Approaches towards the development of chimeric DPP4/ACE inhibitors for treating metabolic syndrome

Jitendra A Sattigeri; Sachin Sethi; Joseph A Davis; Shahadat Ahmed; Geeta V Rayasam; Balasaheb G Jadhav; Satya M Chilla; Dhrubajyoti Datta; A Gadhave; Vamshi K Tulasi; Tarun Jain; Sreedhara Voleti; Biju Benjamin; Sunitha Udupa; Garima Jain; Yogender Singh; Kona Srinivas; Vinay S Bansal; Abhijit Ray; Pradip K Bhatnagar; Ian A Cliffe

doi:10.1016/j.bmcl.2017.04.036

Approaches towards the development of chimeric DPP4/ACE inhibitors for treating metabolic syndrome

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2313-2318. doi: 10.1016/j.bmcl.2017.04.036. Epub 2017 Apr 13.

Authors

Jitendra A Sattigeri¹, Sachin Sethi², Joseph A Davis², Shahadat Ahmed², Geeta V Rayasam², Balasaheb G Jadhav², Satya M Chilla², Dhrubajyoti Datta², A Gadhave², Vamshi K Tulasi², Tarun Jain², Sreedhara Voleti², Biju Benjamin², Sunitha Udupa², Garima Jain², Yogender Singh², Kona Srinivas², Vinay S Bansal², Abhijit Ray², Pradip K Bhatnagar², Ian A Cliffe²

Affiliations

¹ New Drug Discovery Research, R&D III, Ranbaxy Laboratories Limited, Plot 20, Sector 18, Udyog Vihar, Gurgaon, Haryana 122015, India. Electronic address: jitendra.sattigeri@gmail.com.
² New Drug Discovery Research, R&D III, Ranbaxy Laboratories Limited, Plot 20, Sector 18, Udyog Vihar, Gurgaon, Haryana 122015, India.

PMID: 28442252
DOI: 10.1016/j.bmcl.2017.04.036

Abstract

Designing drug candidates exhibiting polypharmacology is one of the strategies adopted by medicinal chemists to address multifactorial diseases. Metabolic disease is one such multifactorial disorder characterized by hyperglycaemia, hypertension and dyslipidaemia among others. In this paper we report a new class of molecular framework combining the pharmacophoric features of DPP4 inhibitors with those of ACE inhibitors to afford potent dual inhibitors of DPP4 and ACE.

Keywords: DPP4-ACE dual inhibitor.

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / chemistry
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Animals
Dipeptidyl-Peptidase IV Inhibitors / chemistry
Dipeptidyl-Peptidase IV Inhibitors / pharmacology
Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
Dogs
Humans
Inhibitory Concentration 50
Metabolic Syndrome / drug therapy*
Mice
Microsomes, Liver / drug effects
Molecular Docking Simulation
Rats

Substances

Angiotensin-Converting Enzyme Inhibitors
Dipeptidyl-Peptidase IV Inhibitors