Organocatalyzed Domino Synthesis of New Thiazole-Based Decahydroacridine-1,8-diones and Dihydropyrido[2,3-d : 6,5-d']- dipyrimidines in Water as Antimicrobial Agents.

Organopromoter, 2-aminoethanesulfonic acid was used to catalyze the synthesis of a series of structurally intriguing new hybrids thiazolyl acridine-1,8(2H,5H)-diones and dihydropyrido[2,3-d : 6,5-d']dipyrimidine-2,4,6,8(1H,3H,5H,7H)-tetraones for the first time. 2-Aminoethanesulfonic acid is a biobased organopromoter, used to generate four new bonds for the synthesis of new coupled thiazole-based decahydroacridine-1,8-diones. Superior green credentials, operational simplicity, easy work-up and recyclability of the catalyst are the key strengths of this method. The broad substrate scope, mild reaction conditions, short reaction time, cost effectiveness, high atom economy and good to excellent yields make the present method a distinct improvement over existing methods. Spectral (IR, 1 H-NMR,13 C-NMR, Mass) data and elemental analyses confirmed the structures of the titled products. A series of thiazolyl acridine-1,8(2H,5H)-diones and dihydropyrido[2,3-d : 6,5-d']dipyrimidine-2,4,6,8(1H,3H,5H,7H)-tetraones were screened for their antimicrobial activity against four bacterial and three fungal strains.

Synthesis and antitubercular activity of new 1,3,4-oxadiazoles bearing pyridyl and thiazolyl scaffolds.

In search of more potent and safe new antitubercular agents, here new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o), have been designed and synthesized using thionicotinamide as a starting, following novel multistep synthetic route. An intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic acids/nicotinic acids (5a-o) in the presence of silica supported POCl3 yielded better to excellent yields of the title compounds. All the synthesized compounds (6a-o) and intermediate acid hydrazide (4) have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG. Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at concentrations less than 3µg/mL. These compounds have shown low cytotoxicity (CC50: >100µg/mL) towards four human cancer cell lines. Molecular docking study has also been performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the binding modes of these molecules and recorded good binding affinity. The ADME properties the title products have also been analyzed.

Synthesis of new thiazolylmethoxyphenyl pyrimidines and antihyperglycemic evaluation of the pyrimidines, analogues isoxazolines and pyrazolines.

New thiazolylmethoxyphenyl pyrimidines (7a-g) have been conveniently synthesized with better yields by cyclocondensing 3-(4-((2-phenylthiazol-4-yl)methoxy)phenyl)-1-(4-substituted phenyl)prop-2-en-1-ones (4a-g) with thiourea in aqueous emulsion of tetradecyltrimethylammonium bromide (TTAB) at 80 °C. Antihyperglycemic activity of the new thiazolylmethoxyphenyl pyrimidines (7a-d), thiazolylmethoxyphenyl pyrazolines (5a-d) and thiazolylmethoxyphenyl isoxazolines (6a-d) has been evaluated in sucrose loaded rat model. Among these compounds; 5a, 5c, 6b, 7c and 7d have displayed noticeable antihyperglycemic activity. Pyrimidines and pyrazolines have displayed better antihyperglycemic activity than the analogues isoxazolines.

Synthesis and antihyperglycemic evaluation of new 2-hydrazolyl-4-thiazolidinone-5-carboxylic acids having pyrazolyl pharmacophores.

In the search of new antihyperglycemic agents and following rational approach of drug designing here new 2-hydrazolyl-4-thiazolidinone-5-carboxylic acids (4a-g) with pyrazolyl pharmacophore have been synthesized via thia Michael addition reaction of 1-((3-(4-substituted phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)thiosemicarbazides (3a-g) with maleic anhydride. The required precursors, (3a-g) were obtained by condensing known 3-(4-substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehydes (1a-g) with thiosemicarbazide in ethanol. The newly synthesized compounds (4a-g) have been evaluated for the antihyperglycemic activity in sucrose loaded rat model and among these compounds 4d, 4f and 4g have displayed significant antihyperglycemic activity.