DC Field | Value | Language |
---|---|---|
dc.contributor.author | GHOSH, AK | ko |
dc.contributor.author | Lee, Hee Yoon | ko |
dc.contributor.author | THOMPSON, WJ | ko |
dc.contributor.author | CULBERSON, C | ko |
dc.contributor.author | HOLLOWAY, MK | ko |
dc.contributor.author | MCKEE, SP | ko |
dc.contributor.author | MUNSON, PM | ko |
dc.contributor.author | DUONG, TT | ko |
dc.contributor.author | SMITH, AM | ko |
dc.contributor.author | DARKE, PL | ko |
dc.contributor.author | ZUGAY, JA | ko |
dc.contributor.author | EMINI, EA | ko |
dc.contributor.author | SCHLEIF, WA | ko |
dc.contributor.author | HUFF, JR | ko |
dc.contributor.author | ANDERSON, PS | ko |
dc.date.accessioned | 2013-02-24T09:19:14Z | - |
dc.date.available | 2013-02-24T09:19:14Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 1994-04 | - |
dc.identifier.citation | JOURNAL OF MEDICINAL CHEMISTRY, v.37, no.8, pp.1177 - 1188 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://hdl.handle.net/10203/56026 | - |
dc.description.abstract | Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S-2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P-2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that the urethane of 3(S)-hydroxysulfolane further increased the in vitro potency of these inhibitors. Furthermore, introduction of a small 2-alkyl group cis to the 3-hydroxyl group of either heterocyclic system further enhanced enzyme affinity. The cis-2-isopropyl group thus far offered optimum enhancement of the inhibitory properties. This led to the discovery of inhibitor 43 (IC50 3.5 nM, CIC95 50+/-14 nM) of comparable in vitro antiviral potency to the current clinical candidate 1 (Ro 31-8959) but of reduced molecular weight due to the exclusion of the P-3 quinoline ligand. Also, it has been demonstrated that the octahydropyrindene derivative 34 is an effective replacement of the P-1' decahydroisoquinoline derivative. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | IMMUNODEFICIENCY VIRUS PROTEASE | - |
dc.subject | PROTEINASE-INHIBITORS | - |
dc.subject | DESIGN | - |
dc.subject | ALKOXYCARBONYLATION | - |
dc.subject | CARBONATE | - |
dc.subject | TARGET | - |
dc.subject | FACILE | - |
dc.subject | AMINES | - |
dc.subject | AIDS | - |
dc.subject | ACID | - |
dc.title | THE DEVELOPMENT OF CYCLIC SULFOLANES AS NOVEL AND HIGH-AFFINITY P(2) LIGANDS FOR HIV-1 PROTEASE INHIBITORS | - |
dc.type | Article | - |
dc.identifier.wosid | A1994NG93600016 | - |
dc.identifier.scopusid | 2-s2.0-0028207394 | - |
dc.type.rims | ART | - |
dc.citation.volume | 37 | - |
dc.citation.issue | 8 | - |
dc.citation.beginningpage | 1177 | - |
dc.citation.endingpage | 1188 | - |
dc.citation.publicationname | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.identifier.doi | 10.1021/jm00034a016 | - |
dc.contributor.localauthor | Lee, Hee Yoon | - |
dc.contributor.nonIdAuthor | GHOSH, AK | - |
dc.contributor.nonIdAuthor | THOMPSON, WJ | - |
dc.contributor.nonIdAuthor | CULBERSON, C | - |
dc.contributor.nonIdAuthor | HOLLOWAY, MK | - |
dc.contributor.nonIdAuthor | MCKEE, SP | - |
dc.contributor.nonIdAuthor | MUNSON, PM | - |
dc.contributor.nonIdAuthor | DUONG, TT | - |
dc.contributor.nonIdAuthor | SMITH, AM | - |
dc.contributor.nonIdAuthor | DARKE, PL | - |
dc.contributor.nonIdAuthor | ZUGAY, JA | - |
dc.contributor.nonIdAuthor | EMINI, EA | - |
dc.contributor.nonIdAuthor | SCHLEIF, WA | - |
dc.contributor.nonIdAuthor | HUFF, JR | - |
dc.contributor.nonIdAuthor | ANDERSON, PS | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | IMMUNODEFICIENCY VIRUS PROTEASE | - |
dc.subject.keywordPlus | PROTEINASE-INHIBITORS | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordPlus | ALKOXYCARBONYLATION | - |
dc.subject.keywordPlus | CARBONATE | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | FACILE | - |
dc.subject.keywordPlus | AMINES | - |
dc.subject.keywordPlus | AIDS | - |
dc.subject.keywordPlus | ACID | - |
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