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Abstract

ISO-STERIC REPLACEMENT OF THIAZOLIDIENE DIONE TO IMIDAZOLINE DIONE (HYDANTOIN) AS A NOVEL SCAFFOLD: SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF PTP1B INHIBITORS.

Ankit C. Borisa*, Hardik G. Bhatt, Dinesh Thakkar, Sneha Trivedi.

ABSTRACT

Diabetes affects 12% of the total population in world. So it is very important to treat this fatal disease. There are many marketed preparation is available to treat diabetes but not a single medicine have the ability to cure it. A thirst in research area is more and more increased now a day. Novel pathways and targets are identified in current time that may be kill this dragon named diabetes. Inhibition of a novel target PTP1B is chosen for attack on diabetes. PTP1B inhibition reported as negative regulator of insulin signaling pathway which increased the insulin sensitivity on insulin receptor. The numerous scaffold are reported and still so much research task going on for PTP1B inhibition. We choose Hydantoin scaffold as novel inhibition of PTP1B and design molecule that binds with this enzyme and inhibit it. A series of substituted 2-[4-[(2,5-dioxo imidazolidin-4- ylidene) methyl] Aryloxy] -N-arylacetamide is decided to synthesized. The inhibition of PTP1B is in vitro tested over PTP1B enzymatic kit. Among all the tested compounds, two compound were found most potent activity 90.59% & 97.56 % inhibition respecively (N-(4-bromophenyl)-2- [4-[(2,5- dioxoimidazolidin-4-ylidene)methyl] phenoxy]acetamides) and (2-[[2-[4-[(2,5- dioxoimidazolidin-4-ylidene)methyl] phenoxy] acetyl]amino]benzoic acid) with compared to standard drug suramin.

Keywords: Diabetes, PTP1B, Hydantoin, imidazoline 2-4 dione.


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