ANTAGONISTS OF SNS SODIUM CHANNELS

摘要

Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents, formula (I): R<SUP>1</SUP> represents: (a) -L-A or -L' -A' wherein L represents a bond or a C<SUB>1-</SUB>C<SUB>6 </SUB>alkyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkenyl or C<SUB>2</SUB>-C<SUB>6</SUB> alkynyl moiety, A represents a phenyl, 5- to 10-membered heteroaryl, C<SUB>3</SUB>-C<SUB>6 </SUB>carbocyclyl or 5- to 10-membered heterocyclyl group, L' represents a C<SUB>1</SUB>-C<SUB>6</SUB> alkyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkenyl or C<SUB>2</SUB>-C<SUB>6</SUB> alkynyl moiety, and A' represents -Het-A or -X-A wherein Het represents -O-, -S- or -NR'-, and X represents -CO-, -SO-, -SO<SUB>2</SUB>-, -CO-O-, -CO-S-, -CONR'-, -O-CO-, -S-CO- or -NR'-CO-, wherein R' represents hydrogen or C<SUB>1</SUB>-C<SUB>6</SUB> alkyl; (b) -L-CR(A)(A') or -L-CR(A)(L-A) wherein R is hydrogen or C<SUB>1</SUB>1-C<SUB>4</SUB> alkyl, A' is as defined above, each L is the same or different and is as defined above and each A' is the same or different and is as defined above; (c) -L-A-A' or -L-A-L-A wherein A' and L are as defined above and each A is the same or different and is as defined above; or (d) -A-Z-A wherein Z is -Het-L'-, -X-L'-, -L'-Het- or -L'-X-, wherein Het, L' and X are as defined above and each A is the same or different and is as defined above; J represents -NR<SUP>5</SUP>-, -O- or a direct bond; R<SUP>5</SUP> represents hydrogen, C<SUB>1</SUB>-C<SUB>6</SUB> alkyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkenyl or C<SUB>2</SUB>-C<SUB>6</SUB> alkynyl; R<SUP>4</SUP> is represents hydrogen, C<SUB>1</SUB>-C<SUB>6</SUB> alkyl, C<SUB>2</SUB>-C<SUB>6</SUB> alkenyl or C<SUB>2</SUB>-C<SUB>6</SUB> alkynyl; and either R<SUP>2</SUP> represents -L-A, -L-A', -L-A-A', -L-A-L-A, -L-CR(A)(L-A), -L- CR(A)(A') or -L-CR(A)(L") wherein L" is -Het-L', -X-L', -CONH<SUB>2</SUB> or -CO<SUB>2</SUB>H, and wherein A', Het, X and R are as defined above, each L is the same or different and is as defined above, each A is the same or different and is as defined above and R<SUP>3</SUP> represents hydrogen, C<SUB>1</SUB>-C<SUB>6</SUB> alkyl C<SUB>2</SUB>-C<SUB>6</SUB> alkynyl or (CO)-L', wherein L is as defined above or R<SUP>2</SUP> and R<SUP>3 </SUP>form, together with the nitrogen to which they are attached, a 5-to 10-membered heteroaryl or 5-to 10-membered heterocyclyl ring.