Linked Life Data

15177479

Source:http://linkedlifedata.com/resource/pubmed/id/15177479

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pubmed-article:15177479pubmed:abstractTextWe have expanded our previously reported series of pyrazole-based inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited examination of the SAR of this new series in both enzyme and cell based in vitro assays has revealed selectivity differences with respect to p38 MAP kinase (p38 MAPK) depending on the nature of the 'warhead' group on the dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl substituents tended to show greater selectivity against p38 MAPK than those comprised of the quinoline-4-yl moiety. We have also achieved co-crystallization and X-ray analysis of compounds 3 and 15, two potent examples of this new series, with the TbetaR-I receptor kinase domain.lld:pubmed
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pubmed-article:15177479pubmed:articleTitleSynthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain.lld:pubmed
pubmed-article:15177479pubmed:affiliationDiscovery Chemistry Research and Technology, The Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. jss.dcrt@lilly.comlld:pubmed
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