| 摘要 |
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. wherein: A is -hydrogen, -(C<SUB>1</SUB>-C<SUB>8</SUB>)alkyl or -(C<SUB>1</SUB>-C<SUB>8</SUB>)alkyl substituted by hydroxy; B is -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylguanidino, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkyl(4-imidazolyl), -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylamino, p-aminophenylalkyl(C<SUB>1</SUB>-C<SUB>6</SUB>)-, p-guanidinophenylalkyl(C<SUB>1</SUB>-C<SUB>6</SUB>)- or 4-pyridinylalkyl(C<SUB>1</SUB>-C<SUB>6</SUB>)-; D is -(CO)-, -(CO)-(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylene or -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylene; E is a single bond or -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylene; Z is -NH<SUB>2</SUB>, -NH-(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylcarboxamide, -NH-(C<SUB>1</SUB>-C<SUB>6</SUB>)alkyl, -NH-(N-benzyl), -NH-cyclo(C<SUB>5</SUB>-C<SUB>7</SUB>)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</SUB>-C<SUB>6</SUB>)alkoxy, -O-benzyl or -O-halobenzyl; R<SUP>1</SUP>, R<SUP>2 </SUP>and R<SUP>3 </SUP>are, independent of one another, -hydrogen, -arylcarbonylamino, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkoylamino, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylamino, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkyloxy, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylaminocarbonyl, -carboxy, -OH, -benzoyl, -p-halogenobenzoyl, -methyl, -S-(2,4-dinitrophenyl), -S-(3-nitro-2-pyridinesulfenyl), -sulfonyl, -trifluoromethyl, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylaminocarbonylamino, -halo or -amino; R<SUP>4 </SUP>and R<SUP>5 </SUP>are, independent of one another, -hydrogen, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkyl, -methyloxy, -nitro, -amino, -arylcarbonylamino, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkoylamino, -(C<SUB>1</SUB>-C<SUB>6</SUB>)alkylamino, -halo or -OH.
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