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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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20-09-2012 дата публикации

Sphingosine kinase type 1 inhibitors, and processes for using same

Номер: US20120237448A9

Provided are novel compositions and analogs which are useful in a number of applications, indications and diseases, as well as for monitoring pharmakinetics and patient management. These compounds and analogs are applicable to treating tumors of the central nervous system, e.g., glioblastoma (GBM).

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14-03-2013 дата публикации

RADIOLABELED COMPOUNDS AND METHODS THEREOF

Номер: US20130064770A1
Принадлежит: GE HEALTHCARE LIMITED

The present invention relates to radiodiagnostic compounds, methods of making those compounds, and methods of use thereof as imaging agents for preferably a HA serotonin 5-HT1A receptor for use in PET or SPECT, preferably PET. Compositions comprising an imaging-effective amount of radiolabeled compounds are also disclosed. The present invention also relates to non-radiolabeled compounds, methods of making those compounds, and methods of use thereof to treat various neurological and/or psychiatric disorders. 2. The compound of claim 1 , wherein the compound is radiolabeled.3. The compound of claim 1 , wherein the compound is not radiolabeled.4. The compound of claim 1 , wherein the compound comprises an F or a C atom.5. The compound of claim 1 , wherein an F or an C atom is attached directly to Ar.6. The compound of claim 1 , wherein a —OCHF group or —OCHgroup is directly attached to Ar claim 1 , wherein n is 1 to 4 and m is 2 to 8 claim 1 , respectively.7. The compound of claim 1 , wherein an F or an C atom is attached directly to Z or to a suitable group on Z.8. The compound of claim 1 , wherein an F or an C atom is attached directly to Lor Lor to a suitable group on Lor L.11. A composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a physiologically acceptable carrier or vehicle.12. A method for imaging one or more 5-HTreceptors in a subject in vivo claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, '(a) administering to the subject an imaging-effective amount of a compound of , or a pharmaceutically acceptable salt thereof; and'}{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, '(b) detecting the radioactive emission of the radiolabel on the compound of , or salt thereof, following its administration to the subject.'}13. The method of claim 12 , wherein the radioactive emission is detected using PET or SPECT.14. The method of claim 12 , wherein the radioactive emission is ...

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16-05-2013 дата публикации

DIAMINE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE A4 HYDROLASE

Номер: US20130123243A1
Принадлежит:

This invention is directed to compounds of formula (I): 3. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, cyano, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each independently hydrogen or halo.'}4. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, optionally substituted phenyl, furanyl, thienyl, thiazolyl, or optionally substituted oxazolyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each hydrogen.'}6. A compound according to wherein R an optionally substituted heteroaryl.7. A compound according to wherein R is furanyl claim 6 , oxazoyl claim 6 , pyrazolyl claim 6 , pyridinyl claim 6 , triazolyl claim 6 , thiazolyl claim 6 , or benzothiazolyl claim 6 , each of which is optionally substituted.8. A compound according to wherein:{'sup': 2', '7', '5a', '5b', '5c, 'Rand R, together with the nitrogens to which they are attached and one of R, Rand R, form an optionally substituted 6- to 10-membered bridged N-heterocyclyl.'}10. A compound according to wherein:{'sup': 3', '12', '12', '12, 'Ris a direct bond, —O—, —R—O—, —O—R—, —O—R—O—, or an optionally substituted straight or branched alkylene chain;'}{'sup': 4', '12a, 'Ris a direct bond, —O—R— or an optionally substituted straight or branched alkylene chain;'}{'sup': 8', '13', '10', '13', '10', '13', '10', '11, 'Ris aralkyl optionally substituted with one or more substituents selected from the group consisting of —R—OR, —R—C(═O)ORand —R—C(═O)N(R)R;'}{'sup': 9', '10, 'each Ris independently alkyl, halo or —O—R;'}{'sup': '12', 'Ris an optionally substituted straight ...

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23-05-2013 дата публикации

DERIVATIVES OF AMINOINDANES, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS

Номер: US20130131034A1
Принадлежит: SANOFI

The instant invention relates to derivatives of formula (I) 5. A pharmaceutical composition comprising compound of claim 1 , or an addition salt of said compound to a pharmaceutically acceptable salt claim 1 , or an hydrate or solvate of said compound.6. The pharmaceutical composition according to further comprising at least one pharmaceutically acceptable excipient.7. A method of treating or preventing fibrotic disorders claim 5 , skeletal muscle dysfunction claim 5 , renal failure claim 5 , atherosclerosis claim 5 , heart failure claim 5 , cancer chronic obstructive pulmonary disease claim 5 , pain claim 5 , pulmonary hypertension claim 5 , ischemic stroke claim 5 , myocardial infarction claim 5 , inflammation or peripheral arterial occlusive disease in a patient in need thereof comprising administering to said patient a therapeutically effective amount of the pharmaceutical composition of .8. The method according to claim 7 , wherein said fibrotic disorder is focal segmental glomerulosclerosis.9. The method according to wherein said cancer is oesophageal cancer or breast cancer. The instant invention relates to derivatives of aminoindanes, to their preparation and to their application in therapeutics.Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 has been associated with fibrotic disorders, such as focal segmental glomerulosclerosis (a) Winn et al, 2005, 308, 1801-1804. b) Hsu et al., 2007, 1772, 928-936. c) Kriz, 2005, 11, 527-530. d) Winn et al, 2005, 17, 378-387), skeletal muscle dysfunction (Millay et al., 2009, 106, 19023-19028), renal failure, atherosclerosis, heart failure (Kuwahara et al., 2006, 116, 3114-26), cancer (e.g. oesophageal cancer, breast cancer) (a) Aydar et al., 2009, 9, 23. b) Cai et al., 2009, 125, 2281-2287. c) Shi et al., 2009, 58, 1443-1450), chronic obstructive pulmonary disease (Sel et al., 2008, 38, 1548-1558), pain (Alessandri-Haber ...

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30-05-2013 дата публикации

INDANE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF

Номер: US20130137746A1
Принадлежит: ARAGON PHARMACEUTICALS, INC.

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '1', 'sub': 1', '4, 'Ris C-Calkyl;'}{'sup': 2', '8, 'Ris H or R;'}{'sup': 3', '8, 'Ris R;'}or{'sup': 2', '3, 'Rand Rare taken together with the N atom to which they are attached to form a substituted or unsubstituted monocyclic heterocycloalkyl, a substituted or unsubstituted bicyclic heterocycloalkyl, a substituted or unsubstituted monocyclic heteroaryl, or a substituted or unsubstituted bicyclic heteroaryl;'}{'sup': '4', 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'each Ris independently selected from H, halogen, —CN, —OH, C-Calkyl, C-Cfluoroalkyl, C-Cfluoroalkoxy, C-Calkoxy, and C-Cheteroalkyl;'}{'sup': 5', '7', '7', '8', '8', '8, 'sub': 2', '2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'each Ris independently selected from H, halogen, —CN, —OH, —OR, —SR, —S(═O)R, —S(═O)R, —NHS(═O)R, C-Calkyl, C-Cfluoroalkyl, C-Cfluoroalkoxy, C-Calkoxy, and C-Cheteroalkyl;'}{'sup': '5', 'or two Ron adjacent carbon atoms are taken together with the carbon atoms to which they are attached to form a fused substituted or unsubstituted monocyclic heterocycle;'}{'sup': 6', '7', '7', '8', '8', '8, 'sub': 2', '2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'each Ris independently selected from H, halogen, —CN, —OH, —OR, —SR, —S(═O)R, —S(═O)R, —NHS(═O)R, C-Calkyl, C-Cfluoroalkyl, C-Cfluoroalkoxy, C-Calkoxy, and C-Cheteroalkyl;'}{'sup': '6', 'or two Ron adjacent carbon atoms are taken together with the carbon atoms to which they are attached to form a fused substituted or unsubstituted ...

