Achieving improved permeability by hydrogen bond donor modulation in a series of MGAT2 inhibitors

Scott, J.S.; Berry, D.J.; Brown, H.S.; Buckett, L.; Clarke, D.S.; Goldberg, K.; Hudson, J.A.; Leach, A.G.; MacFaul, P.A.; Rauboa, P.; Robb, G.

Abstract

Monoacylglycerolacetyltransferase-2 (MGAT2) is a potential target for the treatment of type II diabetes. We report here the optimisation of a series of MGAT2 inhibitors with regard to their potency and permeability. Improvements in permeability, as measured by increased flux in a Caco-2 assay, were achieved through substitution at the 9-position of the core. We propose that reduction of the NH hydrogen-bond donor strength was primarily responsible for these effects.

Citation

Scott, J., Berry, D., Brown, H., Buckett, L., Clarke, D., Goldberg, K., …Robb, G. (2013). Achieving improved permeability by hydrogen bond donor modulation in a series of MGAT2 inhibitors. MedChemComm, 4(9), 1305-1311. https://doi.org/10.1039/c3md00156c

• Journal Article Type: Article
• Publication Date: Sep 1, 2013
• Deposit Date: Sep 3, 2013
• Publicly Available Date: Apr 11, 2017
• Journal: MedChemComm.
• Print ISSN: 2040-2503
• Electronic ISSN: 2040-2511
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 9
• Pages: 1305-1311
• DOI: https://doi.org/10.1039/c3md00156c
• Public URL: https://durham-repository.worktribe.com/output/1451189