| Autor: |
Kaila N; Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. nkaila@wyeth.com, Green N, Li HQ, Hu Y, Janz K, Gavrin LK, Thomason J, Tam S, Powell D, Cuozzo J, Hall JP, Telliez JB, Hsu S, Nickerson-Nutter C, Wang Q, Lin LL |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2007 Oct 01; Vol. 15 (19), pp. 6425-42. Date of Electronic Publication: 2007 Jul 04. |
| DOI: |
10.1016/j.bmc.2007.06.054 |
| Abstrakt: |
We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tpl2) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These compounds show good in vitro and in vivo activity against Tpl2 and improved pharmacokinetic properties. In addition they are highly selective for Tpl2 kinase over other kinases, for example, EGFR, MEK, MK2, and p38. Lead compound 4-cycloheptylamino-6-[(pyridin-3-ylmethyl)-amino]-[1,7]naphthyridine-3-carbonitrile (30) was efficacious in a rat model of LPS-induced TNF-alpha production. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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