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.

BENZOQUINOLONE INHIBITORS OF VMAT2

The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof. 2. The long acting pharmaceutical formulation of claim 1 , further comprising a polymeric material claim 1 , a hydrophobic material claim 1 , or an ion exchange resin.3. The long acting pharmaceutical formulation of claim 1 , comprising the salt of the compound.4. The long acting pharmaceutical formulation of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 50%.5. The long acting pharmaceutical formulation of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 90%.6. The long acting pharmaceutical formulation of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 98%.7. The long acting pharmaceutical formulation of claim 1 , in the form of a depot.8. The long acting pharmaceutical formulation of claim 1 , in the form of an emulsion.9. The long acting pharmaceutical formulation of claim 1 , comprising from 5 mg to 500 mg of the compound.10. A method of treating a VMAT2-mediated disorder in a patient in need of treatment comprising administering to the patient a long acting pharmaceutical formulation of .11. The method of claim 10 , wherein the disorder is a chronic hyperkinetic movement disorder claim 10 , Huntington's disease claim 10 , hemiballismus claim 10 , senile chorea claim 10 , a tic disorder claim 10 , tardive dyskinesia claim 10 , dystonia claim 10 , Tourette's syndrome claim 10 , depression claim 10 , cancer claim 10 , rheumatoid arthritis claim 10 , psychosis claim 10 , multiple sclerosis claim 10 , or asthma.12. The method of claim 11 , wherein the disorder is a chronic hyperkinetic movement disorder.13. The method of claim 12 , wherein the chronic hyperkinetic movement disorder is Huntington's disease.14. The method of claim 12 , wherein the chronic hyperkinetic movement disorder is ...

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.

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. The method as recited in further comprising the administration of an additional therapeutic agent.3. The method as recited in wherein the additional therapeutic agent is olanzapine or pimozide.4. The method as recited in wherein the additional therapeutic agent is a benzodiazepine or an antipsychotic.5. The method as recited in wherein the benzodiazepine is alprazolam claim 4 , adinazolam claim 4 , bromazepam claim 4 , camazepam claim 4 , clobazam claim 4 , clonazepam claim 4 , clotiazepam claim 4 , cloxazolam claim 4 , diazepam claim 4 , ethyl loflazepate claim 4 , estizolam claim 4 , fludiazepam claim 4 , flunitrazepam claim 4 , halazepam claim 4 , ketazolam claim 4 , lorazepam claim 4 , medazepam claim 4 , dazolam claim 4 , nitrazepam claim 4 , nordazepam claim 4 , oxazepam claim 4 , potassium clorazepate claim 4 , pinazepam claim 4 , prazepam claim 4 , tofisopam claim 4 , triazolam claim 4 , temazepam claim 4 , or chlordiazepoxide.6. The method as recited in wherein the antipsychotic is chlorpromazine claim 4 , levomepromazine claim 4 , promazine claim 4 , acepromazine claim 4 , triflupromazine claim 4 , cyamemazine claim 4 , chlorproethazine claim 4 , dixyrazine claim 4 , fluphenazine claim 4 , perphenazine claim 4 , prochlorperazine claim 4 , thiopropazate claim 4 , trifluoperazine claim 4 , acetophenazine claim 4 , thioproperazine claim 4 , butaperazine claim 4 , perazine claim 4 , periciazine claim 4 , thioridazine claim 4 , mesoridazine claim 4 , pipotiazine claim 4 , haloperidol claim 4 , trifluperidol claim 4 , melperone claim 4 , moperone claim 4 , pipamperone claim 4 , bromperidol claim 4 , benperidol claim 4 , droperidol claim 4 , fluanisone claim 4 , oxypertine claim 4 , molindone claim 4 , sertindole claim 4 , ziprasidone claim 4 , flupentixol claim 4 , clopenthixol claim 4 , ...

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. The method of claim 1 , wherein the metabolite is a deleterious metabolite.3. The method of claim 1 , wherein the half-life of the compound is increased claim 1 , as compared to the half-life of the corresponding non-deuterium enriched compound.4. The method of claim 1 , wherein the half-life of the compound is increased by at least 5% claim 1 , as compared to the half-life of the corresponding non-deuterium enriched compound.5. The method of claim 1 , comprising administering to the subject a mixture of diastereomers of the compound.6. The method of claim 1 , comprising administering to the subject a single diastereomer of the compound.7. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than about 1%.8. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than about 5%.9. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than about 10%.10. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than about 20%.11. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than about 50%.12. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than about 70%.13. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than about 90%.14. The method of claim 1 , wherein each position designed as D has deuterium enrichment of no less than 98%.15. The method of claim 1 , wherein said VMAT2-mediated disorder is a chronic hyperkinetic movement disorder.16. The method of claim 15 , wherein said chronic hyperkinetic movement disorder is Huntington's disease.17. The method of claim 15 , wherein said chronic ...

SUBSTITUTED PYRROLO[2,3-D]PYRIMIDINES

This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , characterized by one or more of the following features;(a) X is —O—;{'sub': '2', '(b) Y is —O— or —CH—;'}{'sup': '3a', '(c) Ris —OH;'}{'sup': 3b', '3d, 'sub': '1-4', '(d) Rand Rare each independently hydrogen or Caliphatic;'}{'sup': 3c', '5, '(e) Ris hydrogen, fluoro, or —OR;'}{'sup': 5', '5′, '(f) Rand Rare each hydrogen;'}{'sup': '4', '(g) each Ris hydrogen;'}{'sup': '2', '(h) each Ris hydrogen;'}{'sup': 'h', '(i) Ris hydrogen;'}{'sup': 'j', '(j) Ris hydrogen; and'}{'sup': 'k', 'sub': '1-4', '(k) Ris hydrogen, halo, or Caliphatic.'}4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , characterized by one or more of the features (a) through (f):{'sup': '3a', 'sub': 1-4', '1-4, '(a) Ris hydrogen, hydroxy, methoxy, Caliphatic, Cfluoroaliphatic, or fluoro;'}{'sup': '3b', '(b) Ris hydrogen;'}{'sup': '3c', '(c) Ris hydrogen or hydroxy;'}{'sup': '3d', '(d) Ris hydrogen;'}{'sup': '4', '(e) each Ris hydrogen; and'}{'sup': '5', '(f) Ris hydrogen.'}9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein Ring B is a phenyl ring substituted with 0-2 substituents independently selected from the group halo claim 8 , —OH claim 8 , -—O(Calkyl) claim 8 , —CN claim 8 , —N(R) claim 8 , —C(O)(Calkyl) claim 8 , —COH claim 8 , —CO(Calkyl) claim 8 , —C(O)NH claim 8 , —C(O)NH(Calkyl) claim 8 , —Caliphatic claim 8 , —Cfluoroaliphatic claim 8 , —O(Cfluoroaliphatic) claim 8 , optionally substituted aryl claim 8 , and optionally substituted heteroaryl.10. The compound of ...

