title: Identification of an Orally Efficacious GPR40/FFAR1 Receptor Agonist.
abstract: GPR40/FFAR1 is a G protein-coupled receptor predominantly expressed in pancreatic β-cells and activated by long-chain free fatty acids, mediating enhancement of glucose-stimulated insulin secretion. A novel series of substituted 3-(4-aryloxyaryl)propanoic acid derivatives were prepared and evaluated for their activities as GPR40 agonists, leading to the identification of compound5, which is highly potent inin vitroassays and exhibits robust glucose lowering effects during an oral glucose tolerance test in nSTZ Wistar rat model of diabetes (ED50= 0.8 mg/kg; ED90= 3.1 mg/kg) with excellent pharmacokinetic profile, and devoid of cytochromes P450 isoform inhibitory activity.
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Sasane
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Deshmukh
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Bhadresh
authors.initials: B
authors.lastname: Rami
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Debdutta
authors.initials: D
authors.lastname: Bandyopadhyay
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Giri
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Giri
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Mukul
authors.initials: M
authors.lastname: Jain
authors.affiliation: Zydus Research Centre, Cadila Healthcare Ltd. , Sarkhej-Bavla N.H. No. 8 A, Moraiya, Ahmedabad-382 210, India.
authors.forename: Ranjit C
authors.initials: RC
authors.lastname: Desai
keywords: FFAR1; GPR40; GPR40 agonist; fatty acids; insulin secretion; type 2 diabetes