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15-08-2013 дата публикации

CANNABIDINOID DERIVATIVES

Номер: US20130209483A1
Автор: McAllister Sean D.
Принадлежит: Sutter West Bay Hospitals

The disclosure relates to cannabinoid derivative compounds, pharmaceutical compositions made thereof, and methods for treating various diseases and disorders including cancer. 2. The compound of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , n-butyl claim 1 , n-pentyl claim 1 , n-hexyl claim 1 , n-heptyl claim 1 , isopropyl claim 1 , sec-butyl claim 1 , (1-methyl)butyl claim 1 , (1-methyl)pentyl claim 1 , (1-methyl)hexyl claim 1 , (1-methyl)heptyl claim 1 , (1 claim 1 ,1-dimethyl)propyl claim 1 , (1 claim 1 ,1-dimethyl)butyl claim 1 , (1 claim 1 ,1-dimethyl)pentyl claim 1 , (1 claim 1 ,1-dimethyl)hexyl claim 1 , (1 claim 1 ,1-dimethyl)heptyl claim 1 , (1 claim 1 ,2-dimethyl)propyl claim 1 , (1 claim 1 ,2-dimethyl)butyl claim 1 , (1 claim 1 ,2-dimethyl)pentyl claim 1 , (1 claim 1 ,2-dimethyl)hexyl claim 1 , (1 claim 1 ,2-dimethyl)heptyl claim 1 , (1 claim 1 ,3-dimethyl)butyl claim 1 , (1 claim 1 ,3-dimethyl)pentyl claim 1 , (1 claim 1 ,3-dimethyl)hexyl claim 1 , (1 claim 1 ,3-dimethyl)heptyl claim 1 , (1 claim 1 ,4-dimethyl)pentyl claim 1 , (1 claim 1 ,4-dimethyl)hexyl claim 1 , (1 claim 1 ,4-dimethyl)heptyl claim 1 , (1 claim 1 ,5-dimethyl)hexyl claim 1 , (1 claim 1 ,5-dimethyl)heptyl claim 1 , (1 claim 1 ,6-dimethyl)heptyl claim 1 , (1 claim 1 ,2-diethyl)butyl claim 1 , (1 claim 1 ,2-diethyl)pentyl claim 1 , (1 claim 1 ,2-diethyl)hexyl claim 1 , (1 claim 1 ,2-diethyl)heptyl claim 1 , (1 claim 1 ,2-diethyl)pentyl claim 1 , (1 claim 1 ,3-diethyl)pentyl claim 1 , (1 claim 1 ,3-diethyl)hexyl claim 1 , (1 claim 1 ,3-diethyl)heptyl claim 1 , (1 claim 1 ,4-diethyl)pentyl claim 1 , (1 claim 1 ,4-diethyl)hexyl claim 1 , (1 claim 1 ,4-diethyl)heptyl claim 1 , (1 claim 1 ,5-diethyl)hexyl claim 1 , (1 claim 1 ,5-diethyl)heptyl claim 1 , (1 claim 1 ,6-diethyl)heptyl claim 1 , (1 claim 1 ,2 claim 1 ,3-trimethyl)butyl claim 1 , (1 claim 1 ,1 claim 1 ,2-trimethyl)butyl claim 1 , (1 claim 1 ,1 claim 1 ,3-trimethyl) ...

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15-08-2013 дата публикации

APPLICATION OF 5-HT6 RECEPTOR ANTAGONISTS FOR THE ALLEVIATION OF COGNITIVE DEFICITS OF DOWN SYNDROME

Номер: US20130210829A1
Принадлежит:

Methods for treating Down syndrome and improving cognitive function of a patient with an intellectual disability are disclosed. 5-hydroxytryptamine sub-receptor six (5-HT) receptor antagonists are provided for improving the cognition of a Down syndrome patient. 1. A method of treating Down syndrome , comprising administering to a subject in need thereof an effective amount of a 5-HTreceptor antagonist.2. The method of claim 1 , where the 5-HTreceptor antagonist is chosen from: a 5-HTreceptor inverse agonist claim 1 , a 5-HTreceptor competitive antagonist claim 1 , or a 5-HTreceptor inhibitor.3. The method of claim 2 , wherein the 5-HTreceptor antagonist is a 5-HTreceptor competitive antagonist.4. The method of claim 1 , wherein the 5-HTreceptor antagonist directly binds to the 5-HTreceptor.5. The method of claim 1 , wherein the 5-HTreceptor antagonist is a small molecule 5-HTreceptor antagonist.6. The method of claim 5 , wherein the small molecule 5-HTreceptor antagonist has a molecular weight of less than 800 Daltons.9. The method of claim 1 , wherein the subject is administered a pharmaceutical composition comprising a 5-HTreceptor antagonist or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.10. The method of claim 1 , wherein the route of administration of the 5-HTantagonist is selected from at least one of the following: intravenous claim 1 , intraperitoneal claim 1 , subcutaneous claim 1 , parenteral claim 1 , intramuscular claim 1 , oral claim 1 , topical claim 1 , transmucosal claim 1 , intraventricular claim 1 , or intrathecal administration.11. The method of claim 1 , wherein the subject suffers from a comorbid disorder associated with Down syndrome comprising Autism spectrum disorders claim 1 , attention deficit hyperactivity disorder claim 1 , obsessive compulsive disorder claim 1 , and disorders involving speech and language.12. The method of claim 1 , wherein the 5-HTantagonist is administered in ...

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15-08-2013 дата публикации

PROCESS FOR THE MANUFACTURE OF TMHQ

Номер: US20130211080A1
Принадлежит: DSM IP ASSETS B.V.

The present invention is directed to a process for the manufacture of 2,3,5-trimethyl-hydro-p-benzoquinone comprising the following steps: a) hydrogenating 2,6-dimethyl-p-benzoquinone with hydrogen in the presence of a hydrogenation catalyst in an organic solvent to obtain 2,6-dimethyl-hydro-p-benzoquinone; b) reacting 2,6-dimethyl-hydro-p-benzoquinone with a secondary amine and formal-dehyde in an organic solvent to obtain 2,6-dimethyl-3-(N,N-disubstituted aminomethyl)-hydro-p-benzoquinone; c) reacting 2,6-dimethyl-3-(N,N-disubstituted aminomethyl)-hydro-p-benzoquinone with hydrogen in the presence of a hydrogenolysis catalyst in an organic solvent to obtain 2,3,5-trimethylhydro-p-benzoquinone; wherein the organic solvent in all steps a), b) and c) is independently selected from the group consisting of methyl tert.-butyl ether, ethyl tert.-butyl ether, tert.-amyl ether, methoxycyclopentane and any mixtures thereof. Preferably the organic solvent used in all steps a), b) and c) is the same. 1. A process for the manufacture of 2 ,3 ,5-trimethyl-hydro-p-benzoquinone comprising the following steps:a) hydrogenating 2,6-dimethyl-p-benzoquinone with hydrogen in the presence of a hydrogenation catalyst in an organic solvent to obtain 2,6-dimethyl-hydro-p-benzoquinone;b) reacting 2,6-dimethyl-hydro-p-benzoquinone with a secondary amine and formaldehyde in an organic solvent to obtain 2,6-dimethyl-3-(N,N-disubstituted aminomethyl)-hydro-p-benzoquinone;c) reacting 2,6-dimethyl-3-(N,N-disubstituted aminomethyl)-hydro-p-benzoquinone with hydrogen in the presence of a hydrogenolysis catalyst in an organic solvent to obtain 2,3,5-trimethylhydro-p-benzoquinone;wherein the organic solvent used in steps a), b) and c) is independently selected from the group consisting of methyl tert.-butyl ether, ethyl tert.-butyl ether, methyl tert.-amyl ether, methoxycyclopentane and any mixtures thereof.2. The process according to claim 1 , wherein the organic solvent in all steps a) claim 1 , b) ...

