Ap. Watt et al., Enantiomeric separation of a series of 1,4-benzodiazepin-2-one CCKB receptor antagonists bearing acidic substituents by chiral HPLC, J LIQ CHR R, 22(3), 1999, pp. 333-344
A series of 1,4-benzodiazepin-2-one CCKB receptor antagonists are, reported
in which substitution at C3 of the benzodiazepine by a phenyl-urea group h
earing acidic moieties has generated a chiral centre. As one of these enant
iomers is substantially more selective for the CCKB over the CCKA receptor,
an analytical separation of the enantiomers was developed to monitor the re
solution pf compounds by chemical means. It was shown that such compounds m
ay be resolved using a Pirkle-type 3,5-dinitrobenzoyl-leucine chiral statio
nary phase to give high alpha and R-S values. However, traditional mobile p
hase methodologies proved unsuccessful with these compounds which were foun
d not to elute without the addition of acetic acid. An investigation is des
cribed in which the effect of the acidic substituent, mobile phase composit
ion, including addition of acid, and temperature is discussed for such comp
ounds.