Discovery and SAR study of 2-(4-pyridylamino)thieno[3,2-d]pyrimidin-4(3H)-ones as soluble and highly potent PDE7 inhibitors.

Autor: Endo Y; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Kawai K; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Asano T; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Amano S; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Asanuma Y; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Sawada K; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Ogura K; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Nagata N; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Ueo N; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Takahashi N; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Sonoda Y; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan., Kamei N; Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Feb 01; Vol. 25 (3), pp. 649-53. Date of Electronic Publication: 2014 Dec 06.
DOI: 10.1016/j.bmcl.2014.11.090
Abstrakt: The discovery and SAR study of a new series of soluble and highly potent phosphodiesterase (PDE) 7 inhibitors are described herein. We explored a new lead compound with improved solubility, which led to the discovery of a 2-(4-pyridylamino)thieno[3,2-d]pyrimidin-4(3H)-one series. The introduction of 3-piperidines at the 7-position resulted in the significant enhancement of PDE7 activity. In particular, compound 32 also showed strong PDE7 inhibitory activity; good selectivity against PDE3, 4, and 5; and good aqueous solubility.
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Databáze: MEDLINE
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