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05-09-2013 дата публикации

ROS-Activated Compounds as Selective Anti-Cancer Therapeutics

Номер: US20130230542A1
Принадлежит:

Provided are compounds according to the following Formula I: 2. The compound according to claim 1 , wherein said alkyl claim 1 , aryl claim 1 , and aralkyl substitutions are selected from the group consisting of alkoxyl claim 1 , halo claim 1 , OH claim 1 , CN claim 1 , carboxyl claim 1 , carboxyl ester claim 1 , and substituted or unsubstituted alkyl.3. The compound according to claim 1 , wherein Ris H or alkyl when Ris aryl or aralkyl claim 1 , and wherein Ris H or alkyl when Ris aryl or aralkyl.4. The compound according to claim 1 , wherein Rand Rare each independently selected from the group consisting of H claim 1 , substituted or unsubstituted C-Calkyl claim 1 , and substituted or unsubstituted phenyl; and Ris OH.5. The compound according to claim 1 , wherein the cancer is associated with production of elevated reactive oxygen species.6. The compound according to claim 5 , wherein the cancer is selected from the group consisting of leukemia claim 5 , renal cancer claim 5 , and cancers of the central nervous system.7. The compound according to claim 6 , wherein the leukemia is selected from the group consisting of acute myeloid leukemia claim 6 , acute lymphoblastic leukemia claim 6 , plasmacytoma claim 6 , myeloma claim 6 , myelogenous leukemia claim 6 , acute lymphocytic leukemia claim 6 , acute promyelocytic leukemia claim 6 , and multiple myeloma.9. A method of reducing proliferative capacity in a cell claim 1 , the method comprising contacting the cell with an effective amount of a compound according to .10. The method according to claim 9 , wherein the cell is a mammalian cell.11. The method according to claim 10 , wherein the cell is a cancer cell.12. A method of treating a cancer associated with elevated ROS comprising administering to a subject in need thereof an effective amount of a compound according to .13. The method according to claim 12 , wherein the subject is a mammal.14. The method according to claim 13 , wherein the cancer is selected from ...

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19-09-2013 дата публикации

BENZODIOXANE INHIBITORS OF LEUKOTRIENE PRODUCTION

Номер: US20130244996A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to compounds of formula (I): 5. A pharmaceutical composition comprising one or more compounds of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier or excipient.6. A pharmaceutical composition comprising one or more compounds of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , and a pharmaceutically acceptable carrier or excipient.7. A pharmaceutical composition comprising one or more compounds of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , and a pharmaceutically acceptable carrier or excipient.8. A pharmaceutical composition comprising one or more compounds of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , and a pharmaceutically acceptable carrier or excipient.9. The pharmaceutical composition of claim 1 , further comprising at least one additional pharmacologically active substance.10. A method of treating leukotriene-mediated disorders comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to a patient in need thereof.11. The method of claim 10 , wherein the leukotriene-mediated disorder is a cardiovascular disease.12. A method of treating leukotriene-mediated disorders comprising administering the pharmaceutically composition of claim 5 , to a patient in need thereof.13. The method of claim 12 , wherein the leukotriene-mediated disorder is a cardiovascular disease. This invention relates to benzodioxanes that are useful as inhibitors of leukotriene Ahydrolase (LTAH) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of leukotrienes including asthma, allergy and cardiovascular diseases including atherosclerosis, myocardial infarction and stroke. This invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds ...

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19-09-2013 дата публикации

ACRYLOMIDO DERIVATIVES USEFUL AS INHIBITORS OF THE MITOCHONDRIAL PERMEABILITY TRANSITION

Номер: US20130245019A1
Принадлежит: CONGENIA SRL

Acrylamido derivatives useful as therapeutic agents, particularly for the prevention and/or treatment of diseases and conditions associated with the activity of the mitochondrial permeability transition pore (MPTP), such as the diseases characterized by ischemia/reperfusion, oxidative or degenerative tissue damage, are herein described. These compounds belong to the structural formula (I) wherein R, R′, R″, W and a are as defined in the specification. The invention also relates to the preparation of these compounds, as well as to pharmaceutical compositions comprising them. 110-. (canceled)12. The method according to claim 11 , for the prevention and/or treatment of a diseases resulting from ischemia/reperfusion damage or oxidative damage claim 11 , age-related diseases claim 11 , degenerative and neurodegenerative diseases.13. The method according to claim 12 , for the prevention and/or treatment of acute myocardial infarction claim 12 , heart failure claim 12 , organ ischemia claim 12 , ischemic and traumatic brain damage claim 12 , Duchenne muscular dystrophy claim 12 , Uilrich congenital muscular dystrophy claim 12 , Bentham myopathy claim 12 , amyotrophic lateral sclerosis claim 12 , Huntington's disease claim 12 , Alzheimer's disease claim 12 , Parkinson's disease claim 12 , diabetes type I and type II claim 12 , diabetic complications claim 12 , hyperglycemic tissue damage claim 12 , hypoglycemic tissue damage claim 12 , cholestasis claim 12 , or alcohol-induced damage.1415-. (canceled) The present invention relates to acrylamido derivatives and to their use as therapeutic agents, particularly for the prevention and/or treatment of diseases and conditions associated with the activity of the mitochondrial permeability transition pore (MPTP), such as the diseases characterized by ischemia/reperfusion, oxidative or degenerative tissue damage. The invention also relates to the preparation of these compounds, as well as to pharmaceutical compositions comprising ...

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10-10-2013 дата публикации

TREATMENT OF MITOCHONDRIAL DISEASES

Номер: US20130267538A1
Принадлежит:

The invention relates the method of treatment or amelioration of mitochondrial disorders such as Alzheimer's disease, Parkinson's disease, Friedreich's ataxia (FRDA), cerebellar ataxias, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Myoclonic Epilepsy with Ragged Red Fibers (MERFF), amyotrophic lateral sclerosis (ALS), motor neuron diseases, Huntington's disease, macular degeneration, and epilepsy, with chroman derivatives of Formula I or Formula II as described herein. 2. The method of claim 1 , comprising administering to said subject a therapeutically effective amount of a compound of Formula I.3. The method of claim 2 , comprising administering the compound of Formula I wherein Ris hydrogen claim 2 , Calkyl claim 2 , or Calkenyl.4. The method of claim 2 , comprising administering the compound of Formula I wherein Rand Rare independently of each other Calkyl or halogen.5. The method of claim 4 , comprising administering the compound of Formula I wherein Ris Calkyl and Ris Calkyl.6. The method of claim 2 , comprising administering the compound of Formula I wherein Ris Calkyl claim 2 , and Ris Calkyl or Calkenyl.7. The method of claim 2 , comprising administering the compound of Formula I wherein Rand Rtaken together with the carbon to which they are attached form a 5-6 membered carbocyclic ring claim 2 , optionally substituted with Calkyl claim 2 , Calkoxy claim 2 , hydroxy claim 2 , carboxy claim 2 , carboxyalkyl claim 2 , alkoxycarbonyl claim 2 , alkoxycarbonylalkyl claim 2 , aminocarbonyl claim 2 , aminocarbonylalkyl claim 2 , or hydroxyalkyl.8. The method of claim 1 , comprising administering to said subject a therapeutically effective amount of a compound of Formula II.9. The method of claim 8 , comprising administering the compound of Formula II claim 8 , wherein Ris —COOH claim 8 , or —COORand Ris Calkyl.11. The method of claim 1 , comprising administering a therapeutically effective amount ...

