Indolin-2-one p38α inhibitors II: Lead optimisation

Paul Eastwood; Jacob González; Elena Gómez; Francisco Caturla; Cristina Balagué; Adelina Orellana; María Domínguez

doi:10.1016/j.bmcl.2011.07.033

Indolin-2-one p38α inhibitors II: Lead optimisation

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5270-3. doi: 10.1016/j.bmcl.2011.07.033. Epub 2011 Jul 19.

Authors

Paul Eastwood¹, Jacob González, Elena Gómez, Francisco Caturla, Cristina Balagué, Adelina Orellana, María Domínguez

Affiliation

¹ Almirall Research Center, Almirall Laboratories, Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain. paul.eastwood@almirall.com

PMID: 21813275
DOI: 10.1016/j.bmcl.2011.07.033

Abstract

Optimisation of a series of indolin-2-one p38α inhibitors was achieved via both blocking of a potential metabolic 'hot spot' and by increasing overall polarity of the lead series leading to non-cytotoxic compounds which showed improved oral bioavailabilities in the rat.

MeSH terms

Animals
Dose-Response Relationship, Drug
Humans
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology*
Mitogen-Activated Protein Kinase 14 / analysis*
Mitogen-Activated Protein Kinase 14 / metabolism
Molecular Structure
Rats
Stereoisomerism
Structure-Activity Relationship

Substances

Indoles
indolin-2-one
Mitogen-Activated Protein Kinase 14