4,4-Disubstitued piperidines, and methods of use thereof

A method of modulating the activity of a dopamine, serotonin, or norepinephrine receptor or transporter in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of a compound represented by A:

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• wherein
• R represents H, alkyl, aralkyl, cycloalkyl, alkenyl, aryl, heteroaryl, acyl, or sulfonyl;
• R1 represents aryl, heteroaryl, aralkyl, or heteroaralkyl;
• R2 represents alkyl, RO-alkyl, (R)2N-alkyl, RS-alkyl, cycloalkyl, RO-cycloalkyl, (R)2N-cycloalkyl, RS-cycloalkyl, alkenyl, aryl, or heteroaryl;
• R4 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F;
• R5 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F;
• any geminal or vicinal pairs of R4 and R5 may be connected through a covalent bond;
• n is independently for each occurrence 0, 1, 2, 3, or 4;
• and
• the stereochemical configuration at any stereocenter of a compound represented by A is R, S, or a mixture of these configurations.

A method of modulating the activity of a dopamine receptor or transporter in a mammal, comprising the step of administering to said mammal a therapeutically effective amount of a compound represented by A:

• 59
• wherein
• R represents H, alkyl, aralkyl, cycloalkyl, alkenyl, aryl, heteroaryl, acyl, or sulfonyl;
• R1 represents aryl, heteroaryl, aralkyl, or heteroaralkyl;
• R2 represents alkyl, RO-alkyl, (R)2N-alkyl, RS-alkyl, cycloalkyl, RO-cycloalkyl, (R)2N-cycloalkyl, RS-cycloalkyl, alkenyl, aryl, or heteroaryl;
• R4 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F;
• R5 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F;
• any geminal or vicinal pairs of R4 and R5 may be connected through a covalent bond;
• n is independently for each occurrence 0, 1, 2, 3, or 4;
• and
• the stereochemical configuration at any stereocenter of a compound represented by A is R, S, or a mixture of these configurations.

A method of treating a mammal suffering from addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, or Tourette's syndrome, comprising the step of administering to said mammal a therapeutically effective amount of a compound represented by A:

• 60
• wherein
• R represents H, alkyl, aralkyl, cycloalkyl, alkenyl, aryl, heteroaryl, acyl, or sulfonyl;
• R1 represents aryl, heteroaryl, aralkyl, or heteroaralkyl;
• R2 represents alkyl, RO-alkyl, (R)2N-alkyl, RS-alkyl, cycloalkyl, RO-cycloalkyl, (R)2N-cycloalkyl, RS-cycloalkyl, alkenyl, aryl, or heteroaryl;
• R4 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F;
• R5 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F;
• any geminal or vicinal pairs of R4 and R5 may be connected through a covalent bond;
• n is independently for each occurrence 0, 1, 2, 3, or 4;
• and
• the stereochemical configuration at any stereocenter of a compound represented by A is R, S, or a mixture of these configurations.