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10-10-2013 дата публикации

N,N+hu 1 +l SUBSTITUTED PIPERAZINES HAVING COMBINED ANTIAGGREGANT, ANTICOAGULANT AND VASODILATORY ACTIVITY, AND METHOD FOR PRODUCING SAME

Номер: US20130267707A1

The invention relates to derivatives of N,N′-substituted piperazines of the general formula (I): 6. The method for synthesis of N claim 3 ,N′-substituted piperazines of claim 3 , wherein said carboxamidating agents are represented by: 1H-pyrazole-1-carboxamidine claim 3 , or dicyandiamide claim 3 , or salts thereof.7. The method for synthesis of N claim 3 ,N′-substituted piperazines of claim 3 , wherein said bases are represented by: alkaline metal hydroxides claim 3 , or carbonates claim 3 , or organic bases thereof.83. The method for synthesis of N claim 3 ,N′-substituted piperazines of claim claim 3 , wherein said organic solvents are represented by one of the following: lower aliphatic alcohols claim 3 , acetonitrile claim 3 , tetrahydrofurane claim 3 , dimethylformamide claim 3 , dimethylsulfoxide claim 3 , dichloromethane claim 3 , or mixtures thereof.13. The method for synthesis of said compounds of N claim 10 ,N′-substituted piperazines according to claim 10 , wherein said organic solvents are represented by one of the following: lower aliphatic alcohols claim 10 , acetonitrile claim 10 , tetrahydrofurane claim 10 , dimethylformamide claim 10 , dimethylsulfoxide claim 10 , dichloromethane claim 10 , chloroform claim 10 , or mixtures thereof used.14. The method for synthesis of said compounds of N claim 10 ,N′-substituted piperazines according to claim 10 , wherein said halogenalkylsulfonic acids or salts thereof are represented by: 2-bromoethanesulfonic acid claim 10 , 2-hydroxy-3-chloropropanesulfonic acid claim 10 , or sodium salts thereof.15. The method for synthesis of said compounds of N claim 10 ,N′-substituted piperazines according to claim 10 , wherein said bases are represented by: ammonia claim 10 , sodium hydroxide claim 10 , or potassium hydroxide claim 10 , or sodium carbonate claim 10 , or sodium hydrocarbonate claim 10 , or potassium carbonate claim 10 , or potassium hydrocarbonate.16. The compounds according to claim 1 , wherein said low ...

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31-10-2013 дата публикации

Amination of Aryl Alcohol Derivatives

Номер: US20130289270A1

Embodiments of the invention provide methods and materials for chemical cross-coupling reactions that utilize aryl alcohol derivatives as cross-coupling partners. Embodiments of the invention include methods for the amination of aryl sulfamates and carbamates, which are attractive cross-coupling partners, particularly for use in multistep synthesis. Illustrative embodiments include versatile means to use simple derivatives of phenol as precursors to polysubstituted aryl amines, as exemplified by a concise synthesis of the antibacterial drug linezolid. 1. A method for making a cross-coupled compound comprising: combining together:an aryl alcohol derivative, wherein the aryl alcohol derivative comprises an aryl carbamate compound or an aryl sulfamate compound;an amine; anda transition metal catalyst, wherein the transition metallic catalyst comprises nickel or palladium;wherein the aryl alcohol derivative, the amine and the transition metal catalyst are combined so as to allow a cross-coupling reaction between the amine, the aryl alcohol derivative and the transition metal catalyst that results in the formation of the cross-coupled compound that comprises a C—N bond between a carbon atom present in the aryl alcohol derivative and a nitrogen atom present in the amine, in a yield of at least 25%;so that the cross-coupled compound is made.2. The method of claim 1 , wherein the cross-coupling reaction results in the formation of the cross-coupled compound in a yield of at least 50%.3. The method of claim 1 , wherein the aryl alcohol derivative comprises an aryl sulfamate compound.4. The method of claim 1 , wherein the amine comprises a secondary amine.5. The method of claim 1 , wherein the aryl alcohol derivative comprises a heteroatom.6. The method of claim 1 , wherein the transition metallic catalyst comprises nickel.7. The method of claim 1 , wherein the transition metal catalyst comprises an air stable Ni(II) precatalyst complex prior to its combination with the amine ...

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26-12-2013 дата публикации

BENZODIOXANE INHIBITORS OF LEUKOTRIENE PRODUCTION

Номер: US20130345195A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to compounds of formula (I): 120-. (canceled)21. A compound selected from the group consisting of:1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]pyrrolidine;4-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]morpholine;1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-4,4-dimethylpiperidine;8-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-2,8-diazaspiro[4.5]decan-1-one;1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-4-fluoropiperidine;(1s,4s)-7-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-7-azabicyclo[2.2.1]heptane;4-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]thiomorpholine 1,1-dioxide;1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}-N,N-dimethylpiperidine-4-carboxamide;(3S)-1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]pyrrolidin-3-ol;1-({1-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]piperidin-3-yl}methyl)pyrrolidin-2-one;1-{4-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]piperazin-1-yl}ethanone;2-{[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]amino}-1-(pyrrolidin-1-yl)ethanone;N-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}-N-methyl-1-(methylsulfonyl)piperidin-4-amine;1-{4-[{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}(methyl)amino]piperidin-1-yl}ethanone;3-[4-(pyrrolidin-1-ylmethyl)phenyl]-2,3-dihydro[1,4]dioxino[2,3-b]pyridine;7-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine;3-{4-[(1,1-dioxidothiomorpholin-4-yl)methyl]phenyl}-2,3-dihydro[1,4]dioxino[2,3-b]pyridine;3-[4-(morpholin-4-ylmethyl)phenyl]-2,3-dihydro[1,4]dioxino[2,3-b]pyridine;(3R)-1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidine-3-carboxylic acid;(3S)-1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidine-3-carboxylic acid;1-(1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidin-4-yl)-2,2,2-trifluoroethanol;2-(1-{4-[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]benzyl}piperidin-4-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol;N-[4-(2,3-dihydro-1,4-benzodioxin-2-yl)benzyl]-2-methylpropan-2-amine;(2R)—N-[4-(2,3-dihydro-1, ...

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02-01-2014 дата публикации

CHROMENE DERIVATIVES

Номер: US20140005247A1

Derivates of chromene of formula I, where the meanings for the various substituents are as indicated in the description. These compounds are useful as inhibitors of TCR-Nck interaction in T lymphocytes. 2. The compound according to where each Rand Rindependently represent hydrogen claim 1 , Calkyl claim 1 , haloCalkyl claim 1 , Calkoxyl claim 1 , halogen or Cy.3. The compound according to where each Rindependently represents hydrogen claim 1 , Calkoxyl or Cy.4. The compound according to where each Rindependently represents Calkyl claim 1 , haloCalkyl or halogen claim 1 , preferably haloCalkyl or halogen.5. The compound according to where Rrepresents hydrogen.6. The compound according to where Cyrepresents a monocyclic heterocycle of 5 or 6 members claim 1 , saturated or partially unsaturated which is merged with the rest of the molecule by any available N atom claim 1 , where Cymay contain 1 or 2 heteroatoms selected from N claim 1 , O and S claim 1 , where one or more C or S atoms of the ring can be oxidized to form groups CO claim 1 , SO or SO claim 1 , and where Cyis optionally replaced by one or more R.9. The compound according to i where each Cyindependently represents phenyl or an aromatic ring of 5 or 6 members which can be joined to the rest of the molecule by any available C or N atom claim 1 , where Cycontains 1 or 2 heteroatoms selected from N claim 1 , O and S claim 1 , where one or more atoms of C or S of the ring may be oxidized to form CO claim 1 , SO or SOgroups claim 1 , and where Cyis optionally replaced by one or more R.10. The A compound according to any one of where each Rindependently represents Calkyl claim 1 , hydroxyl claim 1 , Calkoxyl claim 1 , haloCalkyl claim 1 , hydroxyCalkyl or halogen.11. The compound according to where n represents 0 or 1.12. The compound according to where m represents 1.16. A pharmaceutical composition comprising a compound of formula I according to or a pharmaceutically acceptable salt thereof and one or more ...