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 115-. (canceled)17. (canceled)18. (canceled)19. The method as recited in further comprising the administration of an additional therapeutic agent.20. The method as recited in wherein said additional therapeutic agent is selected from the group consisting of olanzapine and pimozide.21. The method as recited in wherein said additional therapeutic agent is selected from the group consisting of benzodiazepines claim 19 , and antipsychotics.22. The method as recited in wherein said benzodiazepine is selected from the group consisting of alprazolam claim 21 , adinazolam claim 21 , bromazepam claim 21 , camazepam claim 21 , clobazam claim 21 , clonazepam claim 21 , clotiazepam claim 21 , cloxazolam claim 21 , diazepam claim 21 , ethyl loflazepate claim 21 , estizolam claim 21 , fludiazepam claim 21 , flunitrazepam claim 21 , halazepam claim 21 , ketazolam claim 21 , lorazepam claim 21 , medazepam claim 21 , dazolam claim 21 , nitrazepam claim 21 , nordazepam claim 21 , oxazepam claim 21 , potassium clorazepate claim 21 , pinazepam claim 21 , prazepam claim 21 , tofisopam claim 21 , triazolam claim 21 , temazepam claim 21 , and chlordiazepoxide.23. The method as recited in wherein said antipsychotic is selected from the group consisting of chlorpromazine claim 21 , levomepromazine claim 21 , promazine claim 21 , acepromazine claim 21 , triflupromazine claim 21 , cyamemazine claim 21 , chlorproethazine claim 21 , dixyrazine claim 21 , fluphenazine claim 21 , perphenazine claim 21 , prochlorperazine claim 21 , thiopropazate claim 21 , trifluoperazine claim 21 , acetophenazine claim 21 , thioproperazine claim 21 , butaperazine claim 21 , perazine claim 21 , periciazine claim 21 , thioridazine claim 21 , mesoridazine claim 21 , pipotiazine claim 21 , haloperidol claim 21 , trifluperidol claim 21 , melperone ...

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. 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 therapeutically effective amount of a compound according to and a pharmaceutically acceptable carrier.10. The pharmaceutical composition of claim 9 , formulated for oral claim 9 , parenteral claim 9 , or intravenous infusion administration.11. The pharmaceutical composition of claim 9 , formulated as a tablet or a capsule.12. The pharmaceutical composition of claim 9 , wherein said therapeutically effective amount is about 0.5 milligram to about 400 milligram total daily.13. A method of treating a mammal ...

Substituted N-aryl pyridinones

Disclosed herein are substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

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.

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. The compound of claim 1 , wherein each position indicated as D has deuterium enrichment of no less than about 90%.3. The compound of claim 1 , wherein each position indicated as D has deuterium enrichment of no less than about 98%.6. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier.7. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier.8. A method of treating a VMAT2-mediated disorder in a subject comprising administering to the subject a compound of .9. The method of claim 8 , wherein the VMAT2-mediated disorder is a chronic hyperkinetic movement disorder.10. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is Huntington's disease.11. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is chorea related to Huntington's disease.12. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is Tardive dyskinesia.13. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is Tourette's syndrome.14. The method of claim 8 , wherein the subject is human.15. The method of claim 8 , further resulting in at least one effect selected from the group consisting of:a. decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;b. increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;c. decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;d. increased average plasma levels of at least one metabolite of said compound per dosage unit ...

BENZOQUINOLONE INHIBITORS OF VMAT2

The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof. 2. The compound of claim 1 , wherein said compound is the alpha stereoisomer.3. The compound of claim 1 , wherein said compound is the beta stereoisomer.4. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 10%.5. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 50%.6. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 90%.7. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 98%.10. The compound of claim 9 , wherein said compound is the alpha stereoisomer.11. The compound of claim 9 , wherein said compound is the beta stereoisomer.12. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 10%.13. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 50%.14. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 90%.15. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 98%.19. The compound of claim 18 , wherein said compound is the alpha stereoisomer.20. The compound of claim 18 , wherein said compound is the beta stereoisomer.23. The method as recited in wherein said disorder is selected from the group consisting of chronic hyperkinetic movment disorders claim 22 , Huntington's disease claim 22 , hemiballismus claim 22 , senile chorea claim 22 , tic disorders claim 22 , tardive dyskinesia claim 22 , dystonia claim 22 , Tourette's syndrome claim 22 , depression claim 22 , cancer claim 22 , rheumatoid arthritis claim 22 , psychosis claim 22 , ...

Benzoquinoline inhibitors of vesicular monoamine transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

