2. Academic Validation
  3. Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening

Discovery of thiazolyl-phthalazinone acetamides as potent glucose uptake activators via high-throughput screening

  • Bioorg Med Chem Lett. 2013 Oct 15;23(20):5740-3. doi: 10.1016/j.bmcl.2013.07.067.
Madhavi Agrawal 1,  Prashant Kharkar,  Sonali Moghe,  Tushar Mahajan,  Vaishali Deka,  Chandni Thakkar,  Amrutha Nair,  Chirag Mehta,  Julie Bose,  Asha Kulkarni-Almeida,  Dilip Bhedi,  Ram A Vishwakarma
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Piramal Enterprises Limited, 1, Nirlon Complex, Goregaon (E), Mumbai, India. Electronic address: madhavi.agrawal@piramal.com.
PMID: 23992862 DOI: 10.1016/j.bmcl.2013.07.067
Abstract

With the aim to discover orally active small molecules that stimulate glucose uptake, high throughput screening of a library of 5000 drug-like compounds was conducted in differentiated skeletal muscle cells in presence of Insulin. N-Substituted phthalazinone acetamide was identified as a potential glucose uptake modulator. Several novel derivatives were synthesized to establish structure activity relationships. Identified lead thiazolyl-phthalazinone acetamide (7114863) increased glucose uptake (EC50 of 0.07±0.02 μM) in differentiated skeletal muscle cells in presence of Insulin. Furthermore, 7114863 was superior to rosiglitazone under similar experimental conditions without inducing PPAR-γ agonist activity thus making it a very interesting scaffold.

Keywords

Glucose uptake activators; Obesity; PPAR-γ; Thiazolyl-phthalazinone acetamides; Type 2 diabetes.

Figures