Exploiting differences in caspase-2 and -3 S 2 subsites for selectivity: Structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors

Bioorganic and Medicinal Chemistry

Volumn 19, Issue 19, 2011, Pages 5833-5851

  Maillard, Michel C ^a   Brookfield, Frederick A ^b   Courtney, Stephen M ^b   Eustache, Florence M ^b   Gemkow, Mark J ^c   Handel, Rebecca K ^b   Johnson, Laura C ^b   Johnson, Peter D ^b   Kerry, Mark A ^b   Krieger, Florian ^c   Meniconi, Mirco ^b   Muñoz Sanjuán, Ignacio ^a   Palfrey, Jordan J ^b   Park, Hyunsun ^a   Schaertl, Sabine ^c   Taylor, Malcolm G ^b   Weddell, Derek ^b   Dominguez, Celia ^a  

^a CHDI Management Inc   (United States)

^b EVOTEC UK LTD   (United Kingdom)

^c EVOTEC AG   (Germany)

Author keywords

Caspase inhibitors; Huntington's disease; Proline derived P 2 scaffolds

Indexed keywords

2 (TERT BUTYL DIPHENYLSILANYLOXYMETHYL) 3 (2,2 DIMETHYLPROPYL) 5 OXO PYRROLIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 2 (TERT BUTYL DIPHENYLSILANYLOXYMETHYL) 3 (2,2 DIMETHYLPROPYL) PYRROLIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 2 (TERT BUTYL DIPHENYLSILANYLOXYMETHYL) 3 CYCLOHEXYL 5 OXO PYRROLIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 2 (TERT BUTYL DIPHENYLSILANYLOXYMETHYL) 3 CYCLOHEXYL PYRROLIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 2 AZIDO 3 ISOPROPXY 6 (4 METHOXYBENZYLOXY)HEXANOIC ACID ETHYL ESTER; 2 AZIDO 6 HYDROXY 3 ISOPROPOXYHEXANOIC ACID ETHYL ESTER; 3 (2,2 DIMETHYLPROPYL)PYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 (2,2 DIMETHYLPROPYL)PYRROLIDINE 1,2 DICARBOXYLIC ACID 1 TERT BUTYL ESTER; 3 (PYRIMIDIN 2 YLOXY)PYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 (PYRIMIDIN 2 YLOXY)PYRROLIDINE 1,2 DICARBOXYLIC ACID 1 TERT BUTYL ESTER; 3 CYCLOHEXYL 2 HYDROXYMETHYLPYRROLIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 3 CYCLOHEXYLPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 CYCLOPENTYLOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 CYCLOPENTYLOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER 2 METHYL ESTER; 3 HYDROXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER 2 METHYL ESTER; 3 ISOBUTOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 ISOBUTOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER 2 METHYL ESTER; 3 ISOPROXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 ISOPROXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER 2 METHYL ESTER; 3 METHOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 METHOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER 2 METHYL ESTER; 3 PHENYLPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 SEC BUTOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER; 3 SEC BUTOXYPYRROLIDINE 1,2 DICARBOXYLIC ACID 1 (9H FLUOREN 9 YLMETHYL)ESTER 2 METHYL ESTER; ACETYLVALYLASPARTYLVALYLALANYLASPARTYLALDEHYDE; CASPASE 2; CASPASE 3; CASPASE INHIBITOR; PENTAPEPTIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CELL ASSAY; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME SUBSTRATE; HUMAN; HUMAN CELL; IN VITRO STUDY; MOLECULAR MODEL; NONHUMAN; SOLID PHASE SYNTHESIS; STRUCTURE ACTIVITY RELATION;

BINDING SITES; CASPASE 2; CASPASE 3; CATALYTIC DOMAIN; CELL LINE; CYSTEINE PROTEINASE INHIBITORS; DRUG DESIGN; HUMANS; ISOQUINOLINES; MOLECULAR DYNAMICS SIMULATION; PIPERIDINES; PROLINE; SUBSTRATE SPECIFICITY;

EID: 80052936907     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2011.08.020     Document Type: Article

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