16408-62-1Relevant academic research and scientific papers
Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-((S)-3-(Cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propenamide)
Johnson, Henry W.B.,Lowe, Eric,Anderl, Janet L.,Fan, Andrea,Muchamuel, Tony,Bowers, Simeon,Moebius, David C.,Kirk, Christopher,McMinn, Dustin L.
, p. 11127 - 11143 (2019/01/04)
Selective immunoproteasome inhibition is a promising approach for treating autoimmune disorders, but optimal proteolytic active site subunit inhibition profiles remain unknown. We reveal here our design of peptide epoxyketone-based selective low molecular mass polypeptide-7 (LMP7) and multicatalytic endopeptidase complex subunit-1 (MECL-1) subunit inhibitors. Utilizing these and our previously disclosed low molecular mass polypeptide-2 (LMP2) inhibitor, we demonstrate a requirement of dual LMP7/LMP2 or LMP7/MECL-1 subunit inhibition profiles for potent cytokine expression inhibition and in vivo efficacy in an inflammatory disease model. These and additional findings toward optimized solubility led the design and selection of KZR-616 disclosed here and presently in clinical trials for treatment of rheumatic disease.
NOVEL ANTIVIRAL PYRROLOPYRIDINE DERIVATIVES AND METHOD FOR PREPARING THE SAME
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Paragraph 0360; 0361; 0362, (2014/09/16)
The present invention relates to a pyrrolopyridine derivative represented by the Chemical Formula I, and a racemate or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and relates to an antiviral composition including the same as an active ingredient. The compound of the Chemical Formula I has excellent antiviral activity and selectivity for wild type and resistant HIV-1, and thereby is useful as a therapeutic agent for acquired immune deficiency syndrome (AIDS).
NOVEL ANTIVIRAL PYRROLOPYRIDINE DERIVATIVE AND A PRODUCTION METHOD FOR SAME
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Paragraph 0341; 0342; 0343, (2014/12/09)
The present invention relates to a pyrrolopyridine derivative represented by the Chemical Formula I, and a racemate or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and relates to an antiviral composition including the same as an active ingredient. The compound of the Chemical Formula I has excellent antiviral activity and selectivity for wild type and resistant HIV-1, and thereby is useful as a therapeutic agent for acquired immune deficiency syndrome (AIDS).
Geminal dialkyl derivatives of N-substituted pantothenamides: Synthesis and antibacterial activity
Akinnusi, T. Olukayode,Vong, Kenward,Auclair, Karine
experimental part, p. 2696 - 2706 (2011/06/17)
As a key precursor of coenzyme A (CoA) biosynthesis, pantothenic acid has proven to be a useful backbone to elaborate probes of this biosynthetic pathway, study CoA-utilizing systems, and design molecules with antimicrobial activity. The increasing prevalence of bacterial strains resistant to one or more antibiotics has prompted a renewed interest for molecules with a novel mode of antibacterial action such as N-substituted pantothenamides. Although numerous derivatives have been reported, most are varied at the terminal N-substituent, and fewer at the β-alanine moiety. Modifications at the pantoyl portion are limited to the addition of an ω-methyl group. We report a synthetic route to N-substituted pantothenamides with various alkyl substituents replacing the geminal dimethyl groups. Our methodology is also applicable to the synthesis of pantothenic acid, pantetheine and CoA derivatives. Here a small library of new N-substituted pantothenamides was synthesized. Most of these compounds display antibacterial activity against sensitive and resistant Staphylococcus aureus. Interestingly, replacement of the ProR methyl with an allyl group yielded a new N-substituted pantothenamide which is amongst the most potent reported so far.
Hepatitis C Virus Inhibitors
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Page/Page column 32-33, (2008/06/13)
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
Inhibitors of Hepatitis C Virus
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Page/Page column 31, (2008/12/04)
Macrocyclic peptides are disclosed having the general formula: wherein R3, R3′, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS
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Page/Page column 62-63, (2008/12/05)
Macrocyclic peptides having the general formula (I): are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
Inhibitors of Hepatitis C Virus
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Page/Page column 30, (2008/12/04)
Macrocyclic peptides are disclosed having the general formula: wherein R3, R3′, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS
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Page/Page column 60, (2008/12/05)
Macrocyclic peptides having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
Hepatitis C Virus Inhibitors
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Page/Page column 29, (2008/12/05)
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
