Author/Authors :
Robert J. Watson، نويسنده , , Daniel R. Allen، نويسنده , , Helen L. Birch، نويسنده , , Gayle A. Chapman، نويسنده , , Frances C. Galvin، نويسنده , , Louise A. Jopling، نويسنده , , Roland L. Knight، نويسنده , , Dorica Meier، نويسنده , , Kathryn Oliver، نويسنده , , Johannes W.G. Meissner، نويسنده , , David A. Owen، نويسنده , , Elizabeth J. Thomas، نويسنده , , Neil Tremayne، نويسنده , , Sophie C. Williams، نويسنده ,
Abstract :
The optimization of a series of 1-aryl-3-piperidinyl urea derivatives is described in which incorporation of tropenyl and homotropenyl moieties has led to significant improvements in activity and drug-like properties. Replacement of the central piperidine with an exo-tropanyl unit led to the identification of compound 15 which provides a combination of excellent potency against human and murine receptors, drug-like properties and pharmacokinetics, thus providing a valuable tool for the evaluation of CXCR3 antagonists in models of human disease.
