2-(Isopropylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as selective phosphodiesterase 7 inhibitors with potent in vivo efficacy

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...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2015-05, Vol.25 (9), p.1910-1914
Hauptverfasser:	Endo, Yusuke, Kawai, Kentaro, Asano, Takeshi, Amano, Seiji, Asanuma, Yoshihito, Sawada, Keisuke, Onodera, Yuuta, Ueo, Noriko, Takahashi, Nobuaki, Sonoda, Yo, Kamei, Noriyuki, Irie, Tetsumi
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Cyclic Nucleotide Phosphodiesterases, Type 7 - antagonists & inhibitors Cyclic Nucleotide Phosphodiesterases, Type 7 - metabolism Disease Models, Animal Dose-Response Relationship, Drug Edema - chemically induced Edema - drug therapy Male Mice Mice, Inbred ICR Models, Molecular Molecular Structure Phorbol Esters Pyrimidinones - chemical synthesis Pyrimidinones - chemistry Pyrimidinones - pharmacology Solubility Structure-Activity Relationship Substrate Specificity
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2015.03.031