Novel triazolopyridylbenzamides as potent and selective p38α inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 10, 2012, Pages 3431-3436

  Aiguadé, Josep ^a   Balagué, Cristina ^a   Carranco, Inés ^a   Caturla, Francisco ^a   Domínguez, María ^a   Eastwood, Paul ^a   Esteve, Cristina ^a   González, Jacob ^a   Lumeras, Wenceslao ^a,b   Orellana, Adelina ^a   Preciado, Sara ^a,c   Roca, Ramón ^a,d   Vidal, Laura ^a   Vidal, Bernat ^a  

^a Almirall SA ^*  (Spain)

^b ELI LILLY AND COMPANY   (Spain)

^c Barcelona Science Park   (Spain)

^d Barcelona Science Park   (Spain)

Author keywords

Biaryl triazolopyridine scaffold; LPS induced endotoxemia; p38 Inhibitors; Rat adjuvant induced arthritis; TNF

Indexed keywords

BENZAMIDE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE P38; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; P38 MITOGEN ACTIVATED PROTEIN KINASE ALPHA; P38 MITOGEN ACTIVATED PROTEIN KINASE ALPHA INHIBITOR; PYRIDINE DERIVATIVE; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ADJUVANT ARTHRITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CRYSTALLIZATION; DISTRIBUTION VOLUME; DOG; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; IN VIVO STUDY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

BENZAMIDES; CRYSTALLOGRAPHY, X-RAY; MITOGEN-ACTIVATED PROTEIN KINASE 14; MODELS, MOLECULAR; PROTEIN KINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

RATTUS;

EID: 84860471155     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.03.099     Document Type: Article

References (27)

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24. Compounds in this manuscript were first described in the Almirall patent application: Vidal, B.; Eastwood, P.; González, J.; Esteve, C.; PCT Int. Appl. WO2008107125, 2008.
25. During the course of this work a patent application resulting from an independent study describing triazolopyridylbenzamides as p38α inhibitors was published: see WO2008045393, 2008.
26. Coordinates and structure factors for the complex of p38α with 1 have been deposited in the RCSB Protein Data Bank (RSCB id code-rscb065714; PDB id code- 3S3I).
27. For full details of in vivo experiments performed on compounds 1 and 40 see: Balagué C.; Pont, M.; Prats, N.; Godessart, N. Br. J. Pharmacol. 2012, 165 (Epub ahead of print).