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30-01-2014 дата публикации

CHROMENE COMPOUND

Номер: US20140030529A1
Принадлежит: TOKUYAMA CORPORATION

A chromene compound which develops a color of a neutral tint and has high color optical density, high fading speed and excellent durability and a photochromic curable composition comprising the chromene compound and polymerizable monomers. 3. The chromene compound according to claim 1 , wherein in the above formula (2) claim 1 , Rand Rform an aliphatic hydrocarbon ring together with the 13-position carbon atom bonded thereto claim 1 , and the aliphatic hydrocarbon ring has 4 to 20 ring member carbon atoms and may have at least one substituent selected from the group consisting of alkyl group claim 1 , haloalkyl group claim 1 , cycloalkyl group claim 1 , alkoxy group claim 1 , amino group claim 1 , aralkyl group claim 1 , aryl group and halogen atom.4. The chromene compound according to claim 1 , wherein the ratio (A/A) of the color optical density (A: value of λ) of an absorption peak having a maximum absorption wavelength at 430 to 530 nm to the color optical density (A: value of λ) of an absorption peak having a maximum absorption wavelength at 550 to 650 nm is 0.80 to 2.00.5. A photochromic curable composition comprising the chromene compound of and a polymerizable monomer.6. A photochromic optical article having a polymer molded product comprising the chromene compound of dispersed therein as a constituent member.7. An optical article having an optical substrate all or part of at least one surface of which is covered with a polymer film comprising the chromene compound of dispersed therein as a constituent member.9. The chromene compound according to claim 2 , wherein in the above formula (2) claim 2 , Rand Rform an aliphatic hydrocarbon ring together with the 13-position carbon atom bonded thereto claim 2 , and the aliphatic hydrocarbon ring has 4 to 20 ring member carbon atoms and may have at least one substituent selected from the group consisting of alkyl group claim 2 , haloalkyl group claim 2 , cycloalkyl group claim 2 , alkoxy group claim 2 , amino group ...

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27-03-2014 дата публикации

NEW I-ARYLPIPERAZINIC LIGANDS OF 5-HT7 RECEPTOR AND USE THEREOF

Номер: US20140086834A1

The invention relates to a new class of compounds able to inhibit with high affinity and selectivity the 5-HT7 receptor. The invention also relates to the utilization of such compounds as medicaments useful in the treatment and prevention of 5-HT7 receptor relating disorders of the central nervous system. The invention also relates to the isotopically labeled compounds for use in vivo diagnosis or imaging of a 5-HT7 condition. 5. The compound according to selected from the group consisting of:1-(4-Methoxyphenoxy)-3-[4-(2-biphenyl)piperazin-1-yl]propan-2-ol,1-[4-[2-(4-Methoxyphenyl)phenyl]piperazin-1-yl]-3-phenoxy-propan-2-ol,1-(4-Methoxyphenoxy)-3-[4-[3-(2-pyridyl)-2-pyridyl]piperazin-1-yl]propan-2-ol,1-(4-Methoxyphenoxy)-3-[4-[3-(3-pyridyl)-2-pyridyl]piperazin-1-yl]propan-2-ol,1-(4-Methoxyphenoxy)-3-[4-[3-(4-pyridyl)-2-pyridyl]piperazin-1-yl]propan-2-ol,1-[4-(2-Fluoroethoxy)phenoxy]-3-[4-[3-(2-pyridyl)-2-pyridyl]piperazin-1-yl]propan-2-ol,1-[4-(2-Fluoroethoxy)phenoxy]-3-[4-[3-(3-pyridyl)-2-pyridyl]piperazin-1-yl]propan-2-ol,1-[4-(2-Fluoroethoxy)phenoxy]-3-[4-[3-(4-pyridyl)-2-pyridyl]piperazin-1-yl]propan-2-ol,1-[4-[2-(4-Methoxyphenyl)phenyl]piperazin-1-yl]-3-pyrimidin-2-yloxy-propan-2-ol,1-[4-[2-(4-Methoxyphenyl)phenyl]piperazin-1-yl]-3-pyrazin-2-yloxy-propan-2-ol,1-[4-[2-(4-Methoxyphenyl)phenyl]piperazin-1-yl]-3-pyrimidin-4-yloxy-propan-2-ol,1-[2-Fluoro-2-(3-methoxyphenyl)ethyl]4-[3-(2-pyridyl)-2-pyridyl)piperazine,1-[2-Fluoro-2-(3-methoxyphenyl)ethyl]4-[3-(3-pyridyl)-2-pyridyl)piperazine,1-[2-Fluoro-2-(3-methoxyphenyl)ethyl]4-[3-(4-pyridyl)-2-pyridyl)piperazine,1-[2-(3-Methoxyphenoxy)ethyl]4-[3-(2-pyridyl)-2-pyridyl]piperazine,1-[2-(3-Methoxyphenoxy)ethyl]4-[3-(3-pyridyl)-2-pyridyl]piperazine,1-[2-(3-Methoxyphenoxy)ethyl]4-[3-(4-pyridyl)-2-pyridyl]piperazine,1-[2-[4-(2-Fluoroethoxy)phenoxy]ethyl]4-[3-(2-pyridyl)-2-pyridyl]piperazine,1-[2-[4-(2-Fluoroethoxy)phenoxy]ethyl]4-[3-(3-pyridyl)-2-pyridyl]piperazine,1-[2-[4-(2-Fluoroethoxy)phenoxy]ethyl]4-[3-(4-pyridyl)-2 ...

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07-01-2016 дата публикации

N-HYDROXYLSULFONAMIDE DERIVATIVES AS NEW PHYSIOLOGICALLY USEFUL NITROXYL DONORS

Номер: US20160002156A1
Принадлежит:

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives. 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein each Rand Ris independently selected from the group consisting of Cl claim 1 , F claim 1 , I claim 1 , Br claim 1 , SOCH claim 1 , SONHOH claim 1 , CF claim 1 , CH claim 1 , NO claim 1 , phenyl claim 1 , CN claim 1 , OCH claim 1 , OCF claim 1 , t-Bu claim 1 , O-iPr claim 1 , 4-nitrophenyloxy (OPh4-NO) claim 1 , propane-2-thiyl (SCH(CH)) claim 1 , propane-2-sulfinyl (S(O)CH(CH)) claim 1 , morpholino claim 1 , N-methyl-piperazino claim 1 , dimethylamino claim 1 , piperidino claim 1 , cyclohexyloxy claim 1 , cyclopentylsulfanyl claim 1 , phenylsulfanyl and phenylsulfinyl.4. The compound of claim 1 , wherein the compound is of the formula (I).5. The compound of wherein the compound is of the formula (I) and at least one of Rand Ris other than H.6. The compound of claim 4 , wherein the compound is of the formula (I) and at least one of Rand Ris an electron withdrawing group.7. The compound of claim 4 , wherein the compound is of the formula (I) and R claim 4 , R claim 4 , R claim 4 , Rand Rare independently selected from the group consisting of H claim 4 , halo claim 4 , alkylsulfonyl claim 4 , N-hydroxylsulfonamidyl claim 4 , perhaloalkyl claim 4 , nitro claim 4 , aryl claim 4 , cyano claim 4 , alkoxy claim 4 , perhaloalkoxy claim 4 , alkyl claim 4 , substituted aryloxy claim 4 , alkylsulfanyl claim 4 , alkylsulfinyl claim 4 , heterocycloalkyl ...

