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

28 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

Access to Document

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

@article{9156bd1f2d004f26bd674c5d0491dc3e,

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",

year = "2010",

month = may,

day = "15",

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

language = "English",

volume = "20",

pages = "3161--4",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

number = "10",

}

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

TY - JOUR

T1 - Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor

AU - Chambers, Laura J

AU - Stevens, Alexander J

AU - Moses, Andrew P

AU - Michel, Anton D

AU - Walter, Daryl S

AU - Davies, David J

AU - Livermore, David G

AU - Fonfria, Elena

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

PY - 2010/5/15

Y1 - 2010/5/15

N2 - 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.

AB - 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.

KW - Acetamides

KW - Administration, Oral

KW - Animals

KW - Anti-Infective Agents

KW - High-Throughput Screening Assays

KW - Humans

KW - Injections, Intravenous

KW - Purinergic P2 Receptor Antagonists

KW - Pyrazoles

KW - Rats

KW - Receptors, Purinergic P2

KW - Receptors, Purinergic P2X7

KW - Structure-Activity Relationship

U2 - 10.1016/j.bmcl.2010.03.096

DO - 10.1016/j.bmcl.2010.03.096

M3 - Article

C2 - 20399651

SN - 0960-894X

VL - 20

SP - 3161

EP - 3164

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 10

ER -