338401-79-9Relevant academic research and scientific papers
Discovery of 2-(cyclopentylamino)thieno[3,2-D]pyrimidin-4(3 H)-one derivatives as a new series of potent phosphodiesterase 7 inhibitors
Kawai, Kentaro,Endo, Yusuke,Asano, Takeshi,Amano, Seiji,Sawada, Keisuke,Ueo, Noriko,Takahashi, Nobuaki,Sonoda, Yo,Nagai, Mika,Kamei, Noriyuki,Nagata, Naoya
, p. 9844 - 9854 (2014)
The discovery of a new series of potent phosphodiesterase 7 (PDE7) inhibitors is described. Novel thieno[3,2-d]pyrimidin-4(3H)-one hit compounds were identified from our chemical library. Preliminary modifications of the hit compounds were performed, resulting in the discovery of a fragment-sized compound (10) with highly improved ligand efficiency. Compound design was guided by structure-activity relationships and computational modeling. The 6-substituted derivatives of the thienopyrimidinone showed diminished activity and enzyme selectivity. However, synthesis of the 7-substituted derivatives resulted in the discovery of 28e, a desirable lead compound that selectively inhibits PDE7 with single-digit nanomolar potency while displaying potent cellular efficacy.
Discovery and SAR study of 2-(4-pyridylamino)thieno[3,2-d]pyrimidin-4(3H)-ones as soluble and highly potent PDE7 inhibitors
Endo, Yusuke,Kawai, Kentaro,Asano, Takeshi,Amano, Seiji,Asanuma, Yoshihito,Sawada, Keisuke,Ogura, Keiji,Nagata, Naoya,Ueo, Noriko,Takahashi, Nobuaki,Sonoda, Yo,Kamei, Noriyuki
, p. 649 - 653 (2015)
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.
