title: 3-substituted thieno[2,3-b][1,4]thiazine-6-sulfonamides. A novel class of topically active carbonic anhydrase inhibitors.
abstract: 3-Aminoalkyl derivatives of thieno[2,3-b][1,4]thiazine-6-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. The compounds described were found to be excellent in vitro inhibitors of carbonic anhydrase II and in vivo to lower intraocular pressure in three rabbit models of ocular hypertension. Compounds 20A, 20B, and 20C met the requirement of formulation as a 1% solution at pH 5.2, but none of the compounds described exhibited greater activity in the normotensive albino rabbit, the alpha-chymotrypsin-treated albino rabbit, or the normotensive pigmented rabbit than MK-927 or MK-507, the present clinical candidates.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: C A
authors.initials: CA
authors.lastname: Hunt
authors.forename: P J
authors.initials: PJ
authors.lastname: Mallorga
authors.forename: S R
authors.initials: SR
authors.lastname: Michelson
authors.forename: H
authors.initials: H
authors.lastname: Schwam
authors.forename: J M
authors.initials: JM
authors.lastname: Sondey
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
authors.forename: M F
authors.initials: MF
authors.lastname: Sugrue
authors.forename: K L
authors.initials: KL
authors.lastname: Shepard
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007429:Intraocular Pressure / Q000187:drug effects*; D008958:Models, Molecular; D011817:Rabbits; D012995:Solubility; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides