Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor

Laura J Chambers; Alexander J Stevens; Andrew P Moses; Anton D Michel; Daryl S Walter; David J Davies; David G Livermore; Elena Fonfria; Emmanuel H Demont; Mythily Vimal; Pam J Theobald; Paul J Beswick; Robert J Gleave; Shilina A Roman; Stefan Senger

doi:10.1016/j.bmcl.2010.03.096

Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor

Laura J Chambers, Alexander J Stevens, Andrew P Moses, Anton D Michel, Daryl S Walter, David J Davies, David G Livermore, Elena Fonfria, Emmanuel H Demont, Mythily Vimal, Pam J Theobald, Paul J Beswick, Robert J Gleave, Shilina A Roman, Stefan Senger

School of Biological Sciences

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

27 Citations (Scopus)

Abstract

High-throughput screening identified compound 1 as a potent P2X(7) receptor antagonist suitable for lead optimisation. Structure-activity relationships (SAR) of a series of (1H-pyrazol-4-yl)acetamides were investigated and compound 32 was identified as a potent P2X(7) antagonist with enhanced potency and favourable physicochemical and pharmacokinetic properties.

Original language	English
Pages (from-to)	3161-4
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	20
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2010.03.096
Publication status	Published - 15 May 2010

Keywords

Acetamides
Administration, Oral
Animals
Anti-Infective Agents
High-Throughput Screening Assays
Humans
Injections, Intravenous
Purinergic P2 Receptor Antagonists
Pyrazoles
Rats
Receptors, Purinergic P2
Receptors, Purinergic P2X7
Structure-Activity Relationship

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10.1016/j.bmcl.2010.03.096

Cite this

Chambers, L. J., Stevens, A. J., Moses, A. P., Michel, A. D., Walter, D. S., Davies, D. J., Livermore, D. G., Fonfria, E., Demont, E. H., Vimal, M., Theobald, P. J., Beswick, P. J., Gleave, R. J., Roman, S. A., & Senger, S. (2010). Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor. Bioorganic & Medicinal Chemistry Letters, 20(10), 3161-4. https://doi.org/10.1016/j.bmcl.2010.03.096

Chambers, Laura J ; Stevens, Alexander J ; Moses, Andrew P ; Michel, Anton D ; Walter, Daryl S ; Davies, David J ; Livermore, David G ; Fonfria, Elena ; Demont, Emmanuel H ; Vimal, Mythily ; Theobald, Pam J ; Beswick, Paul J ; Gleave, Robert J ; Roman, Shilina A ; Senger, Stefan. / Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor. In: Bioorganic & Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 10. pp. 3161-4.

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title = "Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor",

abstract = "High-throughput screening identified compound 1 as a potent P2X(7) receptor antagonist suitable for lead optimisation. Structure-activity relationships (SAR) of a series of (1H-pyrazol-4-yl)acetamides were investigated and compound 32 was identified as a potent P2X(7) antagonist with enhanced potency and favourable physicochemical and pharmacokinetic properties.",

keywords = "Acetamides, Administration, Oral, Animals, Anti-Infective Agents, High-Throughput Screening Assays, Humans, Injections, Intravenous, Purinergic P2 Receptor Antagonists, Pyrazoles, Rats, Receptors, Purinergic P2, Receptors, Purinergic P2X7, Structure-Activity Relationship",

author = "Chambers, {Laura J} and Stevens, {Alexander J} and Moses, {Andrew P} and Michel, {Anton D} and Walter, {Daryl S} and Davies, {David J} and Livermore, {David G} and Elena Fonfria and Demont, {Emmanuel H} and Mythily Vimal and Theobald, {Pam J} and Beswick, {Paul J} and Gleave, {Robert J} and Roman, {Shilina A} and Stefan Senger",

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doi = "10.1016/j.bmcl.2010.03.096",

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Chambers, LJ, Stevens, AJ, Moses, AP, Michel, AD, Walter, DS, Davies, DJ, Livermore, DG, Fonfria, E, Demont, EH, Vimal, M, Theobald, PJ, Beswick, PJ, Gleave, RJ, Roman, SA & Senger, S 2010, 'Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor', Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 10, pp. 3161-4. https://doi.org/10.1016/j.bmcl.2010.03.096

Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor. / Chambers, Laura J; Stevens, Alexander J; Moses, Andrew P; Michel, Anton D; Walter, Daryl S; Davies, David J; Livermore, David G; Fonfria, Elena; Demont, Emmanuel H; Vimal, Mythily; Theobald, Pam J; Beswick, Paul J; Gleave, Robert J; Roman, Shilina A; Senger, Stefan.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 20, No. 10, 15.05.2010, p. 3161-4.

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

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AU - Demont, Emmanuel H

AU - Vimal, Mythily

AU - Theobald, Pam J

AU - Beswick, Paul J

AU - Gleave, Robert J

AU - Roman, Shilina A

AU - Senger, Stefan

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KW - Injections, Intravenous

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