Substituted Phenethylamines With Serotoninergic And/Or Norepinephrinergic Activity
Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, and/or premature ejaculation are described.
1 . A compound of Formula 1:
or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18 are independently hydrogen or deuterium;
R 19 , R 20 , and R 21 are independently —CH 3 or —CD 3 ;
wherein the compound contains at least one deuterium atom; and has deuterium enrichment that is at least about 1%.
2 . The compound as recited in claim 1 , which is:
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
3 . The compound of claim 1 , wherein said compound is a mixture of enantiomers.
4 . The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 10%.
5 . The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 20%.
6 . The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 50%.
7 . The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 70%.
8 . The compound of claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 90%.
9 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
10 . A method of treating a disease or condition involving monoamine reuptake, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound of claim 1 .
11 . The method of claim 10 , wherein the disease or condition is an anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, or premature ejaculation.
12 . The method of claim 10 , wherein the disease or condition is a drug addition.
13 . The method of claim 12 , wherein the drug addiction is an addiction to tobacco, alcohol, marijuana, or cocaine.