title: Carboxylic acid bioisosteres acylsulfonamides, acylsulfamides, and sulfonylureas as novel antagonists of the CXCR2 receptor.
abstract: A series of novel acylsulfonamide, acylsulfamide, and sulfonylurea bioisosteres of carboxylic acids were prepared as CXCR2 antagonists. Structure-activity relationships are reported for these series. One potent orally bioavailable inhibitor had excellent PK properties and was active in a lung injury model in hyperoxia-exposed newborn rats.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, 665 Stockton Drive, Exton, PA 19341, USA. mwinter4@prdus.jnj.com
authors.forename: Michael P
authors.initials: MP
authors.lastname: Winters
authors.forename: Carl
authors.initials: C
authors.lastname: Crysler
authors.forename: Nalin
authors.initials: N
authors.lastname: Subasinghe
authors.forename: Declan
authors.initials: D
authors.lastname: Ryan
authors.forename: Lynette
authors.initials: L
authors.lastname: Leong
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Zhao
authors.forename: Robert
authors.initials: R
authors.lastname: Donatelli
authors.forename: Edward
authors.initials: E
authors.lastname: Yurkow
authors.forename: Marie
authors.initials: M
authors.lastname: Mazzulla
authors.forename: Lisa
authors.initials: L
authors.lastname: Boczon
authors.forename: Carl L
authors.initials: CL
authors.lastname: Manthey
authors.forename: Christopher
authors.initials: C
authors.lastname: Molloy
authors.forename: Holly
authors.initials: H
authors.lastname: Raymond
authors.forename: Lynne
authors.initials: L
authors.lastname: Murray
authors.forename: Laura
authors.initials: L
authors.lastname: McAlonan
authors.forename: Bruce
authors.initials: B
authors.lastname: Tomczuk
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001682:Biological Availability; D018893:Bronchoalveolar Lavage; D002264:Carboxylic Acids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D015394:Molecular Structure; D009504:Neutrophils / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D013451:Sulfonic Acids / Q000737:chemistry*; D013453:Sulfonylurea Compounds / Q000737:chemistry*
chemical_list: D002264:Carboxylic Acids; D023063:Receptors, Interleukin-8B; D013449:Sulfonamides; D013451:Sulfonic Acids; D013453:Sulfonylurea Compounds; D003577:Cytochrome P-450 Enzyme System; C005741:sulfamic acid