Discovery of a potent, orally bioavailable pyrimidine VLA-4 antagonist effective in a sheep asthma model.

A series of N-(pyrimidin-4-yl)-phenylalanine VLA-4 antagonists is described. Optimization of substituents at the 2 and 5 positions of the pyrimidine ring gave 14, a very potent VLA-4 inhibitor which is orally active in a sheep asthma model.

Adipokines and vascular health in treated HIV infection: an obesity paradox?

We examined the relationship between plasma adipokine concentrations and ultrasound measures of vascular health in 100 HIV-infected adults on antiretroviral therapy. Leptin was positively correlated with flow-mediated dilation of the brachial artery and negatively with carotid intima-media thickness. These relationships were independent of traditional risk factors and trunk fat in women but not men. Neither adiponectin nor resistin was associated with either measure of vascular health.