Versatile synthesis of chiral 2-substituted-5-oxo-1,2,3,4-tetrahydro-5H-1,4-benzodiazepines as novel scaffolds for peptidomimetic building

✍ Scribed by Susana Herrero; M.Teresa Garcı́a-López; Edurne Cenarruzabeitia; Joaquı́n Del Rı́o; Rosario Herranz

• Publisher: Elsevier Science
• Year: 2003
• Tongue: French
• Weight: 206 KB
• Volume: 59
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(03)00681-1

✦ Synopsis

The stereocontrolled synthesis of phenylalanine and tryptophan derived 5-oxo-1,2,3,4-tetrahydro-5H-1,4-benzodiazepine derivatives is described. This new methodology involves a modified Strecker reaction of N-Boc protected amino aldehydes and methyl anthranilate, reduction of the resulting a-amino nitriles, and lactamization. The resulting 2-substituted-5-oxo-1,2,3,4-tetrahydro-5H-1,4benzodiazepines were further functionalized at position 4 by alkylation or acylation reactions. One of these new tryptophan-derived 1,4benzodiazepines showed significant selective binding affinity at cholecystokinin CCK 1 receptors (IC 50 ¼156.5^33.2 nM).