4,4-Disubstituted piperidines, and methods of use thereof
Abstract
One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to 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, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.
Claims
exact text as granted — not AI-modified1 . A compound represented by A:
wherein R represents H, alkyl, aralkyl, cycloalkyl, alkenyl, aryl, heteroaryl, acyl, or sulfonyl; R 1 represents aryl, or heteroaryl; R 2 represents RO-alkyl, (R) 2 N-alkyl, RS-alkyl, RO-cycloalkyl, (R) 2 N-cycloalkyl, or RS-cycloalkyl; R 3 represents H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F; R 4 represents H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F; R 5 represents an aryl or heteroaryl group; R 3 and R 4 may be connected through a covalent bond; n is 0, 1, or 2; and the stereochemical configuration at any stereocenter of a compound represented by A is R, S, or a mixture of these configurations.
2 . The compound of claim 1 , wherein R 5 represents phenyl.
3 . The compound of claim 1 , wherein R 1 represents aryl.
4 . The compound of claim 1 , wherein R 2 represents RO-alkyl.
5 . The compound of claim 1 , wherein n is 1; and R 3 represents H, alkyl, or F.
6 . The compound of claim 1 , wherein n is 1; and R 4 represents H, alkyl, or F.
7 . The compound of claim 1 , wherein R 5 represents phenyl; and R 1 represents aryl.
8 . The compound of claim 1 , wherein R 5 represents phenyl; R 1 represents aryl; and R 2 represents RO-alkyl.
9 . The compound of claim 1 , wherein n is 1; R 5 represents phenyl; R 1 represents aryl; R 2 represents RO-alkyl; and R 3 represents H, alkyl, or F.
10 . The compound of claim 1 , wherein n is 1; R 5 represents phenyl; R 1 represents aryl; R 2 represents RO-alkyl; R 3 represents H, alkyl, or F; and R 4 represents H, alkyl, or F.
11 . The compound of claim 1 , wherein n is 0; and R 5 represents phenyl.
12 . The compound of claim 1 , wherein n is 0; and R 5 represents thiophene.
13 - 44 . (canceled)
45 . A formulation, comprising a compound of claim 1; and a pharmaceutically acceptable excipient.
46 . The formulation of claim 45 , wherein said pharmaceutically acceptable excipient is selected from the group consisting of cyclodextrins, celluloses, liposomes, micelle forming agents, and polymeric carriers.
47 . 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:
wherein R represents H, alkyl, aralkyl, cycloalkyl, alkenyl, aryl, heteroaryl, acyl, or sulfonyl; R 1 represents aryl, heteroaryl, aralkyl, or heteroaralkyl; R 2 represents alkyl, RO-alkyl, (R) 2 N-alkyl, RS-alkyl, cycloalkyl, RO-cycloalkyl, (R) 2 N-cycloalkyl, RS-cycloalkyl, alkenyl, aryl, or heteroaryl; R 4 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F; R 5 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F; any geminal or vicinal pairs of R 4 and R 5 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.
48 - 76 . (canceled)
77 . 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:
wherein R represents H, alkyl, aralkyl, cycloalkyl, alkenyl, aryl, heteroaryl, acyl, or sulfonyl; R 1 represents aryl, heteroaryl, aralkyl, or heteroaralkyl; R 2 represents alkyl, RO-alkyl, (R) 2 N-alkyl, RS-alkyl, cycloalkyl, RO-cycloalkyl, (R) 2 N-cycloalkyl, RS-cycloalkyl, alkenyl, aryl, or heteroaryl; R 4 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F; R 5 represents independently for each occurrence H, alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, —OR, or F; any geminal or vicinal pairs of R 4 and R 5 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.
78 - 91 . (canceled)
92 . The compound of claim 1 , wherein R 1 represents heteroaryl.Join the waitlist — get patent alerts
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