Deuterium-Enriched Alkyl Sulfonamides and Uses Thereof

• US 20140221395A1
• Filed: 07/30/2013
• Published: 08/07/2014
• Est. Priority Date: 08/10/2009
• Status: Active Grant

• Current Assignee: Daljit Singh Dhanoa
• Original Assignee: Daljit Singh Dhanoa
• Inventors: Dhanoa, Daljit Singh
• Granted Patent: US 8,927,553 B2
• Time in Patent Office: Days
• US Class Current: 514/255.03
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07D 295/135 with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/155 with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

Abstract

The present invention is concerned with deuterium-enriched sulfonamides of formula 1, their pharmaceutically acceptable salts and methods of use thereof for the treatment of anxiety disorders including, General Anxiety Disorder (GAD), Panic Disorder (PD), Post-Traumatic Stress Disorder (PTSD), Social Phobia (SP), Health Anxiety (Hypochondriasis), depression, major depressive disorders, unipolar depression, bipolar I depression disorder, bipolar II depression disorder, treatment-resistant depression, single episodic and recurrent major depressive disorders, depression in the medically ill, attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), Obsessive-Compulsive Disorder (OCD), Obsessive-Compulsive Personality Disorder (OCPD), Autism Spectrum Disorder (ASD), schizophrenia, psychosis, epilepsy, seizures, hot flashes due to menopause, age-related macular degeneration (AMD), premature ejaculation, male erectile dysfunction, sexual dysfunction, obesity, eating disorders, bulimia nervosa, anorexia nervosa, angina, migraine, pain, nociception, sleep disorders, insomnia, fibromyalgia, alcohol withdrawal, autism, Rett'"'"'s syndrome, cyclothymic disorder, neural injury, neurodegenerative diseases, Parkinson'"'"'s disease, Parkinson'"'"'s disease psychosis, Huntington disease, Alzheimer'"'"'s disease, frontotemporal dementia, cognitive impairment associated with age-related dementia, Alzheimer'"'"'s disease, schizophrenia, psychosis, depression, pain or discomfort associated with surgery and pain or discomfort associated with medical illness.

Claims

1. A method of treating a disease or disorder selected from the group consisting of

anxiety disorders, General Anxiety Disorder (GAD), Panic Disorder (PD), Post-Traumatic Stress Disorder (PTSD), Social Phobia (SP), Health Anxiety (Hypochondriasis), depression, major depressive disorders, unipolar depression, bipolar I depression disorder, bipolar II depression disorder, treatment-resistant depression, single episodic and recurrent major depressive disorders, depression in the medically ill, attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), Obsessive-Compulsive Disorder (OCD), Obsessive-Compulsive Personality Disorder (OCPD), Autism Spectrum Disorder (ASD), schizophrenia, psychosis, epilepsy, seizures, hot flashes due to menopause, age-related macular degeneration (AMD), premature ejaculation, male erectile dysfunction, sexual dysfunction, obesity, eating disorders, bulimia nervosa, anorexia nervosa, smoking cessation, angina, migraine, pain, nociception, sleep disorders, insomnia, fibromyalgia, alcohol withdrawal, autism, Rett'"'"'s syndrome, cyclothymic disorder, neural injury, neurodegenerative diseases, Parkinson'"'"'s disease, Parkinson'"'"'s disease psychosis, Huntington disease, Alzheimer'"'"'s disease, frontotemporal dementia, cognitive impairment associated with age-related dementia, pain or discomfort associated with surgery and pain or discomfort associated with medical illness, by administering a pharmaceutically effective dose of a deuterium-enriched compound of formula 1, or a pharmaceutically acceptable salt thereof,

2. A deuterium enriched compound of claim 1, or the pharmaceutically acceptable salts thereof wherein a compound is selected from the group consisting of

3. The method of claim 1 wherein the disease or disorder is selected from the group consisting of anxiety disorders, General Anxiety Disorder (GAD), Panic Disorder (PD), Post-Traumatic Stress Disorder (PTSD), Social Phobia (SP), Health Anxiety (Hypochondriasis), depression, major depressive disorders, unipolar depression, bipolar I depression disorder, bipolar II depression disorder, treatment-resistant depression, single episodic and recurrent major depressive disorders, depression in the medically ill, attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), epilepsy, partial epilepsy, temporal lobes epilepsy, seizures, hot flashes due to menopause, age-related macular degeneration (AMD), premature ejaculation, obesity, eating disorders, bulimia nervosa, anorexia nervosa, Parkinson'"'"'s disease, Parkinson'"'"'s disease psychosis, and smoking cessation.

