G. Biagi et al., STUDIES ON SPECIFIC-INHIBITION OF BENZODIAZEPINE RECEPTOR-BINDING BY SOME C-BENZOYL-1,2,3-TRIAZOLE DERIVATIVES, Journal of pharmaceutical sciences, 82(9), 1993, pp. 893-896
Certain new (1-15) or previously described (16-25) 1,2,3-triazole deri
vatives, characterized by a C-benzoyl substituent, were synthesized an
d tested for their ability to displace [H-3]flunitrazepam from bovine
brain membrane. Compounds 11 a and ga, bearing neutral and lipophilic
substituents (phenethyl and cyclohexyl, respectively) showed the highe
r activity. The 5-benzoyl isomer 11 b presented a lower activity, equi
valent to that of the triazole acetic derivative 23, which is 4-benzyl
substituted. Generally, the carboxymethyl radical in the 1-position o
f the triazole ring decreased the activity, probably because of intram
olecular hydrogen bonding with the carbonyl function of the benzoyl su
bstituent. The N-1 unsubstituted triazole derivatives 24 and 25 were i
neffective; this result is in disagreement with our previous observati
ons. Probably these molecules interact with the receptor site by a hyd
rogen bonding acceptor group and by a bulky and lipophilic portion or
a hydrogen bonding donor function that is appropriately arranged.