Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity.

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Angell R, Aston NM, Bamborough P, Buckton JB, Cockerill S, deBoeck SJ, Edwards CD, Holmes DS, Jones KL, Laine DI, Patel S, Smee PA, Smith KJ, Somers DO, Walker AL

Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity.

Bioorg Med Chem Lett. 2008 Aug 1;18(15):4428-32. doi: 10.1016/j.bmcl.2008.06.048. Epub 2008 Jun 18.

PubMed ID

18614366 [ View in PubMed

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Abstract

The biphenyl amides (BPAs) are a novel series of p38alpha MAP kinase inhibitor. The optimisation of the series to give compounds that are potent in an in vivo disease model is discussed. SAR is presented and rationalised with reference to the crystallographic binding mode.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
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	N/A	N/A	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	N/A	N/A	Details
N~3~-cyclopropyl-N~4~'-(cyclopropylmethyl)-6-methylbiphenyl-3,4'-dicarboxamide	Mitogen-activated protein kinase 14	Ki (nM)	12	N/A	N/A	Details
N~3~-cyclopropyl-N~4~'-(cyclopropylmethyl)-6-methylbiphenyl-3,4'-dicarboxamide	Mitogen-activated protein kinase 14	IC 50 (nM)	75	N/A	N/A	Details
N~3~-cyclopropyl-N~4~'-(cyclopropylmethyl)-6-methylbiphenyl-3,4'-dicarboxamide	Mitogen-activated protein kinase 14	Ki (nM)	10	N/A	N/A	Details