Pharmaceutical compositions and methods for use

A method of treating a central nervous system disorder characterized by an alteration in normal neurotransmitter release and selected from the group consisting of presenile dementia, senile dementia, Parkinsonism, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, attention deficit disorder, anxiety, dyslexia, schizophrenia, Tourette's syndrome, Pick's disease, depression, mild cognitive impairment, and pain, said method comprising administering to a subject in need thereof, an effective amount of a compound of the formula:

• wherein
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2 )qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl and substituted derivatives thereof, and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ and Z″ individually represent hydrogen or a lower alkyl;
• E, E′, E″ and E′″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —(CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, —C2(CR′R″)qOR′, —(CR′R″)qNR′R″, —OC(═O)NR′R″ and —NR′C(═O)OR′, wherein q is an integer from 1 to 6, and wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof;
• and
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2 )qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl and substituted derivatives thereof, and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ and Z″ individually represent hydrogen or a lower alkyl;
• E, E′, E″ and E′″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —(CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, C2(CR′R″)qOR′, —(CR′R″)qNR′R′, —OC(═O)NR′R″ and —NR′C(═O)OR′, wherein q is an integer from 1 to 6, and wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof;
• and
• A, A′ and A″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl functionalities.

A pharmaceutical composition incorporating a compound of the formula:

• where X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR″ where R′ and R″ are individually hydrogen or lower alkyl, an aromatic group-containing species or a substitute aromatic group-containing species, and q is an integer from 1 to 6, and R′ and R″ can be straight chain or branched alkyl, or R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ and Z″ individually represent hydrogen or lower alkyl;
• E, E′, E″ and E′″ individually represent hydrogen or a non-hydrogen substituent;
• and A, A′ and A″ are individually hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl functionalities.

A compound of the formula

• wherein
• X is selected from the group consisting of C—H, C—Cl, C—Br, and C—OR′, wherein R′ is a lower alkyl or benzyl;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ or Z″ individually represent hydrogen or a lower alkyl;
• E, E′, E″ and E′″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —(CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, —C2(CR′R″)qOR′, —(CR′R″)qNR′R″, OC(═O)NR′R″ and —NR′C(═O)OR′, wherein q is an integer from 1 to 6, and wherein R′and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof;
• and
• A, A′ and A″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl.

A compound of the formula

• wherein
• X is selected from the group consisting of C—H, C—Cl, C—Br, C—OR′, wherein R′ is a lower alkyl or benzyl;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ or Z″ is methyl;
• E, E′, E″ and E′″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —(CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, —C2(CR′R″)qOR′, —(CR′R″)qNR′R″, —OC(═O)NR′R″ and —NR′C(═O)OR′, wherein q is an integer from 1 to 6, and wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof;
• and
• A, A′ and A″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl.

A compound of the formula

• wherein
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, C—OC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl and substituted derivatives thereof, and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ or Z″ individually represent hydrogen or a lower alkyl;
• E, E′, E″ and E′″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —(CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, —C2(CR′R″)qOR′, —(CR′R″)qNR′R″, —OC(═O)NR′R″ and —NR′C(═O)OR′, wherein q is an integer from 1 to 6, and wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof,
• A, A′ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl, and
• A″ is methyl.

A pharmaceutical composition incorporating a compound of the formula:

• wherein
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl and substituted derivatives thereof, and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2 3 4, 5 65 7 or 8;
• Z′ or Z″ individually represent hydrogen or a lower alkyl;
• at least two of E, E′, E″ and E′″ are hydrogen and individually zero, one or two of E, E′, E″ and E′″ are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —(CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, —C2(CR′R″)qOR′, —(CR′R″)qNR′R″, —OC(═O)NR′R″ and —NR′C(═O)OR′, wherein q is an integer from 1 to 6, and wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof;
• and
• A, A′ and A″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl functionalities.

A pharmaceutical composition incorporating a compound of the formula:

• wherein
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof, and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ or Z″ individually represent hydrogen or a lower alkyl;
• E, E′, E″ and E′″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C.(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, (CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, —C2(CR′R″)qOR′, —(CR′R″)qNR′R″, —OC(═O)NR′R″ and —NR′C(═O)OR′, wherein q is an integer from 1 to 6, and wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof;
• and
• A, A′ and A′″ are all hydrogen.

A pharmaceutical composition incorporating a compound of the formula:

• wherein
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof, and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ or Z″ individually represent hydrogen or a lower alkyl;
• E, E′, E″ and E′″ individually are hydrogen or lower alkyl;
• and
• A, A′ and A″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl functionalities.

A pharmaceutical composition incorporating a compound of the formula:

• wherein
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2)qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• at least one of Z′ or Z″ is hydrogen;
• E, E′, E″ and E′″ individually are hydrogen or a lower alkyl;
• and
• A, A′ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl functionalities and A″ is methyl.

A pharmaceutical composition incorporating a compound of the formula:

• wherein
• X is selected from the group consisting of C—H, C—F, C—Cl, C—Br, C—I, C—R′, C—NR′R″, C—CF3, C—CN, C—NO2, C—C2R′, C—N3, C—SO2CH3, C—OR′, C—SR′, C—C(═O)NR′R″, C—NR′C(═O)R′, C—C(═O)R′, C—C(═O)OR′, C(CH2 )qOR′, C—OC(═O)R′, COC(═O)NR′R″ and C—NR′C(═O)OR′, wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof and wherein q is an integer from 1 to 6, and wherein R′ and R″ can form a cycloalkyl functionality;
• m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7 or 8;
• Z′ is hydrogen and Z″ is methyl;
• E, E′, E″ and E′″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, halo, —NR′R″, —CF3, —OH, —CN, —NO2, —C2R′, —SH, —SCH3, —N3, —SO2CH3, —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH2)qOR′, —OC(═O)R′, —(CR′R″)qOCH2C2R′, —(CR′R″)qC(═O)R′, —O(CR′R″)qC(═O)R′, —C2(CR′R″)qOR′, —(CR′R″)qNR′R″, —OC(═O)NR′R″ and —NR′C(═(O)OR′, wherein q is an integer from 1 to 6, and wherein R′ and R″ are, individually, hydrogen, a lower straight-chain alkyl, a lower branched alkyl, or an aromatic group selected from the group consisting of pyridinyl, quinolinyl, pyrimidinyl, phenyl, benzyl, and substituted derivatives thereof;
• and
• A, A′ and A″ individually are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl and substituted arylalkyl functionalities.