3-substituted thieno[2,3-b][1,4]thiazine-6-sulfonamides. A novel class of topically active carbonic anhydrase inhibitors

C A Hunt; P J Mallorga; S R Michelson; H Schwam; J M Sondey; R L Smith; M F Sugrue; K L Shepard

doi:10.1021/jm00028a006

3-substituted thieno[2,3-b][1,4]thiazine-6-sulfonamides. A novel class of topically active carbonic anhydrase inhibitors

J Med Chem. 1994 Jan 21;37(2):240-7. doi: 10.1021/jm00028a006.

Authors

C A Hunt¹, P J Mallorga, S R Michelson, H Schwam, J M Sondey, R L Smith, M F Sugrue, K L Shepard

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.

PMID: 8295211
DOI: 10.1021/jm00028a006

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.

MeSH terms

Administration, Topical
Animals
Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / pharmacology
Humans
In Vitro Techniques
Intraocular Pressure / drug effects*
Models, Molecular
Rabbits
Solubility
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology

Substances

Carbonic Anhydrase Inhibitors
Sulfonamides