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03-01-2019 дата публикации

Process and novel polymorphic form of vortioxetine and its pharmaceutically acceptable salts

Номер: US20190002421A1
Принадлежит: Apicore US LLC

Processes are disclosed for making vortioxetine and pharmaceutically acceptable salts thereof. A propylene glycol solvate of vortioxetine hydrobromide is disclosed. A novel crystalline form of vortioxetine hydrobromide propylene glycol solvate, designated form AC1, is disclosed along with a method for making same. Form AC1 may be characterized by an x-ray powder diffraction pattern with peaks at about 19.64, 22.85, 25.51, 29.57, 30.18±0.2 degrees 2-theta.

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14-01-2016 дата публикации

VORTIOXETINE MANUFACTURING PROCESS

Номер: US20160009670A1
Принадлежит:

A process for the manufacture of vortioxetine is provided in which a compound of formula I, formula I is reacted with optionally substituted piperazine and 2,4-dimethylthiophenol(ate) followed by de-complexation. 2. The process according to claim 1 , wherein Hal represents chloro.3. The process according to claim 1 , wherein R′ represents hydrogen.4. The process according to claim 1 , wherein R represents H.5. The process according to claim 1 , wherein R represents a protective group.6. The process according to claim 5 , wherein R represents a protective group selected from the group consisting of Boc claim 5 , Fmoc claim 5 , Bn and Cbz.7. The process according to claim 1 , wherein Xis selected from the group consisting of PF claim 1 , AlCl claim 1 , ClO claim 1 , BF claim 1 , [B[3 claim 1 ,5-(CF)CH]] claim 1 , B(CF) and Al(OC(CF)).8. The process according to claim 7 , wherein X is PF.9. The process according to claim 1 , wherein said solvent is selected from the group consisting of toluene claim 1 , THF (tetrahydrofuran) claim 1 , MTBE (methyl tertiary-butyl ether) claim 1 , water claim 1 , ethanol claim 1 , 2-propanol claim 1 , NMP (N-Methyl-2-pyrrolidone) claim 1 , DMF (dimethylformamide) claim 1 , MIBK (methylisobutyl ketone) claim 1 , TEA (triethyl amine) claim 1 , DIPEA (N claim 1 ,N-diisopropylethylamine) claim 1 , DCM (dichloromethane) claim 1 , ethylacetate claim 1 , isopropylacetate and combinations of these.109. The process according to any of - wherein R″ represents H.11. The process according to claim 1 , wherein said de-complexation step comprises photolysis.12. The process according to claim 1 , wherein 1 equivalent of a compound of formula I is mixed with a compound of formula II (1-5 equivalents) and a compound of formula III (1-5 equivalents) in a solvent together with a base as required (more than 0.5 equivalent) to obtain a compound of formula IV followed by de-complexation and removal of the protective group on the piperazine as required to ...

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27-01-2022 дата публикации

Crystalline ppar-delta agonist

Номер: US20220024888A1
Принадлежит: Reneo Pharma Ltd, Reneo Pharmaceuticals Inc

Described herein is crystalline sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate, uses of such crystalline material in the preparation of pharmaceutical compositions for the treatment of diseases or conditions that would benefit by administration with a PPARδ agonist compound.

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08-01-2015 дата публикации

ANTIMICROBIAL AGENTS

Номер: US20150011559A1
Принадлежит:

The invention provides methods of treating a bacterial infection in a mammal comprising administering to the mammal a compound of formula I: 2. The method of wherein ring A is phenyl claim 1 , which is substituted with one or more Rand which is optionally substituted with one or more R.3. The method of wherein ring A is thiazolyl claim 1 , which is substituted with one or more Rand which is optionally substituted with one or more R.4. The method of wherein Ris methyl claim 1 , phenyl claim 1 , tert-butyl claim 1 , bromo claim 1 , cyclohexyl claim 1 , thiazolyl claim 1 , biphenyl claim 1 , thiazol-2-ylaminocarbonyl claim 1 , or cyclopropyl.5. The method of wherein B is phenyl substituted with one or more Rand optionally substituted with one or more R.6. The method of wherein B is pyridyl substituted with one or more Rand optionally substituted with one or more R.7. The method of wherein B is thiazolyl substituted with one or more Rand optionally substituted with one or more R.9. The method of wherein each Ris selected from methoxy claim 1 , methyl claim 1 , N claim 1 ,N-dimethylaminomethyl claim 1 , bromo claim 1 , 4-tert-butylphenyl claim 1 , 4-trifluoromethoxy-2-methoxyphenyl claim 1 , nitro claim 1 , amino claim 1 , methylsulfonylamino claim 1 , methylcarbonylamino claim 1 , hydroxymethyl claim 1 , 2-(N claim 1 ,N-diethylamino)ethylaminocarbonyl claim 1 , methoxy claim 1 , —(OCHCH)—OCH claim 1 , 2 claim 1 ,2-dibromoethyl claim 1 , thiazol-2-ylaminocarbonyl claim 1 , and methoxycarbonyl.10. The method of wherein each Ris selected from methoxy claim 1 , N claim 1 ,N-dimethylaminomethyl claim 1 , bromo claim 1 , 4-tert-butylphenyl claim 1 , 4-trifluoromethoxy-2-methoxyphenyl claim 1 , nitro claim 1 , and methoxycarbonyl.13. The method of wherein each Ris independently selected from cyclopropyl claim 12 , tert-butyl claim 12 , bromo claim 12 , 4-tert-butylphenyl claim 12 , and phenyl that is substituted at the 4-position with halo.14. The method of wherein each Ris ...

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19-01-2017 дата публикации

USE OF ARYLALKANOLAMINES AS SIGMA-1 RECEPTOR ANTAGONISTS

Номер: US20170015640A1
Принадлежит:

The present invention relates to the use of arylalkanolamine compounds with sigma-1 receptor antagonist activity. In particular, the said arylalkanolamine compounds are useful in the treatment of conditions selected from the abuse of psychotropic substances such as cocaine or amphetamines, pain and cancer. 2. The aryl alkanolamine compounds according to claim 1 , wherein R1 and R2 claim 1 , equal to or different from each other claim 1 , are a linear or branched (C-C)alkyl group claim 1 , a benzyl group claim 1 , or R1 and R2 form claim 1 , together with the nitrogen atom to which they are bonded claim 1 , a 6-membered heterocyclic ring claim 1 , optionally comprising another heteroatom selected from N claim 1 , O and S.3. The aryl alkanolamine compounds according to claim 2 , wherein R1 and R2 claim 2 , equal to or different from each other claim 2 , are a methyl group claim 2 , an ethyl group claim 2 , a benzyl group claim 2 , or R1 and R2 form claim 2 , together with the nitrogen atom to which they are bonded claim 2 , a piperidine or morpholine ring.4. The aryl alkanolamine compounds according to claim 3 , wherein R1 and R2 form claim 3 , together with the nitrogen atom to which they are bonded claim 3 , a piperidine ring.5. The aryl alkanolamine compounds according to claim 1 , wherein R3 and R4 claim 1 , equal to or different from each other claim 1 , are hydrogen atom claim 1 , a phenyl group claim 1 , or R3 and R4 form claim 1 , together with the ring to which they are bonded claim 1 , an optionally substituted naphthalene ring.627.-. (canceled)28. The aryl alkanolamine compounds according to claim 5 , wherein said naphthalene ring formed by R3 and R4 is substituted with a hydroxy) group claim 5 , an alkoxy group having from 1 to 3 carbon atoms claim 5 , or a halogen atom.29. The aryl alkanolamine compounds according to claim 5 , wherein R3 is a hydrogen atom and R4 is a phenyl group.30. The aryl alkanolamine compounds according to claim 1 , wherein n is an ...

