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

James S. Scott; David J. Berry; Hayley S. Brown; Linda Buckett; David S. Clarke; Kristin Goldberg; Julian A. Hudson; Andrew G. Leach; Philip A. MacFaul; Piotr Raubo; Graeme Robb

doi:10.1039/c3md00156c

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

James S. Scott, David J. Berry, Hayley S. Brown, Linda Buckett, David S. Clarke, Kristin Goldberg, Julian A. Hudson, Andrew G. Leach, Philip A. MacFaul, Piotr Raubo, Graeme Robb

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1305-1311
Number of pages	7
Journal	MedChemComm
Volume	4
Issue number	9
DOIs	https://doi.org/10.1039/c3md00156c
Publication status	Published - Sept 2013

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10.1039/c3md00156c

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title = "Achieving improved permeability by hydrogen bond donor modulation in a series of MGAT2 inhibitors",

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.",

author = "Scott, {James S.} and Berry, {David J.} and Brown, {Hayley S.} and Linda Buckett and Clarke, {David S.} and Kristin Goldberg and Hudson, {Julian A.} and Leach, {Andrew G.} and MacFaul, {Philip A.} and Piotr Raubo and Graeme Robb",

year = "2013",

month = sep,

doi = "10.1039/c3md00156c",

language = "English",

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T1 - Achieving improved permeability by hydrogen bond donor modulation in a series of MGAT2 inhibitors

AU - Scott, James S.

AU - Berry, David J.

AU - Brown, Hayley S.

AU - Buckett, Linda

AU - Clarke, David S.

AU - Goldberg, Kristin

AU - Hudson, Julian A.

AU - Leach, Andrew G.

AU - MacFaul, Philip A.

AU - Raubo, Piotr

AU - Robb, Graeme

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

U2 - 10.1039/c3md00156c

DO - 10.1039/c3md00156c

M3 - Article

SN - 2040-2503

VL - 4

SP - 1305

EP - 1311

JO - MedChemComm

JF - MedChemComm

IS - 9

ER -

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

Abstract

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