SUBSTITUTED PYRROLO]2,3-D]PYRIMIDINES

The present disclosure relates to compounds of formula (I-A) using the compounds 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , characterized by one or more of the following features:(a) X is —O—;{'sub': '2', '(b) Y is —O— or —CH—;'}{'sup': '3a', '(c) Ris —OH;'}{'sup': 3b', '3, 'sub': '1-4', '(d) Rand Rare each independently hydrogen or Caliphatic;'}{'sup': 3', '5, '(e) Ris hydrogen, fluoro, or —OR;'}{'sup': 5', '5′, '(f) Rand Rare each hydrogen;'}{'sup': '4', '(g) each Ris hydrogen;'}{'sup': '2', '(h) each Ris hydrogen;'}{'sup': 'h', '(i) Ris hydrogen;'}{'sup': 'j', '(j) Ris hydrogen; and'}{'sup': 'k', 'sub': '1-4', '(k) Ris hydrogen, halo, or Caliphatic.'}4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , characterized by one or more of the features (a) through (f):{'sup': '3a', 'sub': 1-4', '1-4, '(a) Ris hydrogen, hydroxy, methoxy, Caliphatic, Cfluoroaliphatic, or fluoro;'}{'sup': '3', '(b) Ris hydrogen;'}{'sup': '3', '(c) Ris hydrogen or hydroxy;'}{'sup': '3d', '(d) Ris hydrogen;'}{'sup': '4', '(e) each Ris hydrogen; and'}{'sup': '5', '(f) Ris hydrogen.'}9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein Ring B is a phenyl ring substituted with 0-2 substituents independently selected from the group halo claim 8 , —OH claim 8 , —O(Calkyl) claim 8 , —CN claim 8 , —N(R) claim 8 , —C(O)(Calkyl) claim 8 , —COH claim 8 , —CO(Calkyl) claim 8 , —C(O)N H claim 8 , —C(O)NH(Calkyl) claim 8 , —Caliphatic claim 8 , —Cfluoroaliphatic claim 8 , —O(Cfluoroaliphatic) claim 8 , optionally substituted aryl claim 8 , and optionally substituted heteroaryl.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 1', '12a', '12b', '12a', '12b', '12a', '12d, 'sub': '1-10', 'Ris Caliphatic, —Z—R, —Z—R, -L-Z—R, -L-Z—R, -L-Ror -L-R;'}{'sup': 13', '3, 'L is —C(R)═C(R)— or —C≡C—; and'}{'sup': 12d', '15', '15', '16', '14', '14', '16, ...

BENZOQUINOLONE INHIBITORS OF VMAT2

The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof. 2. The long acting pharmaceutical formulation of claim 1 , comprising the salt of the compound.3. The long acting pharmaceutical formulation of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 50%.4. The long acting pharmaceutical formulation of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 90%.5. The long acting pharmaceutical formulation of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 98%.6. The long acting pharmaceutical formulation of claim 1 , wherein the depot preparation is in the form of an emulsion.7. The long acting pharmaceutical formulation of claim 1 , comprising from 5 mg to 500 mg of the compound.8. A method of treating a VMAT2-mediated disorder in a patient in need of treatment comprising administering to the patient a long acting pharmaceutical formulation of .9. The method of claim 8 , wherein the disorder is a chronic hyperkinetic movement disorder claim 8 , Huntington's disease claim 8 , hemiballismus claim 8 , senile chorea claim 8 , a tic disorder claim 8 , tardive dyskinesia claim 8 , dystonia claim 8 , Tourette's syndrome claim 8 , depression claim 8 , cancer claim 8 , rheumatoid arthritis claim 8 , psychosis claim 8 , multiple sclerosis claim 8 , or asthma.10. The method of claim 9 , wherein the disorder is a chronic hyperkinetic movement disorder.11. The method of claim 10 , wherein the chronic hyperkinetic movement disorder is Huntington's disease.12. The method of claim 10 , wherein the chronic hyperkinetic movement disorder is tardive dyskinesia.13. The method of claim 10 , wherein the chronic hyperkinetic movement disorder is Tourette's syndrome.14. The method of claim 8 , wherein the administration is via implantation.15. The method of claim 14 , wherein ...

SUBSTITUTED N-ARYL PYRIDINONES

Disclosed herein are substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof. 2. The compound as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 98%.3. The compound as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 90%.4. The compound as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 50%.5. The compound as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 10%.7. The compound as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 98%.8. The compound as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 90%.9. The compound as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 50%.10. The compound as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 10%.12. A pharmaceutical composition as recited in claim 11 , further comprising one or more release-controlling excipients.13. The pharmaceutical composition as recited in claim 11 , further comprising one or more non-release controlling excipients ...

BENZOQUINOLINE INHIBITORS OF VMAT 2

The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof. 2. The compound of claim 1 , wherein said compound is the alpha stereoisomer.3. The compound of claim 1 , wherein said compound is the beta stereoisomer.4. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 10%.5. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 50%.6. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 90%.7. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 98%.10. The compound of claim 9 , wherein said compound is the alpha stereoisomer.11. The compound of claim 9 , wherein said compound is the beta stereoisomer.12. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 10%.13. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 50%.14. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 90%.15. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 98%.19. The compound of claim 18 , wherein said compound is the alpha stereoisomer.20. The compound of claim 18 , wherein said compound is the beta stereoisomer.21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier together with a compound as recited in claim 1 , or a salt or stereoisomer thereof.22. A method of treatment of a VMAT2-mediated disorder comprising the administration claim 1 , to a patient in need thereof claim 1 , of a therapeutically effective amount of a compound as recited in claim 1 , or a salt or stereoisomer thereof.23. The method ...

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. 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 and a pharmaceutically acceptable carrier.10. A method of treating a disease or condition involving monoamine reuptake claim 1 , comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound of .11. The method of claim 10 , wherein the disease or condition is an anxiety disorder claim 10 , generalized anxiety disorder claim 10 , depression claim 10 , post-traumatic stress disorder claim 10 , obsessive-compulsive disorder claim 10 , panic ...

Inhibitors of E1 activating enzymes

This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

BENZOQUINOLINE INHIBITORS OF VMAT 2

The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof. 2. The compound of claim 1 , wherein said compound is the alpha stereoisomer.3. The compound of claim 1 , wherein said compound is the beta stereoisomer.4. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 10%.5. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 50%.6. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 90%.7. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 98%.915-. (canceled)1920-. (canceled)23. The method as recited in wherein said disorder is selected from the group consisting of chronic hyperkinetic movment disorders claim 22 , Huntington's disease claim 22 , hemiballismus claim 22 , senile chorea claim 22 , tic disorders claim 22 , tardive dyskinesia claim 22 , dystonia claim 22 , Tourette's syndrome claim 22 , depression claim 22 , cancer claim 22 , rheumatoid arthritis claim 22 , psychosis claim 22 , multiple sclerosis claim 22 , and asthma.2428-. (canceled)29. The method as recited in claim 22 , further resulting in at least one effect selected from the group consisting of:a. decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;b. increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;c. decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;d. increased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched ...

