Topically active carbonic anhydrase inhibitors. 4. [(Hydroxyalkyl)sulfonyl]benzene and [(hydroxyalkyl)sulfonyl]thiophenesulfonamides.
For several decades a tantalizing goal for the treatment of primary open-angle glaucoma has been the development of a topically active carbonic anhydrase inhibitor. Recent results from several research groups indicate that considerable progress has been made toward this objective. In this report, we present the design and synthesis of (hydroxyalkyl)sulfonyl-substituted benzene- and thiophenesulfonamides. These compounds exhibit inhibition of carbonic anhydrase II in the nanomolar range and lower intraocular pressure in the alpha-chymotrypsinized rabbit model of ocular hypertension after topical instillation.
Shepard
K L
KL
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Graham
S L
SL
Hudcosky
R J
RJ
Michelson
S R
SR
Scholz
T H
TH
Schwam
H
H
Smith
A M
AM
Sondey
J M
JM
Strohmaier
K M
KM
Smith
R L
RL
D000287:Administration, Topical; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D002918:Chymotrypsin; D005978:Glutathione / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000096926:Benzenesulfonamides
D002257:Carbonic Anhydrase Inhibitors; D002918:Chymotrypsin; D005978:Glutathione; D013449:Sulfonamides; D013876:Thiophenes; D000096926:Benzenesulfonamides