Tri- and tetra-substituted guanidines and their use as excitatory amino acid antagonists

A neuroprotecting guanidine of the formula:

• ##STR4## wherein R and R"' are independently indanyl, indenyl, a carbocyclic aryl group selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl, and anthracyl, or said carbocyclic aryl group substituted by one or more substituents, R' and R" are independently indanyl, indenyl, a C.sub.1 -C.sub.6 alkyl group, C.sub.2 -C.sub.6 alkenyl group, C.sub.2 -C.sub.6 alkynyl group, C.sub.3 -C.sub.12 cycloalkyl group, C.sub.3 -C.sub.12 cycloalkyl group substituted by one or more substituents, C.sub.5 -C.sub.12 cycloalkenyl group, C.sub.5 -C.sub.12 cycloalkenyl group substituted with one or more substituents, carbocyclic aryl group selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl, and anthracyl, said carbocyclic aryl group substituted by one or more substituents, C.sub.1 -C.sub.18 aralkyl group, or a C.sub.1 -C.sub.18 aralkyl group substituted with one or more substituents, and wherein R" can, in addition, be hydrogen;
• or a physiologically acceptable salt thereof;
• wherein said substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.3 -C.sub.15 dialkylaminoalkyl, C.sub.1 -C.sub.8 alkylthio, allyl, C.sub.1 -C.sub.18 aralkyl, C.sub.1 -C.sub.18 alkaryl, C.sub.3 -C.sub.6 cycloalkyl, aroyl selected from the group consisting of benzoyl, 1-naphthoyl, 2-naphthoyl, biphenoyl, phenanthroyl, and anthroyl, aralkoxy selected from the group consisting of C.sub.1 -C.sub.6 alkoxy groups substituted by an aryl group selected from the group consisting of phenyl, 1-napththyl, 2-naphthyl, biphenyl, phenanthryl, and anthracyl, C.sub.2 -C.sub.8 acyl, carbocyclic aryl selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl, and anthracyl, C.sub.1 -C.sub.8 alkylsulfonyl, amino, C.sub.1 -C.sub.8 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, and nitro;
• and wherein said guanidine exhibits high binding to the PCP receptor.

A guanidine having the formula:

• ##STR5## wherein:
• R and R"' are independently selected from the group consisting of:
• A) carbocyclic aryl groups selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl, and anthracyl;
• and
• B) carbocyclic aryl groups as defined in A) substituted with one or more substituents selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, and nitro;
• R' is selected from the group consisting of alkyl of 1-6 carbon atoms and carbocyclic aryl groups as in A) and B);
• and
• R" is selected from the group consisting of hydrogen, alkyl of 1-6 carbon atoms, and carbocyclic aryl groups as in A) and B);
• or physiologically acceptable salts thereof.

A guanidine having the formula:

• ##STR6## wherein:
• R and R"' are independently selected from the group consisting of:
• A) carbocyclic aryl groups selected from the group consisting of phenyl, 1-naphthyl;
• and
• B) carbocyclic aryl groups as defined in A) substituted with one or more substituents selected from the group consisting of halogen, alkyl of 1-3 carbon atoms, and nitro;
• R' is selected from the group consisting of alkyl of 1-3 carbon atoms and phenyl;
• R" is selected from the group consisting of hydrogen, alkyl of 1-3 carbon atoms, and phenyl;
• or physiologically acceptable salts thereof.

A guanidine having the formula:

• ##STR7## wherein:
• R is selected from the group consisting of 1-naphthyl, 3-methylphenyl, 3-ethylphenyl, and 3-nitrophenyl;
• R' is selected from the group consisting of methyl, ethyl and phenyl;
• R"' is selected from the group consisting of hydrogen, methyl, ethyl, and phenyl;
• and
• R"' is selected from the group consisting of 3-ethylphenyl, 2-isopropylphenyl, 1-naphthyl, 4-fluoro-1-naphthyl, and 7-fluoro-1-naphthyl;
• or physiologically acceptable salts thereof.