DC Field | Value | Language |
---|---|---|
dc.contributor.author | GHOSH, AK | ko |
dc.contributor.author | THOMPSON, WJ | ko |
dc.contributor.author | HOLLOWAY, MK | ko |
dc.contributor.author | MCKEE, SP | ko |
dc.contributor.author | DUONG, TT | ko |
dc.contributor.author | Lee, Hee Yoon | ko |
dc.contributor.author | MUNSON, PM | ko |
dc.contributor.author | SMITH, AM | ko |
dc.contributor.author | WAI, JM | 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 | 2013-02-25T23:05:04Z | - |
dc.date.available | 2013-02-25T23:05:04Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 1993-08 | - |
dc.identifier.citation | JOURNAL OF MEDICINAL CHEMISTRY, v.36, no.16, pp.2300 - 2310 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://hdl.handle.net/10203/65911 | - |
dc.description.abstract | A series of protease inhibitors bearing constrained unnatural amino acids at the P2-position and novel heterocycles at the P3-position of compound 1 (Ro 31-8959) were synthesized, and their in vitro enzyme inhibitory and antiviral activities were evaluated. Replacement of P2-asparagine of compound 1 with (2S,3'R)-tetrahydrofuranylglycine resulted in improvement in enzyme inhibitory as well as antiviral potencies (compound 23). Interestingly, incorporation of (2S,3'S)-tetrahydrofuranylglycine at the P2-position proved to be less effective. The resulting compound 24 was 100-fold less potent than the 2S,3R-isomer (compound 23). This stereochemical preference indicated a hydrogen-bonding interaction between the tetrahydrofuranyl oxygen and the residues of the S2-region of the enzyme active site. Furthermore, replacement of P3-quinolinoyl ligand of 1 with various novel heterocycles resulted in potent inhibitors of HIV proteases. Of particular interest, compound 2 with (2S,3'R)-tetrahydrofuranylglycine at P2 and pyrazine derivative at P3 is one of the most potent inhibitors of HIV-1 (IC50 value 0.07 nM) and HIV-2 (IC50 value 0.18 nM) proteases. Another important result in this series is the identification of compound 27 in which the P2-P3-amide carbonyl has been removed. The resulting compound 27 has exhibited improvement in antiviral potency while retaining the enzyme inhibitory potency similar to compound 1. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | IMMUNODEFICIENCY VIRUS PROTEASE | - |
dc.subject | ALPHA-AMINO-ACIDS | - |
dc.subject | DRUG DESIGN | - |
dc.subject | FACILE | - |
dc.subject | TARGET | - |
dc.subject | AIDS | - |
dc.title | POTENT HIV PROTEASE INHIBITORS - THE DEVELOPMENT OF TETRAHYDROFURANYLGLYCINES AS NOVEL P(2)-LIGANDS AND PYRAZINE AMIDES AS P(3)-LIGANDS | - |
dc.type | Article | - |
dc.identifier.wosid | A1993LT44200006 | - |
dc.identifier.scopusid | 2-s2.0-0027234908 | - |
dc.type.rims | ART | - |
dc.citation.volume | 36 | - |
dc.citation.issue | 16 | - |
dc.citation.beginningpage | 2300 | - |
dc.citation.endingpage | 2310 | - |
dc.citation.publicationname | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.identifier.doi | 10.1021/jm00068a006 | - |
dc.contributor.localauthor | Lee, Hee Yoon | - |
dc.contributor.nonIdAuthor | GHOSH, AK | - |
dc.contributor.nonIdAuthor | THOMPSON, WJ | - |
dc.contributor.nonIdAuthor | HOLLOWAY, MK | - |
dc.contributor.nonIdAuthor | MCKEE, SP | - |
dc.contributor.nonIdAuthor | DUONG, TT | - |
dc.contributor.nonIdAuthor | MUNSON, PM | - |
dc.contributor.nonIdAuthor | SMITH, AM | - |
dc.contributor.nonIdAuthor | WAI, JM | - |
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 | ALPHA-AMINO-ACIDS | - |
dc.subject.keywordPlus | DRUG DESIGN | - |
dc.subject.keywordPlus | FACILE | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | AIDS | - |
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