Acyl dipeptides as reversible caspase inhibitors. Part 2: Further optimization

Bioorganic and Medicinal Chemistry Letters

Volumn 12, Issue 20, 2002, Pages 2973-2975

  Linton, Steven D ^a   Karanewsky, Donald S ^a   Ternansky, Robert J ^a   Chen, Ning ^a   Guo, Xian ^a   Jahangiri, Kathy G ^a   Kalish, Vincent J ^a   Meduna, Steven P ^a   Robinson, Edward D ^a   Ullman, Brett R ^a   Wu, Joe C ^a   Pham, Brian ^a   Kodandapani, Lalitha ^a   Smidt, Robert ^a   Diaz, Jose Luis ^a   Fritz, Lawrence C ^a   Von Krosigk, U ^b   Roggo, Silvio ^b   Schmitz, Albert ^b   Tomaselli, Kevin J ^a  

^a PFIZER INC   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL DIPEPTIDE; CASPASE 3; CASPASE 6; CASPASE 7; CASPASE 8; CASPASE INHIBITOR; DIPEPTIDE DERIVATIVE; INTERLEUKIN 1BETA CONVERTING ENZYME; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG POTENCY; PEPTIDE SYNTHESIS; PROTEIN ANALYSIS;

ACYLATION; CASPASES; DIPEPTIDES; ENZYME INHIBITORS; INDICATORS AND REAGENTS; ISOENZYMES; OLIGOPEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 18644366815     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00630-3     Document Type: Article

References (20)

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16. 2O, 0°C 30 min, 1.25 h, used as crude material in coupling. The carboxylic acid used to make compound 14 was prepared from L-glutamic acid following the preceding method.
17. 2O, 4 h) after the peptide coupling and before the last 2 deprotection steps.
18. 2,-78°C 30 min, 1 h, used crude; © 1 N LiOH (2.2 equiv), 16 h, 73% overall.
19. 5 (a) Compound 20: 1-aminonaphthalene, methylbromoacetate (1.6 equiv), TEA (1.1 equiv), DMF, 60 h, used crude; Compound 21: 1-aminonaphthalene, ethyl 2-bromopropionoate (1.1 equiv), TEA (1.1 equiv), DMF, 60°C 18 h, used crude; (b) 1 N LiOH (1-1.2 equiv), 1,4-dioxane, 1.5 h. Overall yields: compound 20: 51%, compound 21: 70%.
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