Identification and synthesis of a unique thiocarbazate cathepsin L inhibitor

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 1, 2008, Pages 210-214

  Myers, Michael C ^a   Shah, Parag P ^a   Diamond, Scott L ^a   Huryn, Donna M ^a   Smith III, Amos B ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Cathepsin L inhibitor; Cysteine protease inhibitor; MLSCN; Thiocarbazate

Indexed keywords

CATHEPSIN L; CATHEPSIN L INHIBITOR; CYSTEINE PROTEINASE INHIBITOR; OXADIAZOLE DERIVATIVE; THIOCARBAZATE; UNCLASSIFIED DRUG;

ARTICLE; BIOASSAY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIGH THROUGHPUT SCREENING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOLECULAR LIBRARY;

CATHEPSINS; COMBINATORIAL CHEMISTRY TECHNIQUES; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; HYDRAZINES; OXADIAZOLES; SULFHYDRYL COMPOUNDS;

EID: 37549048620     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.10.107     Document Type: Article

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29. 50 values as means ± standard deviations: (-)-11(S) 56 nM ± 4 nM; (-)-12(S) 133 nM ± 2 nM; (+)-11(R) 34 μM ± 2 μM.
30. 23 +12.8. The enantiomeric purity of both (-)-11 and (+)-11 was assayed using an OD-RH chiral column with the following LC parameters: 1.0 mL/min with a linear gradient of 90% water in acetonitrile to 10% water in acetonitrile over 15 min. Using this method, baseline separation was obtained for the enantiomers and retention times for (-)-11 and (+)-11 were 14.01 min and 13.02 min, respectively. The synthesis, outlined in Scheme 2, produced both enantiomers in >99% enantiomeric purity.
31. Shah, P. P.; Myers, M. C.; Beavers, M. P.; Purvis, J. E.; Jing, H.; Grieser, H. J.; Sharlow, E. R.; Huryn, D. M.; Cooperman, B. S.; Smith, A. B., III.; Diamond, S. L., in preparation.