title: 2-(Isopropylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as selective phosphodiesterase 7 inhibitors with potent in vivo efficacy.
abstract: A new series of thienopyrimidinones is synthesized and evaluated as selective phosphodiesterase 7 (PDE7) inhibitors for the treatment of inflammatory diseases. The modification of the substituents on thienopyrimidinone revealed that an isopropylamino group at the 2-position was favorable for aqueous solubility. The introduction of 3-pyrrolidines at the 7-position resulted in good solubility, highly potent activity, and good PDE7 selectivity. Among the synthesized compounds, compound 46 exhibited the greatest inhibition of ear edema in a phorbol ester-induced mouse model.
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan. Electronic address: endo_yusuke@kaken.co.jp.
authors: Yusuke
authors: Y
authors: Endo
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Kentaro
authors: K
authors: Kawai
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Takeshi
authors: T
authors: Asano
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Seiji
authors: S
authors: Amano
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Yoshihito
authors: Y
authors: Asanuma
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Keisuke
authors: K
authors: Sawada
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Yuuta
authors: Y
authors: Onodera
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Noriko
authors: N
authors: Ueo
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Nobuaki
authors: N
authors: Takahashi
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Yo
authors: Y
authors: Sonoda
authors: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya Minamigawara-cho, Yamashina, Kyoto 607-8042, Japan.
authors: Noriyuki
authors: N
authors: Kamei
authors: Department of Clinical Chemistry and Informatics, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors: Tetsumi
authors: T
authors: Irie
mesh_terms: D000818:Animals; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D015394:Molecular Structure; D010703:Phorbol Esters; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: C000604996:2-(isopropylamino)thieno(3,2-d)pyrimidin-4(3H)-one; D010703:Phorbol Esters; D011744:Pyrimidinones; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517459:Pde7a protein, mouse
keywords: Anti-inflammation; Aqueous solubility; Phosphodiesterase; T-cell; Thienopyrimidinone