title: Synthesis and SAR of pyridazinone-substituted phenylalanine amide alpha4 integrin antagonists.
abstract: Structural modification and cellular adhesion inhibition activities of pyridazinone-substituted phenylalanine amide alpha(4) integrin antagonists are described. Functionality requirements for the arylamide moiety and the carboxylic acid group were demonstrated. The study also revealed novel structure-activity relationships (SAR) for arylated pyridazinones. A correlation between bioavailability and permeability was also explored. A selected compound showed effectiveness in a mouse leukocytosis study.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gong
authors.forename: J
authors.initials: J
authors.lastname: Kent Barbay
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kimball
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Santulli
authors.forename: M
authors.initials: M
authors.lastname: Carolyn Fisher
authors.forename: Alexey B
authors.initials: AB
authors.lastname: Dyatkin
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Miskowski
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hornby
authors.forename: Wei
authors.initials: W
authors.lastname: He
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D039441:Integrin alpha4 / Q000737:chemistry / Q000378:metabolism*; D007408:Intestinal Absorption; D007964:Leukocytosis / Q000188:drug therapy; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D011724:Pyridazines; D039441:Integrin alpha4; D010649:Phenylalanine