A practical synthesis of (S) 3-tert-butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester as a conformationally restricted dipeptido-mimetic for caspase-1 (ICE) inhibitors

David J Lauffer; Michael D Mullican

doi:10.1016/s0960-894x(02)00107-5

A practical synthesis of (S) 3-tert-butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester as a conformationally restricted dipeptido-mimetic for caspase-1 (ICE) inhibitors

Bioorg Med Chem Lett. 2002 Apr 22;12(8):1225-7. doi: 10.1016/s0960-894x(02)00107-5.

Authors

David J Lauffer¹, Michael D Mullican

Affiliation

¹ Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, MA 02139-4211, USA. david_lauffer@vpharm.com

PMID: 11934593
DOI: 10.1016/s0960-894x(02)00107-5

Abstract

A simple and versatile method for the synthesis of (S) 3-tert-butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester (4), a dipeptide mimetic, has been developed. The regioselective functionalization of the N1 and N5 ring nitrogens and the C3 amino group is demonstrated in the synthesis of an interleukin-1beta converting enzyme inhibitor 13.

MeSH terms

Benzodiazepines / chemical synthesis*
Benzodiazepines / chemistry
Benzodiazepines / pharmacology
Caspase Inhibitors*
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / chemistry
Cysteine Proteinase Inhibitors / pharmacology
Molecular Conformation
Molecular Mimicry*

Substances

3-tert-butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Benzodiazepines