title: Constraining the amide bond in N-sulfonylated dipeptide VLA-4 antagonists.
abstract: The integrin VLA-4 is implicated in several inflammatory disease states. In search of non-peptidic antagonists of VLA-4, rotational constraints were imposed on the amide bond of prototypical N-sulfonylated dipeptide VLA-4 antagonists. By judicious structural modification of the side chains, trisubstituted imidazoles with moderate binding potencies were obtained, for example, 19, VLA-4 IC(50)=237 nM.
authors.affiliation: Department of Medicinal Chemical Research, Merck Research Laboratories, Rahway, NJ, USA. linda_chang@merck.com
authors.forename: Linda L
authors.initials: LL
authors.lastname: Chang
authors.forename: Ginger X
authors.initials: GX
authors.lastname: Yang
authors.forename: Ermengilda
authors.initials: E
authors.lastname: McCauley
authors.forename: Richard A
authors.initials: RA
authors.lastname: Mumford
authors.forename: John A
authors.initials: JA
authors.lastname: Schmidt
authors.forename: William K
authors.initials: WK
authors.lastname: Hagmann
mesh_terms: D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology*; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D016029:Receptors, Very Late Antigen / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D039041:Integrin alpha4beta1; D016029:Receptors, Very Late Antigen