp for 95 % of known oral drugs and also satisfy the Lipinski's rule of five.

Small Molecules Inhibit Extranuclear Signaling by Estrogen: A Promising Strategy to Halt Breast Cancer Progression and Metastasis

“…From the results, the redocked binding pose of the native ligand was correctly reproduced within the root mean square tolerance of 2 Å. This distance is an indication of an appropriate reproducibility for a docking experiment [36,37]. This reproducibility of the redocked native ligand was similar to the poses of the docking control reported by Hocker et al (2013) [38].…”

Molecular Basis of Binding Interactions of NSAIDs and Computer-Aided Drug Design Approaches in the Pursuit of the Development of Cyclooxygenase-2 (COX-2) Selective Inhibitors

“…Several atempts were made to extensively manipulate the ring system that is fused with the cis-stilbene system to include every possible heterocyclic ring of varying sizes as well as by altering the scafolds of classical NSAIDs to convert them into COX-2 selective inhibitors, but none could successfully reach the market. Recently, a series of thiazole derivatives [21], cycloalkyl/aryl-3,4,5-trimethylgallates [22], thienopyrimidine derivatives [23], 3-alkoxy-4-methanesulfonamido acetophenone derivatives [24] and 8/10-triluoromethyl-substituted-imidazo[1,2-c]quinazolines [25], have been designed, synthesised and reported from our research group in search of compounds with novel scafold as potent anti-inlammatory agents.…”

Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives

“…In persistence of our interest in pharmacologically active heterocyclic compounds [40][41][42][43][44][45][46][47][48], polymorphism studies [49][50][51][52], and the discovery of anti-inflammatory agents [53][54][55][56][57][58][59], in the present investigation, we synthesized a range of 7-methoxy indolizine derivatives as indomethacin analogues (Figure 1 and Scheme 1) to evaluate their potential as antiinflammatory agents. The title compounds (5a-e) were evaluated for their pharmacological activity against the COX-2 enzyme in order to study the influence of ethyl ester at the 1and 2-positions, ethyl at the 2-position, and the diverse substituent on the benzoyl ring at the 3-positions of the indolizine core on the biological action.…”