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15-01-2015 дата публикации

ANTIBACTERIAL AGENTS

Номер: US20150018331A1
Принадлежит: Achaogen, Inc.

Antibacterial compounds of formula (I) are provided: 137-. (canceled)39. A compound of wherein A is —C(R claim 38 ,R)N(R claim 38 ,R).40. A compound of wherein A is —C(CH)NH.41. A compound of wherein A is —C(R claim 38 ,R)OR.42. A compound of wherein A is selected from the group consisting of:{'sub': 3', '10, '(1) substituted or unsubstituted C-C-cycloalkyl,'}(2) substituted or unsubstituted heterocyclyl, and(3) substituted or unsubstituted heteroaryl.44. (canceled)45. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,{'sup': 3G', '3G, '(3) —CR═CR—C≡C—, and'}{'sup': 3G', '3G, '(4) —C≡C—CR═CR—.'}46. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,(3) —CH═CH—C≡C—, and(4) —C≡C—CH═CH—.47. A compound of wherein G is —C≡C—.48. A compound of wherein G is —C≡C—C≡C—.49. A compound of wherein G is —CH═CH—C≡C—.50. (canceled)51. A compound of wherein G is —C≡C—CH═CH—.5257-. (canceled)58. A compound of wherein Ris H.59. A compound of wherein Y is substituted or unsubstituted aryl.60. A compound of wherein Y is substituted or unsubstituted phenyl.61. A compound of wherein Y is unsubstituted phenyl.62. (canceled)63. A compound of wherein D is substituted or unsubstituted heteroaryl.6467-. (canceled)68. A compound of wherein D is absent.6972-. (canceled)73. A compound of wherein L is absent.74. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier or diluent.75. A method for treating a subject with a gram-negative bacterial infection comprising administering to the subject in need thereof an antibacterially effective amount of a compound of or a pharmaceutical composition of .76. (canceled) This application is a continuation of U.S. patent application Ser. No. 12/635,551, filed Dec. 10, 2009, now pending, which is a continuation of International PCT Application No. PCT/US2008/066766, filed Jun. 12, 2008, which claims the benefit under 35 U.S.C. §119(e) of U.S. ...

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21-01-2021 дата публикации

BICYCLIC COMPOUNDS AS INHIBITORS OF PD1/PD-L1 INTERACTION/ACTIVATION

Номер: US20210015810A1
Принадлежит:

The compounds of Formula I is described herein along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof. The compounds described herein, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof are bicyclic compounds that are inhibitors of PD-1/PD-L1 interaction/activation. 7. The compounds of Formula I or its polymorphs claim 1 , stereoisomers claim 1 , tautomers claim 1 , prodrugs claim 1 , solvates claim 1 , and pharmaceutically acceptable salts thereof claim 1 , as claimed in claim 1 , is selected from a group consisting of:(S)-1-((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl) piperidine-2-carboxylic acid (1),N-(2-(((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (2),(S)-1-((7-((3-(1-(3-(3,3-difluoropyrrolidin-1-yl)propyl)-1H-indol-4-yl)-2-methylbenzyl)oxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (3),(S)-1-((6-methyl-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (4),(S)-1-((6-chloro-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (5),Methyl 7-(((2-acetamidoethyl)amino)methyl)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-indene-5-carboxylate (6),(S)-1-((7-((3′-(3-(3,3-difluoropyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (7),(S)-1-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (8),(S)-1-((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (9)N-(2-(((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4- ...

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01-02-2018 дата публикации

PROCESS FOR THE PREPARATION OF VORTIOXETINE

Номер: US20180030008A1
Принадлежит:

Disclosed herein a process for the isolation of intermediate of Vortioxetine in a solid state form and an improved, commercially viable and industrially advantageous process for the preparation of vortioxetine or a pharmaceutically acceptable salt thereof, in high yield and purity. 2. The process according to wherein the reaction of step (a) and step (b) of method A claim 1 , B claim 1 , C claim 1 , D claim 1 , E and F can be carried out in the presence of a base claim 1 , a palladium catalyst claim 1 , a ligand and a solvent.3. (canceled)4. The process according to claim 2 , wherein the solvent is an organic solvent selected from the group consisting of methylene chloride claim 2 , ethylene dichloride claim 2 , chloroform claim 2 , carbon tetrachloride claim 2 , n-pentane claim 2 , n-hexane claim 2 , n-heptane claim 2 , cyclohexane claim 2 , toluene claim 2 , xylene claim 2 , acetone claim 2 , methyl ethyl ketone claim 2 , methyl isobutyl ketone claim 2 , methyl tert-butyl ketone claim 2 , acetonitrile claim 2 , ethyl acetate claim 2 , methyl acetate claim 2 , isopropyl acetate claim 2 , tert-butyl methyl acetate claim 2 , ethyl formate claim 2 , tetrahydrofuran claim 2 , dioxane claim 2 , diethyl ether claim 2 , diisopropyl ether claim 2 , monoglyme claim 2 , diglyme claim 2 , N claim 2 ,N-dimethylformamide claim 2 , and N claim 2 ,N-dimethylacetamide claim 2 , dimethylsulfoxide; or mixtures of at least two thereof.5. The process according to claim 2 , wherein the palladium catalyst is selected from the group consisting of Tris (dibenzylideneacetone) dipalladium (Pd(dba)) claim 2 , Bis (dibenzylideneacetone) palladium (Pd(dba)) and Palladium(II) acetate (Pd(OAc)).6. The process according to claim 2 , wherein the ligand is selected from the group consisting of racemic 2 claim 2 ,2′-bis-diphenylphosphanyl-[1 claim 2 ,1′]binaphtalenyl (rac-BINAP) claim 2 , 1 claim 2 ,1′-bis (diphenylphosphino) ferrocene (DPPF) claim 2 , bis-(2-diphenylphosphinophenyl)ether (DPEphos) ...

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30-01-2020 дата публикации

PLEUROMUTILIN DERIVATIVES FOR THE TREATMENT OF DISEASES MEDIATED BY MICROBES

Номер: US20200030335A1
Принадлежит:

A compound of formula (I) wherein n is 0 to 4; m is 0 or 1 with the proviso that the sulphur atom and Rare in vicinal position (if m=0 then Ris in position 2′, and if m=1 then Ris on position 1′); R is ethyl or vinyl; Ris hydrogen or (C1-6)alkyl; Ris hydrogen or —(C)cycloalkyl, or —unsubstituted (C)alkyl, or —(C)alkyl substituted by one or more of —hydroxy; preferably one or two, —methoxy, —halogen, —(C)cycloalkyl, or Rand Rtogether with the nitrogen atom to which they are attached form a 5 to 7 membered heterocyclic ring containing at least 1 nitrogen atom or 1 nitrogen and 1 additional heteroatome e.g. selected from N or O, or Ris hydroxy and Ris formyl; Ris OH, OR, a halogen atom, or —with the proviso that Ris bound to 2′ Rrepresents —O—(CH)P—O— with p is 2 or 3; Ris unsubstituted (C)alkyl or (C)cycloalkyl. 8. The compound according to any of to in the form of a salt and/or solvate.9. A compound according to any of to for use as a pharmaceutical drug substance.10. A method of treatment of diseases mediated by microbes which comprises administering to a subject in need of such treatment an effective amount of a compound of any one of to .11. A pharmaceutical drug composition comprising a compound of anyone of to , in association with at least one pharmaceutical excipient.12. A pharmaceutical drug composition according to claim 11 , further comprising another pharmaceutically active agent. The present invention relates to organic compounds, namely pleuromutilins.Pleuromutilin, a compound of formula Ais a naturally occurring antibiotic, e.g. produced by the basidomycetes and , see e.g. The Merck Index, 13th edition, item 7617. A number of further pleuromutilins having the principle ring structure of pleuromutilin and being substituted at the hydroxy group have been developed, e.g. as antimicrobials.From WO 02/04414 A1 pleuromutilin derivatives, e.g. 14-O-[(Aminocyclohexan-2-yl (and -3-yl)-sulfanyl)-acetyl]-mutilins; from WO 07/014409 A1e.g. 14-O-[((Mono- or ...

