Author/Authors :
Jianhua Chao، نويسنده , , Arthur G. Taveras، نويسنده , , Jianping Chao، نويسنده , , Cynthia Aki، نويسنده , , Michael Dwyer، نويسنده , , Younong Yu، نويسنده , , Biju Purakkattle، نويسنده , , Diane Rindgen، نويسنده , , James Jakway، نويسنده , , R. William Hipkin، نويسنده , , James Fosetta، نويسنده , , Xuedong Fan، نويسنده , , Daniel Lundell، نويسنده , , Jay Fine، نويسنده , , Michael Minnicozzi، نويسنده , , Jonathan Phillips، نويسنده , , J. Robert Merritt، نويسنده ,
Abstract :
A novel series of cyclobutenedione centered C(4)-alkyl substituted furanyl analogs was developed as potent CXCR2 and CXCR1 antagonists. Compound 16 exhibits potent inhibitory activities against IL-8 binding to the receptors (CXCR2 Ki = 1 nM, IC50 = 1.3 nM; CXCR1 Ki = 3 nM, IC50 = 7.3 nM), and demonstrates potent inhibition against both Gro-α and IL-8 induced hPMN migration (chemotaxis: CXCR2 IC50 = 0.5 nM, CXCR1 IC50 = 37 nM). In addition, 16 has shown good oral pharmacokinetic profiles in rat, mouse, monkey, and dog.
