title: Arylsulfonamide pyrimidines as VLA-4 antagonists.
abstract: A series of (S)-2-(2-(diethylamino)-5-(N-alkyl-N-sulfonamido)pyrimidin-4-ylamino)-3-(4-(carbamoyloxy)phenyl)propanoic acid is discovered as orally available VLA-4 antagonists. Representative compounds 11b and 11p showed efficacy in multiple in vivo animal models. The in vitro selectivity of 11p is also described.
authors.affiliation: Department of Chemical Sciences, Elan Pharmaceuticals, Inc., 180 Oyster Point Blvd., South San Francisco, CA 94080, USA. ying_zi_xu@yahoo.com
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Xu
authors.forename: Andrei W
authors.initials: AW
authors.lastname: Konradi
authors.forename: Frederique
authors.initials: F
authors.lastname: Bard
authors.forename: Michael
authors.initials: M
authors.lastname: Dappen
authors.forename: Lilibeth
authors.initials: L
authors.lastname: Dofiles
authors.forename: Mark
authors.initials: M
authors.lastname: Dreyer
authors.forename: Ian
authors.initials: I
authors.lastname: Gallager
authors.forename: Caroline
authors.initials: C
authors.lastname: Garrido
authors.forename: Mike
authors.initials: M
authors.lastname: Krimm
authors.forename: Zhenmei
authors.initials: Z
authors.lastname: Liao
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Messersmith
authors.forename: Linda
authors.initials: L
authors.lastname: Mutter
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pleiss
authors.forename: Bhushan
authors.initials: B
authors.lastname: Samant
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Semko
authors.forename: Jennifer
authors.initials: J
authors.lastname: Smith
authors.forename: Frank
authors.initials: F
authors.lastname: Stappenbeck
authors.forename: Brian
authors.initials: B
authors.lastname: Stupi
authors.forename: Chris
authors.initials: C
authors.lastname: Vandervert
authors.forename: Brent
authors.initials: B
authors.lastname: Welch
authors.forename: Brian
authors.initials: B
authors.lastname: Wipke
authors.forename: Ted
authors.initials: T
authors.lastname: Yednock
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001249:Asthma / Q000188:drug therapy; D002448:Cell Adhesion / Q000187:drug effects; D024043:Collagen Type II / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008968:Molecular Conformation; D009103:Multiple Sclerosis / Q000188:drug therapy; D011743:Pyrimidines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D018501:Antirheumatic Agents; D024043:Collagen Type II; D005353:Fibronectins; D039041:Integrin alpha4beta1; D011743:Pyrimidines; D013449:Sulfonamides