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1Identification of Apoptotic Caspase Inhibitors

Brett R. Ullman

2009DESIGN OF CASPASE INHIBITORS AS POTENTIAL CLINICAL AGENTS

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2Analogues de tetrapeptide

Bin Chao, Thomas L Deckwerth, Paul S Furth, Steven D Linton,Alfred P Spada,Brett R Ullman,Michael I Weinhouse

2005引用：23

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3First-In-Class Pan Caspase Inhibitor Developed for the Treatment of Liver Disease

Steven D Linton,Teresa Aja, Robert A Armstrong,Xu Bai,Long-Shiuh Chen,Ning Chen,Brett Ching, Patricia Contreras,Jose-Luis Diaz,Craig D Fisher,Lawrence C Fritz,Patricia Gladstone,

A series of oxamyl dipeptides were optimized for pan caspase inhibition, anti-apoptotic cellular activity and in vivo efficacy. This structure-activity relationship study focused on the P4 oxamides and warhead moieties. Primarily on the basis of in vitro data, inhibitors were selected for study in a murine model of alpha-Fas-induced liver injury. IDN-6556 (1) was further profiled in additional in vivo models and pharmacokinetic studies. This first-in-class caspase inhibitor is now the subject of two Phase II clinical trials, evaluating its safety and efficacy for use in liver disease.

2005Journal of medicinal chemistry（2005）引用：100

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4Tripeptides as caspase modulators

Bin Chao, Thomas L Deckwerth, Paul S Furth, Steven D Linton,Alfred P Spada,Brett R Ullman,Michael I Weinhouse

2005引用：23

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5Structure-Activity Relationships Within A Series of Caspase Inhibitors. Part 2: Heterocyclic Warheads

BR Ullman,T Aja,N Chen,JL Diaz,X Gu,J Herrmann,VJ Kalish,DS Karanewsky,L Kodandapani, JJ Krebs,SD Linton,SP Meduna,

Various heterocyclic hetero-methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A study of their structure-activity relationship (SAR) related to caspase-1, -3, -6, and -8 is reported. Their efficacy in a cellular model of cell death is also discussed. Potent broad-spectrum caspase inhibitors have been identified.

2005BIOORGANIC & MEDICINAL CHEMISTRY LETTERS（2005）引用：16

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6Oxamyl Dipeptide Caspase Inhibitors Developed for the Treatment of Stroke

SD Linton,T Aja,PR Allegrini,TL Deckwerth,JL Diaz,B Hengerer,J Herrmann,KG Jahangiri,J Kallen,DS Karanewsky,SP Meduna,K Nalley,

Structural modifications were made to a previously described acyl dipeptide caspase inhibitor, leading to the oxamyl dipeptide series. Subsequent SAR studies directed toward the warhead, P2, and P4 regions of this novel peptidomimetic are described herein.

2004Bioorganic & Medicinal Chemistry Letters（2004）引用：31

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7Structure–Activity Relationships Within a Series of Caspase Inhibitors: Effect of Leaving Group Modifications

BR Ullman,T Aja,TL Deckwerth,JL Diaz,J Herrmann,VJ Kalish,DS Karanewsky,SP Meduna,K Nalley,ED Robinson,SP Roggo,RO Sayers,

Various aryloxy methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A systematic study of their structure-activity relationship (SAR) related to caspases 1, 3, 6, and 8 is reported. Highly potent irreversible broad-spectrum caspase inhibitors have been identified. Their efficacy in cellular models of cell death and inflammation are also discussed.

2003Bioorganic & medicinal chemistry letters（2003）引用：27

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8(Substituted)acyl dipeptidyl inhibitors of the ICE/ced-3 family of cysteine proteases

Donald S Karanewsky,Vincent J Kalish,Edward D Robinson,Brett R Ullman

2003引用：61

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9Acyl Dipeptides As Reversible Caspase Inhibitors. Part 2: Further Optimization

SD Linton,DS Karanewsky,RJ Ternansky,N Chen, M Guo,KG Jahangiri,VJ Kalish,SP Meduna,ED Robinson,BR Ullman,JC Wu,B Pham,

A new structural class of broad spectrum caspase inhibitors was optimized for its activity against caspases 1, 3, 6, 7, and 8. The most potent compound had low nanomolar broad spectrum activity, in particular, single digit nanomolar inhibitory activity against caspase 8.

2002BIOORGANIC & MEDICINAL CHEMISTRY LETTERS（2002）引用：31

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10Warhead Structure-Activity Relationship Within A Series Of (1-Naphthyloxy)Acetyl-Val-Asp Hetero Methyl Ketones.

Br Ullman,Ds Karanewsky,T Aja,N Chen,Tl Deckwerth,Jl Diaz,J Herrmann,Vj Kalish,Sp Meduna,K Nalley,Ed Robinson,Ro Sayers,

2001ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY（2001）

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11New Organometallic Solutions to Problems in Polyene Natural and Unnatural Products Synthesis

Bruce H. Lipshutz,D. J. Buzard,Isaac Carrico,David Dickson,Brian James,Craig Lindsley,Sabina Pecchi,Shelly Vance,Brett R. Ullman

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

1997Organic Synthesis via Organometallics OSM 5引用：1

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