Peptidoaminobenzophenones, a novel class of ring-opened derivatives of 1,4-benzodiazepines

Abstract

A series of noval peptidoaminobenzophenones has been prepared via several routes and was evaluated for CNS activity. The structure--activity relationships in the series are discussed. In general, dipeptido-N-methylaminobenzophenones showed higher activities than the corresponding NH derivatives. Some compounds had very high activities in antipentylenetetrazole and antifighting tests in mice when orally administered. Very weak toxicity was also found in these compounds. Water solubility of the peptidoaminobenzophenones and their salts were tested. Possible in these compounds. Water solubility of the peptidoaminobenzophenones and their salts were tested. Possible in vivo conversion of peptidoaminobenzophenone by enzymatic cleavage of the terminal amino acid, followed by chemical cyclization to 1,4-benzodiazepine, is also discussed. Such novel open-ring derivatives of 1,4-benzodiazepine may serve as useful CNS agents.

2-Amino-5-chlorobenzophenone

“…2-Aminobenzophenone and its derivatives are important because of their applications in heterocyclic synthesis and medicines (Walsh, 1980). 2-Aminobenzophenone has been used as the starting material for the synthesis of 1,4-benzodiazepines (Sternbach et al, 1962) and antiinflammatory agents (Ottosen et al, 2003) as well as peptidoaminobenzophenones, a class of open-ring derivatives of 1,4-benzodiazepines (Hirai et al, 1980). 2-Aminobenzophenone derivatives have also been used as antimitotic agents (Liou et al, 2002).…”

Synthesis and Properties of a Mitochondrial Peripheral Benzodiazepine Receptor Conjugate

“…in vitro, these compounds are stable, and their in vivo hydrolysis by peptidases leads to the release of a benzodiazepine precursor, which then spontaneously cyclises to yield the active drug (Scheme 1). [20][21][22] How-A C H T U N G T R E N N U N G ever, these compounds lack selectivity for cancer cells.…”

Synthesis of pyrimido[1,4]diazepin-2-one analogs and their evaluation as anticonvulsant agents

“…Dipeptidoaminobenzophenones (1) display sedative, muscle relaxant, and anticonvulsant activities, in particular against metrazol-induced seizures [Hirai et al, 1980;Williams, 1983]. In earlier studies, we reported 3alkoxycarbonylaminomethylcarbonylamino-4-benzoylpyridines (4) [Fiakpui et al, 1990], 1,3-dihydro-5-phenyl-2H-pyrido [3,4-e][1,4]diazepin-2-ones (5) [Fiakpui et al, 1993b], 3-alkoxycarbonylaminomethylcarbonylamino-2-benzoylpyridines (6), and 1,3dihydro-5-phenyl-2H-pyrido[3,2-e][1,4]diazepin-2ones (7) [Fiakpui et al, 1993a] that exhibited anticon-vulsant activities in the subcutaneous metrazol (Met) and maximal electroshock (MES) screens.…”