Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides

Roger J Gillespie; Samantha J Bamford; Alex Clay; Suneel Gaur; Tim Haymes; Philip S Jackson; Allan M Jordan; Burkhard Klenke; Stefania Leonardi; Jeanette Liu; Howard L Mansell; Sean Ng; Mona Saadi; Heather Simmonite; Gemma C Stratton; Richard S Todd; Douglas S Williamson; Ian A Yule

doi:10.1016/j.bmc.2009.07.078

Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides

Roger J Gillespie, Samantha J Bamford, Alex Clay, Suneel Gaur, Tim Haymes, Philip S Jackson, Allan M Jordan, Burkhard Klenke, Stefania Leonardi, Jeanette Liu, Howard L Mansell, Sean Ng, Mona Saadi, Heather Simmonite, Gemma C Stratton, Richard S Todd, Douglas S Williamson, Ian A Yule

Cancer Research UK Manchester Institute

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

Abstract

Antagonists of the human A(2A) receptor have been reported to have potential therapeutic benefit in the alleviation of the symptoms associated with neurodegenerative movement disorders such as Parkinson's disease. As part of our efforts to discover potent and selective antagonists of this receptor, we herein describe the detailed optimization and structure-activity relationships of a series of pyrimidine-4-carboxamides. These optimized derivatives display desirable physiochemical and pharmacokinetic profiles, which have led to promising oral activity in clinically relevant models of Parkinson's disease.

Original language	English
Pages (from-to)	6590-605
Number of pages	16
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	18
DOIs	https://doi.org/10.1016/j.bmc.2009.07.078
Publication status	Published - 15 Sept 2009

Keywords

Adenosine A2 Receptor Antagonists
Animals
Humans
Locomotion
Mice
Parkinson Disease
Protein Binding
Pyrimidines
Receptor, Adenosine A2A
Structure-Activity Relationship

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2009.07.078

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Gillespie, R. J., Bamford, S. J., Clay, A., Gaur, S., Haymes, T., Jackson, P. S., Jordan, A. M., Klenke, B., Leonardi, S., Liu, J., Mansell, H. L., Ng, S., Saadi, M., Simmonite, H., Stratton, G. C., Todd, R. S., Williamson, D. S., & Yule, I. A. (2009). Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides. Bioorganic and Medicinal Chemistry, 17(18), 6590-605. https://doi.org/10.1016/j.bmc.2009.07.078

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title = "Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides",

abstract = "Antagonists of the human A(2A) receptor have been reported to have potential therapeutic benefit in the alleviation of the symptoms associated with neurodegenerative movement disorders such as Parkinson's disease. As part of our efforts to discover potent and selective antagonists of this receptor, we herein describe the detailed optimization and structure-activity relationships of a series of pyrimidine-4-carboxamides. These optimized derivatives display desirable physiochemical and pharmacokinetic profiles, which have led to promising oral activity in clinically relevant models of Parkinson's disease.",

keywords = "Adenosine A2 Receptor Antagonists, Animals, Humans, Locomotion, Mice, Parkinson Disease, Protein Binding, Pyrimidines, Receptor, Adenosine A2A, Structure-Activity Relationship",

author = "Gillespie, {Roger J} and Bamford, {Samantha J} and Alex Clay and Suneel Gaur and Tim Haymes and Jackson, {Philip S} and Jordan, {Allan M} and Burkhard Klenke and Stefania Leonardi and Jeanette Liu and Mansell, {Howard L} and Sean Ng and Mona Saadi and Heather Simmonite and Stratton, {Gemma C} and Todd, {Richard S} and Williamson, {Douglas S} and Yule, {Ian A}",

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doi = "10.1016/j.bmc.2009.07.078",

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journal = "Bioorganic and Medicinal Chemistry",

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Gillespie, RJ, Bamford, SJ, Clay, A, Gaur, S, Haymes, T, Jackson, PS, Jordan, AM, Klenke, B, Leonardi, S, Liu, J, Mansell, HL, Ng, S, Saadi, M, Simmonite, H, Stratton, GC, Todd, RS, Williamson, DS & Yule, IA 2009, 'Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides', Bioorganic and Medicinal Chemistry, vol. 17, no. 18, pp. 6590-605. https://doi.org/10.1016/j.bmc.2009.07.078

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T1 - Antagonists of the human A(2A) receptor. Part 6

T2 - Further optimization of pyrimidine-4-carboxamides

AU - Gillespie, Roger J

AU - Bamford, Samantha J

AU - Clay, Alex

AU - Gaur, Suneel

AU - Haymes, Tim

AU - Jackson, Philip S

AU - Jordan, Allan M

AU - Klenke, Burkhard

AU - Leonardi, Stefania

AU - Liu, Jeanette

AU - Mansell, Howard L

AU - Ng, Sean

AU - Saadi, Mona

AU - Simmonite, Heather

AU - Stratton, Gemma C

AU - Todd, Richard S

AU - Williamson, Douglas S

AU - Yule, Ian A

PY - 2009/9/15

Y1 - 2009/9/15

N2 - Antagonists of the human A(2A) receptor have been reported to have potential therapeutic benefit in the alleviation of the symptoms associated with neurodegenerative movement disorders such as Parkinson's disease. As part of our efforts to discover potent and selective antagonists of this receptor, we herein describe the detailed optimization and structure-activity relationships of a series of pyrimidine-4-carboxamides. These optimized derivatives display desirable physiochemical and pharmacokinetic profiles, which have led to promising oral activity in clinically relevant models of Parkinson's disease.

AB - Antagonists of the human A(2A) receptor have been reported to have potential therapeutic benefit in the alleviation of the symptoms associated with neurodegenerative movement disorders such as Parkinson's disease. As part of our efforts to discover potent and selective antagonists of this receptor, we herein describe the detailed optimization and structure-activity relationships of a series of pyrimidine-4-carboxamides. These optimized derivatives display desirable physiochemical and pharmacokinetic profiles, which have led to promising oral activity in clinically relevant models of Parkinson's disease.

KW - Adenosine A2 Receptor Antagonists

KW - Animals

KW - Humans

KW - Locomotion

KW - Mice

KW - Parkinson Disease

KW - Protein Binding

KW - Pyrimidines

KW - Receptor, Adenosine A2A

KW - Structure-Activity Relationship

U2 - 10.1016/j.bmc.2009.07.078

DO - 10.1016/j.bmc.2009.07.078

M3 - Article

C2 - 19695884

SN - 0968-0896

VL - 17

SP - 6590

EP - 6605

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 18

ER -

Antagonists of the human A(2A) receptor. Part 6: Further optimization of pyrimidine-4-carboxamides

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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