B Jandeleit | PubMed Health

PubMed1999

Combinatorial Materials Science and Catalysis.

After forever changing the drug discovery process in the pharmaceutical industry, combinatorial chemistry methodologies are increasingly being applied to the discovery and optimization of more efficient catalysts and materials (see picture). With the advent of new combinatorial synthesis and screening technologies, coupled with integrated data management systems, the application of these technologies to materials science and catalyst research holds tremendous potential and brings high expectations to this new and exciting field.

Journal Article↗

PubMed1998

Design, synthesis and biological evaluation of nonpeptide integrin antagonists.

Recent studies demonstrated that peptide and antibody antagonists of integrin alpha v beta 3 block angiogenesis and tumor growth. In this article, the design, synthesis and biological evaluation of a series of nitroaryl ether-based, nonpeptide mimetics are described. The design of these compounds was based on Merck's arylether/alpha-aminoacid/guanidine framework and incorporates a novel nitroaryl system. The synthesized mimetics were tested against a variety of integrins (alpha v beta 3, alpha IIb beta 3, and alpha v beta 5) in order to determine their binding selectivity and ability to inhibit cell adhesion. Selected compounds were also tested for their ability to inhibit angiogenesis in vivo in the CAM (chick chorioallantoic membrane) assay. From the generated compound library, compounds 16 and 19 proved to be potent and selective inhibitors of alpha IIb beta 3 (IC50 = 14 nM) whereas compound 11 showed excellent in vivo inhibition of angiogenesis (at 30 micrograms/embryo).

Allantois↗