Rapid optimization of an ICE inhibitor synthesis using multiple reaction conditions in a parallel array

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 17, 1998, Pages 2309-2314

  Warmus, Joseph S ^a   Ryder, Todd R ^a   Hodges, John C ^a   Kennedy, Robert M ^a   Brady, Kenneth D ^b  

^a PFIZER INC   (United States)

^b BASF Bioresearch Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 1BETA CONVERTING ENZYME INHIBITOR;

ARTICLE; CHEMICAL REACTION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; THIN LAYER CHROMATOGRAPHY;

AMINO ACID SUBSTITUTION; ASPARTIC ACID; AUTOMATION; CASPASE 1; CYSTEINE PROTEINASE INHIBITORS; DRUG DESIGN; INDICATORS AND REAGENTS; KETONES; KINETICS; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032497394     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00418-1     Document Type: Article

References (18)

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7. 2 and 1.4 mL (1.2 equiv) of this solution added to each vial. The vials were concentrated under a stream of nitrogen. Samples of naphthylacetic acid were dissolved in the appropriate solvent (0.3 M) and 2 mL added to the correct vials. The base (2 equiv, 0.5 M solution where appropriate) and any adjuvant was added. The reactions were shaken for 12 h. At this point, aliquots were taken for analytical HPLC analysis.
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13. 2 to prepare a 0.5 M solution and dispensed to all vials and concentrated under a stream of nitrogen. Solutions of the acids in appropriate solvents were added and the reactions were shaken for 2 h. An aliquot was taken for HPLC analysis. The reactions were concentrated under a stream of nitrogen and analyzed by HPLC.
14. 2 (5×) and MeOH (5×), then dried at 50 °C under vacuum. Analysis showed the loading of the resin to be 2.17 mmol S/g.
15. 50s were reported as the mean of the (up to 4) independent determinations.
16. + + 1); Anal, calcd C 47.12, H 4.55, N5.50. Found C 46.77, H 4.69, N 5.69.
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18. 11. For references to automated reaction optimization see: Kramer, G. W.; Fuchs P. L. Chemtech 1989, 682. Frisbee, A. R.; Nantz, M. H.; Kramer, G. W.; Fuchs, P. L. J. Am. Chem. Soc. 1984 106, 7143.