New bithiazolyl hydrazones: Novel synthesis, characterization and antitubercular evaluation.

New bithiazolyl hydrazones (6a-l) have been first time synthesized by carrying novel one pot cyclocondensation of 5-acyl thiazoles (1a-b), thiosemicarbazide (2) and substituted phenacyl chlorides (4a-f) in freshly prepared ionic liquid, diisopropyl ethyl ammonium acetate (DIPEAc) at room temperature. The newly synthesized compounds have been evaluated for their antitubercular activity and the compounds 3b, 6a, 6b, 6d, 6e, 6f, 6g, and 6l have displayed noticeable antitubercular activity compared to Rifampicin with tolerable cytotoxicity. All these compounds were also screened for their antibacterial activity and found that, compounds 6j and 6k have exhibited a very good antibacterial activity. Molecular docking study has shown better harmony with the evaluation trend shown by these compounds under in vitro antitubercular screening.

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.

Synthesis and antihyperglycemic evaluation of new 2,4-thiazolidinediones having biodynamic aryl sulfonylurea moieties.

New 2,4-thiazolidinediones with aryl sulfonylurea moieties have been synthesized by condensing various substituted sulfonamides and 5-(isocyanatomethyl) thiazolidino-2,4-dione. The isocyanomethyl thiazolidinedione was obtained by using the Curtius rearrangement, starting from known 2,4-dioxo-5-thiazolidineacetic acid. The newly synthesized compounds have been evaluated for the antihyperglycemic activity in normal rats model and among these compounds showed significant antihyperglycemic activity in sucrose loaded rat model.

An alternative synthetic route for an antidiabetic drug, rosiglitazone.

A convenient and scalable four-step novel route has been developed for the synthesis of rosiglitazone (8), an antidiabetic drug. This multistep route requires 4-fluoro benzaldehyde (4), 2,4-thiazolidinedione (6) and 2-chloro pyridine (1) as key reactants and gives overall better yield of rosiglitazone. In addition, some steps have been accelerated, which leads to an overall time saving of 10h.