The invention relates to new basic amino acid derivatives of general
formulae I, II and III, and the preparation and use thereof in treatment
of pain. The compounds have histogranin-like antinociceptive, morphine
potentiating and COX-2 induction modulating activities. ##STR00001##
wherein: A is -hydrogen, --(C.sub.1 C.sub.8)alkyl or --(C.sub.1
C.sub.8)alkyl substituted by hydroxy; B is --(C.sub.1
C.sub.6)alkylguanidino, --(C.sub.1 C.sub.6)alkyl(4-imidazolyl),
--(C.sub.1 C.sub.6)alkylamino, p-aminophenylalkyl(C.sub.1 C.sub.6)--,
p-guanidinophenylalkyl(C.sub.1 C.sub.6)-- or 4-pyridinylalkyl(C.sub.1
C.sub.6)--; D is --(CO)--, --(CO)--(C.sub.1 C.sub.6)alkylene or
--(C.sub.1 C.sub.6)alkylene; E is a single bond or --(C.sub.1
C.sub.6)alkylene; Z is --NH.sub.2, --NH--(C.sub.1
C.sub.6)alkylcarboxamide, --NH--(C.sub.1 C.sub.6)alkyl, --NH--(N-benzyl),
--NH-cyclo(C.sub.5 C.sub.7)alkyl, --NH-2-(1-piperidyl)ethyl,
--NH-2-(1-pyrrolidyl)ethyl, --NH-2-(1-pyridyl)ethyl,
--NH-2-(morpholino)ethyl, -morpholino, -piperidyl, --OH, --(C.sub.1
C.sub.6)alkoxy, --O-benzyl or --O-halobenzyl; R.sup.1, R.sup.2 and
R.sup.3 are, independent of one another, -hydrogen, -arylcarbonylamino,
--(C.sub.1 C.sub.6)alkoylamino, --(C.sub.1 C.sub.6)alkylamino, --(C.sub.1
C.sub.6)alkyloxy, --(C.sub.1 C.sub.6)alkylaminocarbonyl, -carboxy, --OH,
-benzoyl, -p-halogenobenzoyl, -methyl, --S-(2,4-dinitrophenyl),
--S-(3-nitro-2-pyridinesulfenyl), -sulfonyl, -trifluoromethyl, --(C.sub.1
C.sub.6)alkylaminocarbonylamino, -halo or -amino; R.sup.4 and R.sup.5
are, independent of one another, -hydrogen, --(C.sub.1 C.sub.6)alkyl,
-methyloxy, -nitro, -amino, -arylcarbonylamino, --(C.sub.1
C.sub.6)alkoylamino, --(C.sub.1 C.sub.6)alkylamino, -halo or --OH.
