Novel methylene-linked heterocyclic EP1 receptor antagonists.

Hall A ¹,

Bit RA ,

Brown SH ,

Chowdhury A ,

Affiliations

1. Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom.
Authors
Hall A¹
(1 author)

ORCIDs linked to this article

Naylor A | 0000-0001-8539-9249

Bioorganic & Medicinal Chemistry Letters, 19 Jan 2008, 18(5):1592-1597
https://doi.org/10.1016/j.bmcl.2008.01.071 PMID: 18262416

Abstract

We describe the SAR, in terms of heterocyclic replacements, for a series of pyrazole EP(1) receptor antagonists. This study led to the identification of several aromatic heterocyclic replacements for the pyrazole in the original compound. Investigation of replacements for the methylene linker uncovered disparate SAR in the thiazole and pyridine series.

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Read article at publisher's site: https://doi.org/10.1016/j.bmcl.2008.01.071

References

Articles referenced by this article (20)

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Intestinal graft-versus-host disease: mechanisms and management.
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Structure-activity relationships of 1,5-biaryl pyrroles as EP1 receptor antagonists.
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1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists: Structure-activity relationships of 4- and 5-substituted benzoic acid derivatives.
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Article citations

Discovery of novel pyrazolo[1,5-a]pyridine-based EP₁ receptor antagonists by scaffold hopping: Design, synthesis, and structure-activity relationships.
Nishigaya Y, Umei K, Saito Y, Watanabe H, Kondo T, Kondo A, Kawamura N, Tatani K, Kohno Y, Tanaka N, Seto S
Bioorg Med Chem Lett, 27(17):4044-4050, 25 Jul 2017
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Water-promoted ortho-selective monohydroxymethylation of phenols in the NaBO2 system.
Li HJ, Wu YY, Wu QX, Wang R, Dai CY, Shen ZL, Xie CL, Wu YC
Org Biomol Chem, 12(19):3100-3107, 01 May 2014
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Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.
Hall A, Billinton A, Brown SH, Chowdhury A, Clayton NM, Giblin GM, Gibson M, Goldsmith PA, Hurst DN, Naylor A, Peet CF, Scoccitti T, Wilson AW, Winchester W
Bioorg Med Chem Lett, 19(9):2599-2603, 03 Mar 2009
Cited by: 5 articles | PMID: 19332369
Discovery of brain penetrant, soluble, pyrazole amide EP1 receptor antagonists.
Hall A, Billinton A, Bristow AK, Brown SH, Chowdhury A, Cutler L, Giblin GM, Goldsmith P, Hayhow TG, Kilford IR, Naylor A, Passingham B, Rawlings DA
Bioorg Med Chem Lett, 18(14):4027-4032, 05 Jun 2008
Cited by: 3 articles | PMID: 18571922
Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy.
Hall A, Billinton A, Brown SH, Clayton NM, Chowdhury A, Giblin GM, Goldsmith P, Hayhow TG, Hurst DN, Kilford IR, Naylor A, Passingham B, Winyard L
Bioorg Med Chem Lett, 18(11):3392-3399, 11 Apr 2008
Cited by: 17 articles | PMID: 18462938

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Small molecules (chemicals) in ChEMBL (Showing 10 of 38)

3-(2-(5-chloro-2-isobutoxyphenyl)-5-methyl-1H-pyrrol-1-yl)benzoic acid(CHEMBL - CHEMBL209800)
1-(2-(benzyloxy)-5-bromobenzyl)-5-methyl-1H-pyrazole-3-carboxylic acid(CHEMBL - CHEMBL213221)
6-(2-(2-(2,4-difluorobenzyloxy)-5-chlorophenyl)cyclopent-1-enyl)picolinic acid(CHEMBL - CHEMBL234940)
sodium 2-(5-chloro-2-isobutoxybenzyl)thiazole-4-carboxylate(CHEMBL - CHEMBL255009)
sodium 2-(2-(benzyloxy)-5-chlorobenzyl)thiazole-4-carboxylate(CHEMBL - CHEMBL255652)
sodium 5-(2-(benzyloxy)-5-chlorobenzyl)thiophene-3-carboxylate(CHEMBL - CHEMBL256674)
sodium 2-(2-(benzyloxy)-5-chlorobenzyl)oxazole-4-carboxylate(CHEMBL - CHEMBL257464)
sodium 2-(2-(benzyloxy)-5-chlorobenzyl)thiazole-5-carboxylate(CHEMBL - CHEMBL257846)
sodium 4-(2-(benzyloxy)-5-chlorobenzyl)thiazole-2-carboxylate(CHEMBL - CHEMBL258057)
sodium 5-(2-(benzyloxy)-5-chlorobenzyl)nicotinate(CHEMBL - CHEMBL258303)

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Novel methylene-linked heterocyclic EP1 receptor antagonists.

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Abstract

Full text links

References

Title not supplied

Intestinal graft-versus-host disease: mechanisms and management.

A randomised, double-blind, clinical trial comparing the efficacy of nimesulide, celecoxib and rofecoxib in osteoarthritis of the knee.

Lumiracoxib, a highly selective COX-2 inhibitor.

The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief.

Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans.

Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study.

EP1 antagonists for the treatment of inflammatory pain.

Structure-activity relationships of 1,5-biaryl pyrroles as EP1 receptor antagonists.

1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists: Structure-activity relationships of 4- and 5-substituted benzoic acid derivatives.

Citations & impact

Impact metrics

Citations of article over time

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Article citations

Discovery of novel pyrazolo[1,5-a]pyridine-based EP₁ receptor antagonists by scaffold hopping: Design, synthesis, and structure-activity relationships.

Water-promoted ortho-selective monohydroxymethylation of phenols in the NaBO2 system.

Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.

Discovery of brain penetrant, soluble, pyrazole amide EP1 receptor antagonists.

Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy.

Data

Data that cites the article

Small molecules (chemicals) in ChEMBL (Showing 10 of 38)

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Novel methylene-linked heterocyclic EP1 receptor antagonists.

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