Ligands for metabotropic glutamate receptors and inhibitors of naaladase

A method of agonizing a metabotropic glutamate receptor in a mammal, comprising the step of administering to a mammal an agonizing effective amount of a compound of the formula:

• wherein
• Bn is benzyl;
• R2 is selected from the group consisting of hydrogen, alkyl, and amino;
• and wherein the stereochemical configuration at any stereocenter of the compound is R or S or a mixture thereof.

A method of antagonizing a metabotropic glutamate receptor in a mammal, comprising the step of administering to a mammal an antagonizing effective amount of a compound of the formula:

• wherein
• Bn is benzyl;
• R2 is selected from the group consisting of hydrogen, alkyl, and amino;
• and wherein the stereochemical configuration at any stereocenter of the compound is R or S or a mixture thereof.

A method of agonizing a single subtype of metabotropic glutamate receptor in a mammal, comprising the step of administering to a mammal an agonizing effective amount of a compound of the formula:

• wherein
• Bn is benzyl;
• R2 is selected from the group consisting of hydrogen, alkyl, and amino;
• and wherein the stereochemical configuration at any stereocenter of the compound is R or S or a mixture thereof.

A method of antagonizing a single subtype of metabotropic glutamate receptor in a mammal, comprising the step of administering to a mammal an antagonizing effective amount of a compound of the formula:

• wherein
• Bn is benzyl;
• R2 is selected from the group consisting of hydrogen, alkyl, and amino;
• and wherein the stereochemical configuration at any stereocenter of the compound is R or S or a mixture thereof.

A method of treating a neurological disorder selected from the group consisting of epilepsy, ischaemia, central nervous system trauma, neuropathic pain, and chronic neurodegenerative diseases, which method comprises the step of administering to a mammal an antagonizing effective amount of a compound of formula 1:

• wherein
• X is selected from the group consisting of —C(O)—, —C(S)—, —S(O)2—, —C(R)(OR)—, and —C(R)(SR)—;
• Y is selected, independently for each occurrence, from the group consisting of (CR2)n, (NR)n, and a bond;
• Z is selected, independently for each occurrence, from the group consisting of C(R), C(NR2), and C(NHacyl);
• W is selected, independently for each occurrence, from the group consisting of (CR2)m, (NR)m, and a bond;
• G is selected, independently for each occurrence, from the group consisting of H, —COOH, —SO3H, —P(O)(OH)2, —SR, and 2-R-tetrazol-5-yl;
• R is selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, and aralkyl;
• and also including a negative charge for instances of R bonded to a heteroatom;
• m and n are integers selected, independently for each occurrence, from the range 0 to 3 inclusive.

A method of treating a neurological disorder selected from the group consisting of epilepsy, ischaemia, central nervous system trauma, neuropathic pain, and chronic neurodegenerative diseases, which method comprises the step of administering to a mammal an antagonizing effective amount of a compound of the formula 2:

• wherein
• X is selected from the group consisting of —C(O)—, —C(S)—, —P(O)(OR)—, —S(O)2—, —C(R)(OR)—, and —C(R)(SR)—;
• Y is selected, independently for each occurrence, from the group consisting of (CR2)n, (NR)n, and a bond;
• G is selected, independently for each occurrence, from the group consisting of H, —COOH, —SO3H, —P(O)(OH)2, and 2-R-tetrazol-5-yl;
• R is selected, independently for each occurrence, from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, and aralkyl;
• and also including a negative charge for instances of R bonded to a heteroatom;
• n is an integer selected, independently for each occurrence, from the range 0 to 3 inclusive.

A method of treating a neurological disorder selected from the group consisting of epilepsy, ischaemia, central nervous system trauma, neuropathic pain, and chronic neurodegenerative diseases, which method comprises the step of administering to a mammal an antagonizing effective amount of a compound of the formula:

• wherein
• Bn is benzyl;
• R2 is selected from the group consisting of hydrogen, alkyl, and amino;
• and wherein the stereochemical configuration at any stereocenter of the compound is R or S or a mixture thereof.