title: Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation.
abstract: A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure-activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate.
authors.affiliation: Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, CA 92121, USA. william.f.vernier@pfizer.com
authors.forename: William
authors.initials: W
authors.lastname: Vernier
authors.forename: Wesley
authors.initials: W
authors.lastname: Chong
authors.forename: David
authors.initials: D
authors.lastname: Rewolinski
authors.forename: Samantha
authors.initials: S
authors.lastname: Greasley
authors.forename: Thomas
authors.initials: T
authors.lastname: Pauly
authors.forename: Morena
authors.initials: M
authors.lastname: Shaw
authors.forename: Dac
authors.initials: D
authors.lastname: Dinh
authors.forename: Rose Ann
authors.initials: RA
authors.lastname: Ferre
authors.forename: James W
authors.initials: JW
authors.lastname: Meador
authors.forename: Seiji
authors.initials: S
authors.lastname: Nukui
authors.forename: Martha
authors.initials: M
authors.lastname: Ornelas
authors.forename: Robert L
authors.initials: RL
authors.lastname: Paz
authors.forename: Eric
authors.initials: E
authors.lastname: Reyner
mesh_terms: D000818:Animals; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D011817:Rabbits; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D024402:Carbonic Anhydrase II; D002257:Carbonic Anhydrase Inhibitors; D013440:Sulfides; D013449:Sulfonamides; D000096926:Benzenesulfonamides