Novel AT(1) receptor antagonists bearing substituted 4-phenylquinoline moieties instead of the classical biphenyl fragment were designed and synthesized as the first step of an investigation devoted to the development of new antihypertensive agents and to the understanding of the molecular basis of their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [(125)I]Sar(1),Ile(8)-Ang II specifically bound to AT(1) receptor in rat hepatic membranes. These AT(1) receptor binding studies revealed nanomolar affinity in several of the compounds under study. The most potent ligands 4b,t were found to be equipotent with losartan and possessed either a 3-tetrazolylquinoline or a 2-amino-3-quinolinecarboxylic moiety, respectively. Moreover, some selected compounds were evaluated for antagonism of Ang II-induced contraction in rabbit aortic strips, and the most potent compounds in the binding test 4b,t were slightly more potent than losartan in inhibiting Ang II-induced contraction. Finally, the most relevant structure-affinity relationship data were rationalized by means of computational studies performed on the isolated ligands as well as by computational simulations on the ligands complexed with a theoretical AT(1) receptor model.
We address the problem of autocalibration of a moving camera with unknown constant intrinsic parameters. Existing autocalibration techniques use numerical optimization algorithms whose convergence to the correct result cannot be guaranteed, in general. To address this problem, we have developed a method where an interval branch-and-bound method is employed for numerical minimization. Thanks to the properties of Interval Analysis this method converges to the global solution with mathematical certainty and arbitrary accuracy and the only input information it requires from the user are a set of point correspondences and a search interval. The cost function is based on the Huang-Faugeras constraint of the essential matrix. A recently proposed interval extension based on Bernstein polynomial forms has been investigated to speed up the search for the solution. Finally, experimental results are presented.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.