2-(Isopropylamino)thieno[3, 2-d]pyrimidin-4(3H)-one derivatives as selective phosphodiesterase 7 inhibitors with potent in vivo efficacy. Issue 9 (1st May 2015)

• Record Type: Journal Article
• Authors: Endo, Yusuke; Kawai, Kentaro; Asano, Takeshi; Amano, Seiji; Asanuma, Yoshihito; Sawada, Keisuke; Onodera, Yuuta; Ueo, Noriko; Takahashi, Nobuaki; Sonoda, Yo; Kamei, Noriyuki; Irie, Tetsumi
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 9(2015)
• Page Start: 1910
• Page End: 1914
• Publication Date: 2015-05-01
• Subjects: Phosphodiesterase -- Thienopyrimidinone -- T-cell -- Aqueous solubility -- Anti-inflammation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.03.031
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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, compound46 exhibited the greatest inhibition of ear edema in a phorbol ester-induced mouse model.