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier. This application is a continuation of U.S. patent application Ser. No. 13/934,960, filed Jul. 3, 2013, which claims the benefit of U.S. patent application Ser. No. 12/562,621, filed Sep. 18, 2009, which claims the benefit of priority of U.S. provisional application No. 61/097,896, filed Sep. 18, 2008, the disclosures of which are hereby incorporated by reference as if written herein in their entireties.Disclosed herein are new benzoquinoline compounds, pharmaceutical compositions made thereof, and methods to inhibit vesicular monoamine transporter 2 (VMAT2) activity in a subject are also provided for, for the treatment of chronic hyperkinetic movement disorders.Tetrabenazine (Nitoman, Xenazine, Ro 1-9569), 1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinoline, is a vesicular monoamine transporter 2 (VMAT2) inhibitor. Tetrabenazine is commonly prescribed for the treatment of Huntington's disease (Savani et al., 2007, 68(10), 797; and Kenney et al., 2006, 6(1), 7-17).In vivo, tetrabenazine is rapidly and extensively metabolized to its reduced form, 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, which then binds specifically to VMAT2 (Zhang et al., 2006, 8(4), E682-692). Additional metabolic pathways involve O-demethylation of the methoxy groups, as well as hydroxylation of the isobutyl group (Schwartz et al., 1966, 15, 645-655). Adverse effects associated with the administration of tetrabenazine include neuroleptic malignant syndrome, drowsiness, fatigue, nervousness, anxiety, insomnia, agitation, confusion, orthostatic hypotension, nausea, dizziness, depression, and Parkinsonism.In order to eliminate foreign ...

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. 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%. This application is a continuation of U.S. patent application Ser. No. 15/205,491, filed Jul. 8, 2016, which is a continuation of U.S. patent application Ser. No. 12/234,236, filed Sep. 19, 2008, now U.S. Pat. No. 9,422,225, which is a continuation of U.S. patent application Ser. No. 11/565,451, filed Nov. 30, 2006, now U.S. Pat. No. 7,456,317 issued Nov. 25, 2008, which claims priority to U.S. Provisional Patent Application Nos. 60/741,315, filed Dec. 1, 2005 and 60/841,366, filed Aug. 30, 2006, all of which are incorporated by reference in their ...

SUBSTITUTED PYRROLO[2,3-D]PYRIMIDINES

This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia. 2. The compound of claim 1 , or a pharmaceuticals acceptable salt thereof characterized by one or more of the following features:(a) X is —O—;{'sub': '2', '(b) Y is —O—or —CH—;'}{'sup': '3a', '(c) Ris —OH;'}{'sup': 3b', '3d, 'sub': '1-4', '(d) Rand Rare each independently hydrogen or Caliphatic;'}{'sup': 3c', '5, '(e) Ris hydrogen, fluoro, or —OR;'}{'sup': 5', '5′, '(f) Rand R are each hydrogen;'}{'sup': '4', '(g) each Ris hydrogen;'}{'sup': '2', '(h) each Ris hydrogen;'}{'sup': 'h', '(i) Ris hydrogen;'}{'sup': 'j', '(j) Ris hydrogen; and'}{'sup': 'k', 'sub': '1-4', '(k) Ris hydrogen, halo, or Caliphatic.'}4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , characterized by one or more of the features (a) through (f):{'sup': '3a', 'sub': 1-4', '1-4, '(a) Ris selected from the group consisting of hydrogen, hydroxy, methoxy, Caliphatic, Cfluoroaliphatic, and fluoro;'}{'sup': '3b', '(b) Ris hydrogen;'}{'sup': '3c', '(c) Ris hydrogen or hydroxy;'}{'sup': '3d', '(d) Ris hydrogen;'}{'sup': '4', '(e) each Ris hydrogen; and'}{'sup': '5', '(f) Ris hydrogen.'}5. (canceled)6. (canceled)9. (canceled)10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris Caliphatic claim 1 , —Z—R claim 1 , —Z—R claim 1 , -L-Z—R claim 1 , -L-Z—R claim 1 , -L-Ror -L-R;{'sup': 13', '13, 'L is —C(R)═C(R)— or —C≡C—; and'}{'sup': 12d', '15', '15', '16', '14', '14', '16, 'sub': 2', '2', '2', '2', '2, 'Ris —NO, —CN, —S(O)R, —SOR, —SO—N(R), —COR, —C(O)R, or —C(O)N(R).'}11. (canceled)13. (canceled)15. The compound of claim 14 , or a pharmaceutically acceptable ...

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, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

Benzoquinoline Inhibitors of Vesicular Monoamine Transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 1. A compound of structural Formula I {'sub': 1', '27', '1', '27, 'R-Rare independently selected from the group consisting of hydrogen and deuterium; and at least one of R-Ris deuterium.'}, 'or a salt thereof, wherein This application is a continuation of U.S. patent application Ser. No. 17/314,279, filed May 7, 2021, which is a continuation of U.S. application Ser. No. 16/821,067, filed Mar. 17, 2020, which is a continuation of U.S. patent application Ser. No. 16/210,077, filed Dec. 5, 2018, which is a continuation of U.S. patent application Ser. No. 15/445,402, filed Feb. 28, 2017, which is a continuation of U.S. patent application Ser. No. 14/807,364, filed Jul. 23, 2015, which is a divisional of U.S. patent application Ser. No. 14/515,047, filed Oct. 15, 2014, which is a continuation of U.S. patent application Ser. No. 13/934,960, filed Jul. 3, 2013, which is a continuation of U.S. patent application Ser. No. 12/562,621, filed Sep. 18, 2009, which claims the benefit of priority of United States Provisional Application No. 61/097,896, filed Sep. 18, 2008, the disclosures of which are hereby incorporated by reference herein.Disclosed herein are new benzoquinoline compounds, pharmaceutical compositions made thereof, and methods to inhibit vesicular monoamine transporter 2 (VMAT2) activity in a subject are also provided for, for the treatment of chronic hyperkinetic movement disorders.Tetrabenazine (Nitoman, Xenazine, Ro 1-9569), 1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinoline, is a vesicular monoamine transporter 2 (VMAT2) inhibitor. Tetrabenazine is commonly prescribed for the treatment of Huntington's disease (Savani et al., 2007, 68(10), 797; and Kenney et al., 2006, 6(1), 7-17).In vivo, tetrabenazine is rapidly and extensively metabolized to its reduced form, ...

