Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR.

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Angell RM, Angell TD, Bamborough P, Brown D, Brown M, Buckton JB, Cockerill SG, Edwards CD, Jones KL, Longstaff T, Smee PA, Smith KJ, Somers DO, Walker AL, Willson M

Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR.

Bioorg Med Chem Lett. 2008 Jan 1;18(1):324-8. Epub 2007 Oct 17.

PubMed ID

17981461 [ View in PubMed

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Abstract

The biphenyl amides are a novel series of p38 MAP kinase inhibitors. Structure-activity relationships of the series against p38alpha are discussed with reference to the X-ray crystal structure of an example. The series was optimised rapidly to a compound showing oral activity in an in vivo disease model.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-(3-cyanophenyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)-4-biphenylcarboxamide	Mitogen-activated protein kinase 14	Ki (nM)	240	7.5	22	Details
N-(3-cyanophenyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)-4-biphenylcarboxamide	Mitogen-activated protein kinase 14	IC 50 (nM)	1500	7.5	22	Details
N-(cyclopropylmethyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxamide	Mitogen-activated protein kinase 14	Ki (nM)	480	7.5	22	Details
N-(cyclopropylmethyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxamide	Mitogen-activated protein kinase 14	IC 50 (nM)	3000	7.5	22	Details