4. The method of claim 3 wherein the disease or disorders are attention deficit hyperactivity disorder (ADHD) and attention deficit disorder.

5. The method of claim 4 wherein the compound of claim 1, or a pharmaceutically acceptable salt thereof is administered in combination with a drug selected from the group consisting of caffeine, amphetamine, dextroamphetamine, L-lysine-D-amphetamine and methylphenidate

6. The method of claim 3 wherein the disease is age-related macular degeneration (AMD).

7. The method of claim 6 wherein the compound of claim 1, or pharmaceutically acceptable salt thereof, is administered in combination with a vascular endothelial growth factor (VEGF) inhibitor selected from the group consisting of pegaptinib, vatalinib, and pazopanib.

8. The method of claim 6 wherein the compound of claim 1, or pharmaceutically acceptable salt thereof, is administered in with a sphingosine 1-phosphate (S1P₁) agonist selected from the group consisting of fingolimod, ponesimod, and 2-amino-2-(5-(5-(3-chloro-4-propoxyphenyl)-1,2,4-oxadiazol-3-yl)benzofuran-2-yl)propane-1,3-diol.

9. The method of claim 3 wherein the disease treated is selected from the group consisting of epilepsy, partial epilepsy, temporal lobes epilepsy, and seizures.

10. The method of claim 9 wherein the compound of claim 1 or a pharmaceutically acceptable salt, is administered with one or more drugs selected from the group consisting of phenyloin, sodium valproate, carbamazepine, phenobarbital, pregabalin, gabapentin, topamax, tiagabine, vigabetrin, oxcarbazepine, levitracetam, eslicarbazepine acetate, and lamotrigine.

11. The method of claim 3 wherein the disease or disorder is premature ejaculation.

12. The method of claim 11 wherein the compound of claim 1 or a pharmaceutically acceptable salt, is administered with a selective serotonin reuptake inhibitors (SSRI) selected from the group consisting of dapoxetine, fluoxetine, paroxetine, sertraline, citalopram, (S)-citalopram and bupropion.

13. The method of claim 3 wherein the disease is Parkinson'"'"'s disease and Parkinson'"'"'s disease psychosis.

14. The method of claim 3 wherein the disease or disorder is selected from obesity, eating disorders, bulimia nervosa and anorexia nervosa.

15. The method of claim 14 wherein the compound of claim 1 or a pharmaceutically acceptable salt, is administered with one or more drugs selected from 2-methyl-1-phenylpropan-2-amine, 2,3,4,5-bis-(gemdimethyl-methylenedioxy)-β

-D-fructopyranose sulfamate, naltrexone and bupropion.

16. The method of claim 13 wherein the compound of claim 1 or a pharmaceutically acceptable salt thereof, is administered with one or more drugs selected from the group consisting of pimavanserin, levodopa, carbidopa, pramipexol, ropinirole and bromocriptine.

17. The method of claim 3 wherein the disease or disorder is hot flashes due to menopause.

18. The method of claim 17 wherein the compound of claim 1 or a pharmaceutically acceptable salt thereof, is administered with a selective serotonin reuptake inhibitors (SSRI) selected from the group consisting of dapoxetine, fluoxetine, paroxetine, sertraline, citalopram, (S)-citalopram and bupropion.

19. The method of claim 3 wherein the disease or disorder is of anxiety disorders, General Anxiety Disorder (GAD), Panic Disorder (PD), Post-Traumatic Stress Disorder (PTSD), Social Phobia (SP), Health Anxiety (Hypochondriasis), depression, major depressive disorders, unipolar depression, bipolar I depression disorder, bipolar II depression disorder, treatment-resistant depression, single episodic and recurrent major depressive disorders, depression in the medically ill.

20. The method of claim 19 wherein the compound of claim 1, or a pharmaceutically acceptable salt thereof, is administered with a drug selected from vilazodone, samidorphan, buprenorphine, aripiprazole, and selective serotonin reuptake inhibitors (SSRI) selected from the group consisting of dapoxetine, fluoxetine, paroxetine, sertraline, citalopram, (S)-citalopram and bupropion.