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. The composition as recited in wherein R-Reach have deuterium enrichment of no less than 50%.3. The composition as recited in wherein R-Reach have deuterium enrichment of no less than 90%.4. The composition as recited in wherein R-Reach have deuterium enrichment of no less than 98%.5. The method as recited in wherein said VMAT2-mediated disorder is a chronic hyperkinetic movement disorder.6. The method as recited in wherein said chronic hyperkinetic movement disorder is Huntington's disease.7. The method as recited in wherein said chronic hyperkinetic movement disorder is chorea related to Huntington's disease.9. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 50%.10. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 90%.11. The compound as recited in wherein each position represented as D has deuterium enrichment of no less than about 98%.12. The method as recited in wherein said VMAT2-mediated disorder is a chronic hyperkinetic movement disorder.13. The method as recited in wherein said chronic hyperkinetic movement disorder is Huntington's disease.14. The method as recited in wherein said chronic hyperkinetic movement disorder is chorea related to Huntington's disease. This application is a division of U.S. patent application Ser. No. 13/934,960, filed Jul. 3, 2013, which is a continuation of U.S. patent application Ser. No. 12/562,621, filed Sep. 18, 2009, issued as U.S. Pat. No. 8,524,733 on Sep. 3, 2013, which claims the benefit of priority of U.S. provisional application No. 61/097,896, filed Sep. 18, 2008, the disclosures of which are hereby incorporated by reference as if written herein in their entireties.Disclosed herein are new benzoquinoline compounds, ...

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. The composition as recited in wherein R-Reach have deuterium enrichment of no less than 50%.3. The composition as recited in wherein R-Reach have deuterium enrichment of no less than 90%.4. The composition as recited in wherein R-Reach have deuterium enrichment of no less than 98%.5. The pharmaceutical composition as recited in claim 1 , wherein said oral dosage form is a tablet or capsule.7. The pharmaceutical composition as recited in claim 6 , wherein said parenteral dosage form is formulated for intravenous dosage. This application is a continuation of U.S. patent application Ser. No. 13/934,960, filed Jul. 3, 2013, which is a continuation of U.S. patent application Ser. No. 12/562,621, filed Sep. 18, 2009, issued as U.S. Pat. No. 8,524,733 on Sep. 3, 2013, which claims the benefit of priority of U.S. provisional application No. 61/097,896, filed Sep. 18, 2008, the disclosures of which are hereby incorporated by reference as if written herein in their entireties.Disclosed herein are new benzoquinoline compounds, pharmaceutical compositions made thereof, and methods to inhibit vesicular monoamine transporter 2 (VMAT2) activity in a subject are also provided for, for the treatment of chronic hyperkinetic movement disorders.Tetrabenazine (Nitoman, Xenazine, Ro 1-9569), 1,3,4,6,7,11b-Hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[α]quinoline, is a vesicular monoamine transporter 2 (VMAT2) inhibitor. Tetrabenazine is commonly prescribed for the treatment of Huntington's disease (Savani et al., 2007, 68(10), 797; and Kenney et al., 2006, 6(1), 7-17).In vivo, tetrabenazine is rapidly and extensively metabolized to its reduced form, 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, which then binds specifically to VMAT2 (Zhang et al., 2006, 8(4), E682-692). ...

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, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described. 123-. (canceled)25. Polymorph Form B of d-1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl]-cyclohexanol hydrochloride (d-venlafaxine hydrochloride) as recited in claim 24 , wherein said polymorph exhibits high-intensity diffraction peaks at diffraction angles (2θ) of 6.683 claim 24 , 10.201 claim 24 , 13.441 claim 24 , 15.517 claim 24 , 18.198 claim 24 , 19.719 claim 24 , 20.258 claim 24 , 21.68 claim 24 , 22.658 claim 24 , 25.543 claim 24 , 28.022 claim 24 , and 35.02 in X-ray powder diffraction analysis.27164-. (canceled)165. A pharmaceutical composition comprising the compound as recited in and one or more pharmaceutically acceptable carriers.166. The pharmaceutical composition as recited in claim 165 , further comprising one or more release-controlling carriers.167. The pharmaceutical composition as recited in claim 165 , further comprising one or more non-release controlling carriers.168. The pharmaceutical composition as recited in claim 165 , wherein the composition is suitable for oral claim 165 , parenteral claim 165 , or intravenous infusion administration.169. The ...

Substituted n-aryl pyridinones

Disclosed herein are substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

Benzoquinoline inhibitors of vesicular monoamine transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

SUBSTITUTED PYRROLO]2,3-D]PYRIMIDINES

The present disclosure relates to compounds of formula (I-A) using the compounds

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, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

Substituted pyrrolo[2,3-d]pyrimidines

This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

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.

SUBSTITUTED N-ARYL PYRIDINONES

Disclosed herein are substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof. 2. The method as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 98%.3. The method as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 90%.4. The method as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 50%.5. The method as recited in claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rindependently has deuterium enrichment of no less than about 10%.7. The method as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 98%.8. The method as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 90%.9. The method as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 50%.10. The method as recited in claim 6 , wherein each of said positions represented as D has deuterium enrichment of at least 10%.11. The method as recited in claim 1 , wherein the fibrotic-meditated disorder claim 1 , the collagen-mediated disorder claim 1 , or the fibrotic-mediated and the collagen-mediated disorder is selected from the group consisting of idiopathic pulmonary fibrosis ...

SUBSTITUTED N-ARYL PYRIDINONES

Disclosed herein are substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof. 2. The composition as recited in claim 1 , wherein each of said positions represented as D has deuterium enrichment of at least 50%.3. The composition as recited in claim 1 , wherein each of said positions represented as D has deuterium enrichment of at least 90%.4. The composition as recited in claim 1 , wherein each of said positions represented as D has deuterium enrichment of at least 98%.5. The composition as recited in claim 1 , wherein said composition is formulated as an solution or suspension.6. The composition as recited in claim 5 , wherein said suspension comprises particles having an average size of 50 micrometers or less.7. The composition as recited in claim 5 , wherein said suspension comprises particles having an average size of 10 micrometers or less.8. The composition as recited in claim 5 , wherein said solution or suspension comprises ethanol claim 5 , water claim 5 , or mixtures thereof.9. The composition as recited in claim 5 , wherein said solution or suspension comprises an agent for dispersing claim 5 , solubilizing claim 5 , or extending release of the active ingredient.10. The composition as recited in claim 5 , wherein said solution or suspension comprises a surfactant selected from the group consisting of sorbitan trioleate claim 5 , oleic acid claim 5 , and an oligolactic acid.11. The composition as recited in claim 5 , wherein said solution or suspension is administered to a subject using a device selected from the group consisting of a pressurized container claim 5 , a pump claim 5 , a sprayer claim 5 , an atomizer claim 5 , and a nebulizer.12. The composition as recited in claim 11 , wherein said nebulizer is used in combination with a propellant.13. The composition as recited in claim 12 , wherein said propellant ...

