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.
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.
Lauffer
David J
DJ
Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, MA 02139-4211, USA. david_lauffer@vpharm.com
Mullican
Michael D
MD
D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D018716:Molecular Mimicry
C465746:3-tert-butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D001569:Benzodiazepines