4-substituted thiophene- and furan-2-sulfonamides as topical carbonic anhydrase inhibitors.
A series of 4-substituted thiophene- and furan-2-sulfonamides was prepared and was found to possess nanomolar-level potency for inhibition of human carbonic anhydrase II in vitro. Selected examples from this group were further evaluated for their potential to act as topically effective ocular hypotensive agents in the ocular normotensive albino rabbit and the ocular alpha-chymotrypsinized rabbit. Solubility studies in water and pH 7.4 buffer were carried out to estimate the ability of compounds to be formulated in solution. The sensitization potential of key representative structures was determined by in vitro glutathione reactivity studies and guinea pig maximization testing.
Hartman
G D
GD
Merck Research Laboratories, West Point, Pennsylvania 19486.
Halczenko
W
W
Smith
R L
RL
Sugŕue
M F
MF
Mallorga
P J
PJ
Michelson
S R
SR
Randall
W C
WC
Schwam
H
H
Sondey
J M
JM
D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002256:Carbonic Anhydrases / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000201:enzymology; D005663:Furans / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D009798:Ocular Hypertension / Q000188:drug therapy; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D002257:Carbonic Anhydrase Inhibitors; D005663:Furans; D013449:Sulfonamides; D013876:Thiophenes; D002256:Carbonic Anhydrases; D005978:Glutathione; C039281:furan