Benzoquinoline inhibitors of vesicular monoamine transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

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.

Benzoquinoline inhibitors of vesicular monoamine transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Benzoquinoline Inhibitors of Vesicular Monoamine Transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. The compound of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 20%.3. The compound of claim 1 , wherein each position represented as D has deuterium enrichment of no less than about 50%.4. A pharmaceutical composition comprising the compound of together with a pharmaceutically acceptable carrier.5. The pharmaceutical composition of claim 4 , wherein each position represented as D in the compound has deuterium enrichment of no less than about 20%.6. The pharmaceutical composition of claim 4 , wherein each position represented as D in the compound has deuterium enrichment of no less than about 50%.7. A method of treating a hyperkinetic movement disorder in a human subject comprising administering to the subject the compound of .8. The method of claim 7 , wherein each position represented as D in the compound has deuterium enrichment of no less than about 20%.9. The method of claim 7 , wherein each position represented as D in the compound has deuterium enrichment of no less than about 50%.10. The method of claim 7 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease.11. The method of claim 7 , wherein the hyperkinetic movement disorder is Tardive dyskinesia.12. The method of claim 11 , wherein the subject is an adult human.13. The method of claim 8 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease.14. The method of claim 8 , wherein the hyperkinetic movement disorder is Tardive dyskinesia.15. The method of claim 14 , wherein the subject is an adult human.16. The method of claim 9 , wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease.17. The method of claim 9 , wherein the hyperkinetic movement disorder is Tardive dyskinesia.18. ...

BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof. 2. The compound of claim 1 , wherein each position indicated as D has deuterium enrichment of no less than about 90%.3. The compound of claim 1 , wherein each position indicated as D has deuterium enrichment of no less than about 98%.6. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier.7. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier.8. A method of treating a VMAT2-mediated disorder in a subject comprising administering to the subject a compound of .9. The method of claim 8 , wherein the VMAT2-mediated disorder is a chronic hyperkinetic movement disorder.10. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is Huntington's disease.11. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is chorea related to Huntington's disease.12. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is Tardive dyskinesia.13. The method of claim 9 , wherein the chronic hyperkinetic movement disorder is Tourette's syndrome.14. The method of claim 8 , wherein the subject is human.15. The method of claim 8 , further resulting in at least one effect selected from the group consisting of:a. decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;b. increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;c. decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;d. increased average plasma levels of at least one metabolite of said compound per dosage unit ...

Substituted indoles

Disclosed herein are substituted indoles of Formula (I), processes of preparation there of, pharmaceutical compositions thereof, and methods of their use there of.

Preparation and utility of substituted allylamines

Disclosed herein are substituted allylamines having structural Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and the methods of their use thereof. (I)

D9-Deuterated Venlafaxine

Polimorfo de la sal de clorhidrato del clorhidrato de d9-1-[2-dimetilamino-1-(4-metoxifenil)-etil]-ciclohexanol que tiene la fórmula estructural:**Fórmula** en el que dicho polimorfo presenta picos de difracción de alta intensidad a ángulos de difracción (2q) de 6,683, 10,201, 13,441, 15,517, 18,198, 19,719, 20,258, 21,68, 22,658, 25,543, 28,022 y 35,02 en análisis de difracción de rayos X de polvo. Polymorph of the hydrochloride salt of d9-1- [2-dimethylamino-1- (4-methoxyphenyl) -ethyl] -cyclohexanol hydrochloride having the structural formula: ** Formula ** in which said polymorph has diffraction peaks High intensity at diffraction angles (2q) of 6,683, 10,201, 13,441, 15,517, 18,198, 19,719, 20,258, 21.68, 22,658, 25,543, 28,022 and 35.02 in powder X-ray diffraction analysis.

Salts of a isothiazole-4-carboxamide and their useas anti-hyperproliferation agents.

The invention relates to hydrochloride, hydrobromide, hemi-citrate, acetate, p-tosylate, L-tartrate, hemi-succinate, and mesylate salt forms of 3-(4-bromo-2.6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide having the following formula: formula 1. The invention also relates to pharmaceutical compositions containing the hydrochloride, hydrobromide, hemi-citrate, acetate, p-tosylate, L-tartrate, hemi-succinate, and mesylate salts of formula 1. The invention further relates to methods of treating hyperproliferative diseases, such as cancers, in mammals, especially humans by administering the above salts and to methods of preparing the crystal forms of the above slats.

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, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

Methods of reduction of interpatient variability

Disclosed herein are methods for the reduction of inter-patient variability of a drug, such as in one or more parameters including half- life (t1/2), maximum plasma concentration (C max), time at maximal plasma concentration (T max), area under the time-versus-concentration curve (AUC). Also provided are methods of reducing side effects associated with drugs.

Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents

Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents

The invention relates to hydrochloride, hydrobromide, hemi-citrate, acetate, p- tosylate, L-tartrate, hemi-succinate, and mesylate salt forms of 3-(4-bromo- 2.6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4 - carboxylic acid amide having the following formula: formula 1. The invention also relates to pharmaceutical compositions containing the hydrochloride, hydrobromide, hemi-citrate, acetate, p-tosylate, L-tartrate, hemi-succinate, and mesylate salts of formula 1. The invention further relates to methods of treating hyperproliferative diseases, such as cancers, in mammals, especiall y humans by administering the above salts and to methods of preparing the crystal forms of the above slats.

Benzoquinoline inhibitors of vesicular monoamine transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2(VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Preparation and utility of substituted quinazoline compounds with alpha-adrenergic blocking effects

The present disclosure is directed to modulators of alpha-adrenergic receptors and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the use of such compounds for the treatment and/or management of hypertension, cardiac failure, prostatitis, and benign prostatic hyperplasia, and any other condition in which it is beneficial to modulate an alpha-adrenergic receptor.

