THIENO[2,3-B]FURAN-2-SULFONAMIDES AS TOPICAL CARBONIC-ANHYDRASE INHIBITORS

被引：26

作者：

HARTMAN, GD ^{[1
]}

HALCZENKO, W ^{[1
]}

PRUGH, JD ^{[1
]}

SMITH, RL ^{[1
]}

SUGRUE, MF ^{[1
]}

MALLORGA, P ^{[1
]}

MICHELSON, SR ^{[1
]}

RANDALL, WC ^{[1
]}

SCHWAM, H ^{[1
]}

SONDEY, JM ^{[1
]}

机构：

[1] MERCK RES LABS,DEPT OCULAR PHARMACOL,W POINT,PA 19486

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 16期

关键词：

D O I：

10.1021/jm00094a016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitro for inhibition of human carbonic anhydrase II (CA II) and ex vivo for their ability to inhibit CA H in the albino rabbit eye after topical administration. Compound 11a was found to lower intraocular pressure (IOP) in both the alpha-CT ocular hypertensive albino rabbit and the normal albino rabbit, but was ineffective at lowering IOP in a hypertensive, pigmented monkey model Since 11a was highly bound to ocular pigment, a series of less basic analogs was prepared. Examples in this series were both less extensively bound to ocular pigment and more active at reducing IOP in pigmented rabbits after topical dosing. Key examples displayed moderate reactivity toward glutathione.

引用

页码：3027 / 3033

页数：7

共 21 条

[1] INTERACTION OF DRUGS WITH OCULAR MELANIN INVITRO [J].

ATLASIK, B ;

STEPIEN, K ;

WILCZOK, T .

EXPERIMENTAL EYE RESEARCH, 1980, 30 (04) :325-331

[2] THIENOTHIOPYRAN-2-SULFONAMIDES - NOVEL TOPICALLY ACTIVE CARBONIC-ANHYDRASE INHIBITORS FOR THE TREATMENT OF GLAUCOMA [J].

BALDWIN, JJ ;

PONTICELLO, GS ;

ANDERSON, PS ;

CHRISTY, ME ;

MURCKO, MA ;

RANDALL, WC ;

SCHWAM, H ;

SUGRUE, MF ;

SPRINGER, JP ;

GAUTHERON, P ;

GROVE, J ;

MALLORGA, P ;

VIADER, MP ;

MCKEEVER, BM ;

NAVIA, MA .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (12) :2510-2513

[3] TOPICALLY ACTIVE CARBONIC-ANHYDRASE INHIBITORS .3. BENZOFURAN-SULFONAMIDE AND INDOLE-2-SULFONAMIDE [J].

GRAHAM, SL ;

HOFFMAN, JM ;

GAUTHERON, P ;

MICHELSON, SR ;

SCHOLZ, TH ;

SCHWAM, H ;

SHEPARD, KL ;

SMITH, AM ;

SMITH, RL ;

SONDEY, JM ;

SUGRUE, MF .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (02) :749-754

[4] TOPICALLY ACTIVE CARBONIC-ANHYDRASE INHIBITORS .2. BENZO[B]THIOPHENESULFONAMIDE DERIVATIVES WITH OCULAR HYPOTENSIVE ACTIVITY [J].

GRAHAM, SL ;

SHEPARD, KL ;

ANDERSON, PS ;

BALDWIN, JJ ;

BEST, DB ;

CHRISTY, ME ;

FREEDMAN, MB ;

GAUTHERON, P ;

HABECKER, CN ;

HOFFMAN, JM ;

LYLE, PA ;

MICHELSON, SR ;

PONTICELLO, GS ;

ROBB, CM ;

SCHWAM, H ;

SMITH, AM ;

SMITH, RL ;

SONDEY, JM ;

STROHMAIER, KM ;

SUGRUE, MF ;

VARGA, SL .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (12) :2548-2554

[5] A CONVENIENT SYNTHESIS OF THIENO [2,3-B] THIOPHENE [J].

GRONOWITZ, S ;

PERSSON, B .

ACTA CHEMICA SCANDINAVICA, 1967, 21 (03) :812-+

[6] THE PREPARATION OF 5-SUBSTITUTED THIENO[2,3-B]FURAN-2-SULFONAMIDES [J].

HARTMAN, GD ;

HALCZENKO, W ;

PRUGH, JD ;

WILLIAMS, TM .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1990, 27 (03) :679-682

[7] REGIOSELECTIVE GENERATION AND TRAPPING OF MONOANION AND DIANION OF 3-ARYLSULFONYL FURANS - BIDENTATE CARBANION STABILIZATION VIA SULFONES [J].

HARTMAN, GD ;

HALCZENKO, W .

TETRAHEDRON LETTERS, 1987, 28 (28) :3241-3244

[8] THE MELANIN BINDING OF DRUGS AND ITS IMPLICATIONS [J].

INGS, RMJ .

DRUG METABOLISM REVIEWS, 1984, 15 (5-6) :1183-1212

[9] BINDING OF PARAQUAT AND DIQUAT ON MELANIN [J].

LARSSON, B ;

OSKARSSON, A ;

TJALVE, H .

EXPERIMENTAL EYE RESEARCH, 1977, 25 (04) :353-359

[10] PHARMACOLOGICAL TESTING IN THE LASER-INDUCED MONKEY GLAUCOMA MODEL [J].

LEE, PY ;

PODOS, SM ;

HOWARDWILLIAMS, JR ;

SEVERIN, CH ;

ROSE, AD ;

SIEGEL, MJ .

CURRENT EYE RESEARCH, 1985, 4 (07) :775-781

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