title: Discovery and SAR study of 2-(4-pyridylamino)thieno[3,2-d]pyrimidin-4(3H)-ones as soluble and highly potent PDE7 inhibitors.
abstract: 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.
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Asano
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Amano
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Asanuma
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sawada
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Ogura
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ueo
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Sonoda
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kamei
mesh_terms: D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D010726:Phosphodiesterase Inhibitors; D020033:Protein Isoforms; D011743:Pyrimidines; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7
keywords: Aqueous solubility; Phosphodiesterase; T-cell; Thienopyrimidinone