Phenylacetic acid inhibitors of cyclooxygenase

The present invention relates to new phenylacetic acid inhibitors of cyclooxygenase activity, pharmaceutical compositions thereof, and methods of use thereof.

Substituted ethanolamines

The present invention relates to new substituted ethanolamine adrenergic receptor modulators, pharmaceutical compositions thereof, and methods of use thereof.

Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity

Pyridine sulfonamide modulators of endothelin-a receptor

The present invention relates to new pyridine sulfonamide modulators of endothelin-A receptor, pharmaceutical compositions thereof, and methods of use thereof.

N-arylpyridinones substituted as fibrotic inhibitors

Un compuesto que tiene la fórmula estructural I: o su sal farmacéuticamente aceptable o su solvato, en la que: R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, y R11 se seleccionan independientemente del grupo que consiste en hidrógeno o deuterio; al menos uno de R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, y R11 es deuterio; y si R7, R8, R9, R10, y R11 son deuterio, entonces al menos uno de R1, R2, R3, R4, R5, y R6 es deuterio. A compound having structural formula I: or its pharmaceutically acceptable salt or solvate, in which: R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group that it consists of hydrogen or deuterium; at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 is deuterium; and if R7, R8, R9, R10, and R11 are deuterium, then at least one of R1, R2, R3, R4, R5, and R6 is deuterium.

Isothiazole derivatives useful as anticancer agents

The present invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X 1 , R 1 , R 2 and R 3 are as defined herein. The invention also relates to pharmaceutical compositions containing the above compounds and to methods treating hyperproliferative disorders in mammals by administering the above compounds.

Benzoquinolone inhibitors of vmat2

Arylpiperazine modulators of d2 receptors, 5-ht1a receptors, and/or 5-ht2a receptors

The present invention relates to new arylpiperazine modulators of D2 receptors, 5-HT1A receptors, and/or 5-HT2A receptors, pharmaceutical compositions thereof, and methods of use thereof.

DEUTERATED d9-VENLAFAXINE

Salts of an isothiazole-4-carboxamide and their use as an anti-hyperproliferative agent

Pyrrolidinyl modulators of nicotinic acetylcholine receptors

The present invention relates to new pyrrolidinyl modulating nicotinic acetylcholine receptor compounds, pharmaceutical compositions thereof, and methods of use thereof. (Formula I)

Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity

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.

Preparation and utility of substituted quinazoline compounds with alpha-adrenergic blocking effects

The present disclosure is directed to modulators of alpha-adrenergic receptors and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the use of such compounds for the treatment and/or management of hypertension, cardiac failure, prostatitis, and benign prostatic hyperplasia, and any other condition in which it is beneficial to modulate an alpha-adrenergic receptor.

Hydrobromide salt and hemisuccinate salt of an isothiazole-4-carboxamide and its use and preparation, and pharmaceutical composition

Substituted hydroxyphenylamine compounds

The present invention relates to new substituted hydroxyphenylamine based modulators of hormone and/or pigment levels, pharmaceutical compositions thereof, and methods of use thereof. Formula (I).

Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents

The invention relates to hydrochloride, hydrobromide, hemi-citrate, acetate, p-tosylate, L-tartrate, hemi-succinate, and mesylate salt forms of 3-(4-bromo-2.6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide having the following formula: formula 1. The invention also relates to pharmaceutical compositions containing the hydrochloride, hydrobromide, hemi-citrate, acetate, p-tosylate, L-tartrate, hemi-succinate, and mesylate salts of formula 1. The invention further relates to methods of treating hyperproliferative diseases, such as cancers, in mammals, especially humans by administering the above salts and to methods of preparing the crystal forms of the above slats.

Salts of a isothiazole-4-carboxamide and their use as anti-hyperproliferation agents

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, attention deficit hyperactivity disorder, fibromyalgia, irritable bowel syndrome, and/or premature ejaculation are described.

Substituted pde5 inhibitors

Provided herein are substituted PDE5 inhibitors of Formula (1), and processes of preparation and pharmaceutical compositions thereof. Also provided are methods of their use for the treatment and/or management of hypertension, erectile dysfunction, and/or the inability to maintain improved erectile function. The compounds are deuterated tadalafil derivatives.

Preparation and utility of opioid analgesics

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.

Trifluoromethylphenyl modulators of calcium-sensing receptor

The present invention relates to new trifluoromethylphenyl modulators of calcium-sensing receptor, pharmaceutical compositions thereof, and methods of use thereof.

Benzoquinoline inhibitors of vesicular monoamine transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Preparation and utility of substituted erythromycin analogs

The present disclosure is directed to novel macrolide antibiotics of Formula 1 and pharmaceutically acceptable salts and prodrugs thereof; and the chemical syntheses and medical uses of these novel macrolide antibiotics for the treatment and/or management of infections caused by various aerobic and anaerobic gram-positive and gram-negative microorganisms as well as various mycobacteria.

Substituted piperazines

Disclosed herein are substituted piperazine late Na+ channel modulators of Formula (I), process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

Pyrazole carboxamide inhibitors of factor xa

Preparation and utility of substituted carboxylic acid compounds

The present disclosure is directed to modulators of cyclooxygenase (COX) enzymes and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the medical use of such compounds for the treatment and/or management of the severity and duration of non-specific pain, tension-type pain, headache, migraine, lower back pain, sciatica, dental pain, muscular pain, pain associated with acute soft tissue injuries, bursitis, tendonitis, lumbago, periarthritis, tennis elbow, sprains, strains, muscular problems associated with sports injuries, muscular problems associated with accidents, period pain, primary dysmenorrhoea, acute sore throat pain, osteoarthritis, rheumatoid arthritis, cancer, any disorder requiring analgesic response, any disorder requiring anti- inflammatory response, any disorder requiring antipyretic response, any conditions mediated by cyclooxygenase, cystic fibrosis, dementia, Alzheimer's disease, and/or conditions mediated by levels of .beta.-amyloid are described.

Xanthine modulators of adenosine a1 receptor

The present invention relates to new xanthine modulators of adenosine A 1 receptors, pharmaceutical compositions thereof, and methods of use thereof.

Benzisoxazole modulators of d2 receptor and/or 5-ht2a receptor

The present invention relates to new benzisoxazole modulators of D2 receptors and/or 5-HT2A receptors, pharmaceutical compositions thereof, and methods of use thereof.

