Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide
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 w...
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| Veröffentlicht in: | Journal of medicinal chemistry 1989-11, Vol.32 (11), p.2486-2492 |
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| container_issue | 11 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 32 |
| creator | Woltersdorf, O. W. Schwam, H. Bicking, J. B. Brown, S. L. DeSolms, S. J. Fishman, D. R. Graham, S. L. Gautheron, P. D. Hoffman, J. M. |
| description | 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. |
| doi_str_mv | 10.1021/jm00131a011 |
| format | Article |
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O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide</title><source>ACS Publications</source><source>MEDLINE</source><creator>Woltersdorf, O. W. ; Schwam, H. ; Bicking, J. B. ; Brown, S. L. ; DeSolms, S. J. ; Fishman, D. R. ; Graham, S. L. ; Gautheron, P. D. ; Hoffman, J. M.</creator><creatorcontrib>Woltersdorf, O. W. ; Schwam, H. ; Bicking, J. B. ; Brown, S. L. ; DeSolms, S. J. ; Fishman, D. R. ; Graham, S. L. ; Gautheron, P. D. ; Hoffman, J. M.</creatorcontrib><description>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.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00131a011</identifier><identifier>PMID: 2810337</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>6-hydroxybenzothiazole-2-sulfonamide ; Animals ; Benzothiazoles ; Carbonic Anhydrase Inhibitors - chemical synthesis ; Chemical Phenomena ; Chemistry ; Cornea - enzymology ; Ethoxzolamide - administration & dosage ; Ethoxzolamide - chemical synthesis ; Ethoxzolamide - pharmacology ; Guinea Pigs ; Humans ; Intraocular Pressure - drug effects ; Ophthalmic Solutions ; Prodrugs - administration & dosage ; Prodrugs - chemical synthesis ; Prodrugs - pharmacology ; Rabbits ; Thiazoles - administration & dosage ; Thiazoles - chemical synthesis ; Thiazoles - pharmacology</subject><ispartof>Journal of medicinal chemistry, 1989-11, Vol.32 (11), p.2486-2492</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a385t-d8bbdb0f368607a3509e3e748d4c4665bd75570c8d531e4eabc35be6b6a64d583</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm00131a011$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00131a011$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2810337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Woltersdorf, O. W.</creatorcontrib><creatorcontrib>Schwam, H.</creatorcontrib><creatorcontrib>Bicking, J. B.</creatorcontrib><creatorcontrib>Brown, S. L.</creatorcontrib><creatorcontrib>DeSolms, S. J.</creatorcontrib><creatorcontrib>Fishman, D. R.</creatorcontrib><creatorcontrib>Graham, S. L.</creatorcontrib><creatorcontrib>Gautheron, P. D.</creatorcontrib><creatorcontrib>Hoffman, J. M.</creatorcontrib><title>Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>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.</description><subject>6-hydroxybenzothiazole-2-sulfonamide</subject><subject>Animals</subject><subject>Benzothiazoles</subject><subject>Carbonic Anhydrase Inhibitors - chemical synthesis</subject><subject>Chemical Phenomena</subject><subject>Chemistry</subject><subject>Cornea - enzymology</subject><subject>Ethoxzolamide - administration & dosage</subject><subject>Ethoxzolamide - chemical synthesis</subject><subject>Ethoxzolamide - pharmacology</subject><subject>Guinea Pigs</subject><subject>Humans</subject><subject>Intraocular Pressure - drug effects</subject><subject>Ophthalmic Solutions</subject><subject>Prodrugs - administration & dosage</subject><subject>Prodrugs - chemical synthesis</subject><subject>Prodrugs - pharmacology</subject><subject>Rabbits</subject><subject>Thiazoles - administration & dosage</subject><subject>Thiazoles - chemical synthesis</subject><subject>Thiazoles - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U1r3DAQBmBRWtJN2lPPBZ3aQ9BmJFmyfQyhyRZCE9ot9Cb0ZVZb29pKdojz6-Nll9BDoac5vM_MwAxCHygsKTB6se0AKKcaKH2FFlQwIEUFxWu0AGCMMMn4W3Sa8xYAOGX8BJ2wigLn5QJ167gLVrfthLUdwoPHVicT-2Cx7jeTSzp7HPpNMGGIKS8xXeI7cmmnFjufwoPe92QcGyzJnsfHyfj-KQ6boJ9i6wkjeWyb2OsuOP8OvWl0m_37Yz1DP6-_rK9W5Pbu5uvV5S3RvBIDcZUxzkDDZSWh1FxA7bkvi8oVtpBSGFcKUYKtnODUF14by4Xx0kgtCycqfoY-HebuUvwz-jyoLmTr21b3Po5ZlTWruayL_0IqCsEqJmd4foA2xZyTb9QuhU6nSVFQ-y-ov74w64_HsaPpvHuxx7PPOTnkIQ_-8SXW6beSJS-FWt__UEBXv1bf62_qZvafD17brLZxTP18vX9ufgYQhZ5h</recordid><startdate>19891101</startdate><enddate>19891101</enddate><creator>Woltersdorf, O. W.</creator><creator>Schwam, H.</creator><creator>Bicking, J. B.</creator><creator>Brown, S. L.</creator><creator>DeSolms, S. J.</creator><creator>Fishman, D. R.</creator><creator>Graham, S. L.</creator><creator>Gautheron, P. D.</creator><creator>Hoffman, J. M.</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19891101</creationdate><title>Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide</title><author>Woltersdorf, O. W. ; Schwam, H. ; Bicking, J. B. ; Brown, S. L. ; DeSolms, S. J. ; Fishman, D. R. ; Graham, S. L. ; Gautheron, P. D. ; Hoffman, J. 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L.</au><au>Gautheron, P. D.</au><au>Hoffman, J. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1989-11-01</date><risdate>1989</risdate><volume>32</volume><issue>11</issue><spage>2486</spage><epage>2492</epage><pages>2486-2492</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><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.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>2810337</pmid><doi>10.1021/jm00131a011</doi><tpages>7</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1989-11, Vol.32 (11), p.2486-2492 |
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| subjects | 6-hydroxybenzothiazole-2-sulfonamide Animals Benzothiazoles Carbonic Anhydrase Inhibitors - chemical synthesis Chemical Phenomena Chemistry Cornea - enzymology Ethoxzolamide - administration & dosage Ethoxzolamide - chemical synthesis Ethoxzolamide - pharmacology Guinea Pigs Humans Intraocular Pressure - drug effects Ophthalmic Solutions Prodrugs - administration & dosage Prodrugs - chemical synthesis Prodrugs - pharmacology Rabbits Thiazoles - administration & dosage Thiazoles - chemical synthesis Thiazoles - pharmacology |
| title | Topically active carbonic anhydrase inhibitors. 1. O-Acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide |
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