title: Topically active carbonic anhydrase inhibitors. 1. O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide.
abstract: A series of O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide (4, L-643,799) was prepared and the potential utility of each series member as a topically active inhibitor of ocular carbonic anhydrase was determined. In vitro studies showed these esters to be substrates for ocular esterases which liberate 4 during corneal translocation. The most interesting series member, 2-sulfamoyl-6-benzothiazolyl 2,2-dimethylpropionate (22, L-645,151), acting as a prodrug form of 4, was found to enhance delivery through the isolated albino rabbit cornea by 40-fold when compared to the parent phenol 4. Studies in rabbits revealed that 22 is a potent topically active ocular hypotensive carbonic anhydrase inhibitor.
authors: Merck Sharp & Dohme Research Laboratory, West Point, Pennsylvania 19486.
authors: O W
authors: OW
authors: Woltersdorf
authors: H
authors: H
authors: Schwam
authors: J B
authors: JB
authors: Bicking
authors: S L
authors: SL
authors: Brown
authors: S J
authors: SJ
authors: deSolms
authors: D R
authors: DR
authors: Fishman
authors: S L
authors: SL
authors: Graham
authors: P D
authors: PD
authors: Gautheron
authors: J M
authors: JM
authors: Hoffman
authors: R D
authors: RD
authors: Larson
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D003315:Cornea / Q000201:enzymology; D005016:Ethoxzolamide / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology* / Q000031:analogs & derivatives; D006168:Guinea Pigs; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D009883:Ophthalmic Solutions; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D013844:Thiazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D011355:Prodrugs; D013844:Thiazoles; C059454:6-hydroxybenzothiazide-2-sulfonamide; C044455:L 645151; D005016:Ethoxzolamide