Oxepine modulators of h1 receptors and/or inhibitors of mast cell degranulation

The present invention relates to new oxepine modulators of H1 receptors and/or inhibitors of mast cell degranulation, pharmaceutical compositions thereof, and methods of use thereof.

Pyrrolidinyl modulators of nicotinic acetylcholine receptors

The present invention relates to new pyrrolidinyl modulating nicotinic acetylcholine receptor compounds, pharmaceutical compositions thereof, and methods of use thereof. (Formula I)

Preparation of deuterated venlafaxines

Processes for preparaing deuterated venlafaxines whcih can be used as inhibitors of the uptake of monoamine neurotransmitters.

Benzoquinolone inhibitors of VMAT2

Abstract. R20 R24 R25 R1i 0 R21 R22 R26 R4 Re R,6$ R23 t R7 R1 9 R2y R3 N R4 R29 R28 RaR1O R9 R R, 0 Fornula I The present invention relates to benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and method of use thereof.

Pyrrolidinone inhibitors of pde-4

The present invention relates to new pyrrolidinone inhibitors of PDE-4 activity, pharmaceutical compositions thereof, and methods of use thereof.

Deuterated aminoglycidyl compounds

Benzoquinolone inhibitors of VMAT2

The present invention relates to new benzoquinolone inhibitors of VMAT2, pharmaceutical compositions thereof, and methods of use thereof.Formula (I)

Pyrazole carboxamide inhibitors of factor xa

The present invention relates to new pyrazole carboxamide inhibitors of factor Xa, pharmaceutical compositions thereof, and methods of use thereof.

Preparation and utility of substituted erythromycin analogs

The present disclosure is directed to novel macrolide antibiotics of Formula (I) and pharmaceutically acceptable salts and prodrugs thereof; and the chemical syntheses and medical uses of these novel macrolide antibiotics for the treatment and/or management of infections caused by various aerobic and anaerobic gram-positive and gram-negative microorganisms as well as various mycobacteria.

FORMS OF ACID AMIDA SALT 3- (4-BROMO-2,6-DIFLUORO-BENCILOXI) -5- (3- (PIRROLIDIN-1-ILBUTIL) UREIDO) ISOTIAZOL-4-CARBOXILICO AND PRODUCTION METHODS

La invención se refiere a las formas de sal hidrocloruro, hidrobromuro, hemicitrato, acetato, p-tosilato, L-tartrato, hemisuccinato y mesilato de amida de ácido 3-(4-bromo-2,6-difluorobenciloxi)-5-(3-(4-pirrolidin-1-ilbutil)ureido)isotiazol-4-carboxilico que tiene la fórmula (I); la invención también se refiere a composiciones farmaceuticas que contienen las sales hidrocloruro, hemicitrato, acetato. P-tosilato, hemisuccinato y mesilato de formula (I). La invención se refiere además a métodos para tratar enfermedades hiperproliferativas, tales como cánceres en mamíferos, especialmente seres humanos, por administración de las sales anteriores, y a los métodos para preparar las formas cristalinas de las sales anteriores. The invention relates to the forms of hydrochloride, hydrobromide, hemicitrate, acetate, p-tosylate, L-tartrate, hemisuccinate and amide acid amide 3- (4-bromo-2,6-difluorobenzyloxy) -5- (3 - (4-pyrrolidin-1-ylbutyl) ureido) isothiazol-4-carboxylic having the formula (I); The invention also relates to pharmaceutical compositions containing the hydrochloride, hemicitrate, acetate salts. P-tosylate, hemisuccinate and mesylate of formula (I). The invention further relates to methods for treating hyperproliferative diseases, such as cancers in mammals, especially humans, by administration of the foregoing salts, and to methods for preparing the crystalline forms of the foregoing salts.

Preparation and utility of substituted imidazopyridine compounds with hypnotic effects

The present disclosure is directed to modulators of GABA A receptors and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the medical use of such compounds for the treatment and/or management of sleep disorders and/or for providing a patient in need with a hypnotic, anxiolytic or anti-convulsive effect are described.

Substituted hydroxyphenylamine compounds

The present invention relates to new substituted hydroxyphenylamine based modulators of hormone and/or pigment levels, pharmaceutical compositions thereof, and methods of use thereof. Formula (I).

Preparation and utility of substituted carboxylic acid compounds

Deuterated aminoglycidyl compounds

Provided herein are substituted aminoglycidyl compounds of Formula (1), processes of preparation, and pharmaceutical compositions thereof and methods of their use for treating, preventing, or ameliorating one or more symptoms of a social anxiety disorder, an anxiety disorder, hyperthyroidism, tremor, glaucoma, hypertension, coronary artery bypass graft, chronic stable angina, atrial arrhythmia, migraine, bleeding esophageal varices, hypertrophic subaortic stenosis, heart failure, post-myocardial infarction, decreased left ventricular function after recent myocardial infarction, and/or any disorder ameliorated by beta adrenergic receptor modulators.

Amide inhibitors of renin

The present invention relates to new amide inhibitors of renin, pharmaceutical compositions thereof, and methods of use thereof

Substituted PDE5 inhibitors

Provided herein are substituted PDE5 inhibitors of Formula 1, and processes of preparation and pharmaceutical compositions thereof. Also provided are methods of their use for the treatment and/or management of hypertension, erectile dysfunction, and/or the inability to maintain improved erectile function.

Substituted deuterium enriched thiophenes for the treatment of hypertension

Disclosed herein are substituted pyrimidine-based endothelin modulators of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

Substituted phenylpiperidines with serotoninergic activity and enhanced therapeutic properties

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.

Scopine modulators of muscarinic acetylcholine receptor

The present invention relates to new scopine modulators of muscarinic acetylcholine receptors, pharmaceutical compositions thereof, and methods of use thereof. (I)

Adamantane modulators of nmda receptor and/or 5ht3 receptor

The present invention relates to new adamantane modulators of NMDA receptors and/or 5HT3 receptors, pharmaceutical compositions thereof, and methods of use thereof.

Prop-2-yn-1-amine inhibitors of monoamine oxidase type b

The present invention relates to new prop-2-yn-1-amine inhibitors of monoamine oxidase type B activity, pharmaceutical compositions thereof, and methods of use thereof.

Substituted N-Aryl pyridinones as fibrotic inhibitors