Author/Authors :
Minoru Imai، نويسنده , , Tatsuki Shiota، نويسنده , , Ken-ichiro Kataoka، نويسنده , , Christine M. Tarby، نويسنده , , Wilna J. Moree، نويسنده , , Takaharu Tsutsumi، نويسنده , , Masaki Sudo، نويسنده , , Michele M. Ramirez-Weinhouse، نويسنده , , Daniel Comer، نويسنده , , Chung-Ming Sun، نويسنده , , Shinsuke Yamagami، نويسنده , , Hiroko Tanaka، نويسنده , , Takuya Morita، نويسنده , , Takahiko Hada، نويسنده , , Jonathan Greene، نويسنده , , Doug Barnum، نويسنده , , John Saunders، نويسنده , , Peter L. Myers، نويسنده , , Yoshinori Kato، نويسنده , , Noriaki Endo، نويسنده ,
Abstract :
N,N′-Disubstituted homopiperazine derivatives have been discovered as CC-chemokine receptor 2b (CCR2b) inhibitors with submicromolar activity in the CCR2b binding assay. A 4-substituted benzyl group on one homopiperazine nitrogen was an important moiety for binding affinity to the CCR2b receptor. The SAR for CCR2b binding affinity correlated inversely with the σ factor of the functional group on this benzyl moiety. Introduction of hydroxy groups to appropriate positions in the 3,3-diphenylpropyl group on the other homopiperazine nitrogen increased CCR2b binding activity. The synthesis of an informer library to search for alternative substructures is also described.