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11-02-2016 дата публикации

METAL NANO-CATALYSTS IN GLYCEROL AND APPLICATIONS IN ORGANIC SYNTHESIS

Номер: US20160038926A1
Принадлежит:

A catalytic system which is a suspension in glycerol of metal nanoparticles in at least one transition metal. The suspension also includes at least one compound stabilizing the metal nanoparticles, soluble in glycerol. The suspensions are obtained directly in glycerol. These are stable systems that can catalyse a reaction from an organic substrate, with high yields and activity, and excellent selectivity. Additionally, the use of the catalytic system for performing organic transformations such as hydrogenation or coupling reactions (formation of C—C, C—N, C—O, C—S . . . bonds), and for synthesizing polyfunctionnal molecules, in a single reactor, by multi-step, sequential or cascade reactions. 119-. (canceled)20. A catalytic system , consisting of a suspension in glycerol of metal nanoparticles comprising at least one transition metal , said suspension also comprising at least one glycerol-soluble stabilizing compound which stabilizes said metal nanoparticles.21. The system as claimed in claim 20 , wherein said nanoparticles comprise a metal having a zero oxidation state chosen from the transition metals from Groups VI to XI.22. The system as claimed in claim 20 , wherein said nanoparticles comprise an oxide of a transition metal having a given oxidation state claim 20 , said metal being chosen from the metals of the first transition series.23. The system as claimed in claim 20 , wherein said nanoparticles comprise a metal chosen from copper claim 20 , palladium claim 20 , rhodium and ruthenium.24. The system as claimed in claim 20 , wherein said stabilizing compound is a ligand of said transition metal chosen from glycerol-soluble phosphines.25. The system as claimed in claim 24 , wherein said stabilizing compound is the sodium salt of tris(3-sulfophenyl)phosphine claim 24 , with a molar ratio of said ligand to said metal being of between 0.1 and 2.0.26. The system as claimed claim 20 , wherein said transition metal is at a concentration in the glycerol of between ...

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09-02-2017 дата публикации

Sulfonamide Derivatives And Pharmaceutical Applications Thereof

Номер: US20170037017A1
Принадлежит: SUNSHINE LAKE PHARMA CO., LTD.

Provided herein are sulfonamide derivatives or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and their uses for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and use of such compounds or pharmaceutical compositions thereof for managing or treating 5-HTreceptor-mediated diseases, especially in the manufacture of a medicament for managing or treating Alzheimer's disease. 2. The compound according to claim 1 , wherein Ris 3- to 8-membered heterocyclyl claim 1 , and wherein optionally the heterocyclyl is independently substituted with 1 claim 1 , 2 claim 1 , 3 or 4 substitutents independently selected from H claim 1 , D claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , oxo (═O) claim 1 , —C(═O)R claim 1 , —C(═O)OR claim 1 , —C(═O)NRR claim 1 , Calkyl claim 1 , Ccycloalkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Chaloalkoxy claim 1 , (Caryl)-(Calkyl)- or (5- to 12-membered heteroaryl)-(Calkyl)-; and{'sup': 9', '9a', '9b', '9c, 'sub': '1-4', 'each of R, R, Rand Ris independently H, D, —OH or Calkyl.'}4. The compound according to claim 1 , wherein each Rand Ris independently H claim 1 , D claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccycloalkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Chaloalkoxy claim 1 , 3- to 8-membered heterocyclyl claim 1 , 5- to 9-membered heteroaryl or Caryl.5. The compound according to claim 1 , wherein each Ris independently H claim 1 , D claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , Calkyl claim 1 , Calkenyl claim 1 , C-alkynyl claim 1 , Ccycloalkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Chaloalkoxy or Caryl; or two adjacent R claim 1 , together with the carbon ...

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07-02-2019 дата публикации

Synthesis of 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]piperazine

Номер: US20190040027A1
Принадлежит:

The invention relates to a method for synthesis of 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]piperazine in the presence of a strong base. 1. A method for preparing 1-[2-(2 ,4-Dimethyl-phenylsulfanyl)-phenyl]piperazine , said method comprising the steps ofa. providing piperazine;b. providing an electrophile selected from the group consisting of 1, 2-di-fluorobenzene, 2-chloro-fluorobenzene, 1, 2-di-chlorobenzene, 2-(2,4-di-methyl-thiophenol-yl)-chlorobenzene, and 2-(2,4-di-methyl-thiophenol-yl)-fluorobenzene;c. providing a base having a pKa above 29 in DMSO and/or a pKa above 25 in THF;d. providing an organic solvent that only contain protons with a pKa above 32 in DMSO;e. reacting said piperazine with said electrophile in said organic solvent in the presence of the base and in the absence of a transition metal catalyst, thereby obtainingi. 1-[2-fluoro-phenyl]piperazine or 1-[2-chloro-phenyl]piperazine; orii. 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine,f. if obtaining 1-[2-fluoro-phenyl]piperazine or 1-[2-chloro-phenyl]piperazine in step e. reacting said 1-[2-fluoro-phenyl]piperazine or 1-[2-chloro-phenyl]piperazine with 1-sulfanyl-2,4-dimethyl-benzene, thereby obtaining 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]piperazine;g. optionally purifying the 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine;wherein steps a., b., c. and d. is performed in any order.2. The method according to claim 1 , wherein 2-(2 claim 1 ,4-di-methyl-thiophenol-yl)-chlorobenzene or 2-(2 claim 1 ,4-di-methyl-thiophenol-yl)-fluorobenzene has been obtained by reactingi. 1, 2-di-fluorobenzene, 2-chloro-fluorobenzene, or 1, 2-di-chlorobenzene withii. 2,4-dimethyl-phenylsulfanyl.3. The method according to claim 1 , wherein step e. comprises the sub-steps of i) reacting said nucleophile with said base and ii) reacting the product of step i) with said electrophile claim 1 , and wherein sub-steps i) and ii) are performed in the indicated order.4. The method according to claim 1 , wherein ...

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07-02-2019 дата публикации

ARYLATION OF ALIPHATIC AMINES

Номер: US20190040028A1
Принадлежит:

The invention relates to a method for arylation of amines, such as aliphatic amines by reaction of aryl-halogens, e.g. chloro- or fluorobenzene derivatives without strongly electron withdrawing substituents in the presence of a strong base. 1. A method for preparing an arylated amine , said method comprising the steps of{'sub': '2', 'a. Providing a nucleophile, wherein said nucleophile comprises an —NH— or an —NHgroup directly linked to only non-aromatic carbon atoms or a salt of said nucleophile;'}b. Providing an electrophile, wherein said electrophile is aryl substituted with at least two substituents, wherein the first substituent is halogen and the second substituent and any further optional substituent(s) are selected from the group consisting of halogen, aryl, substituted aryl, alkenyl, substituted alkenyl, heteroalkenyl, alkyl, substituted alkyl, heteroalkyl, alkoxy, substituted alkoxy, amino, thioalkyl, substituted thioalkyl, thioaryl, substituted thioaryl, heteroaryl, and phosphinyl, with the proviso that said aryl is substituted with at the most 4 halogens;c. Providing a base, wherein the corresponding acid has a pKa above 29 in DMSO and/or a pKa above 25 in THF;d. Providing an organic solvent that only contain protons with a pKa above 32 in DMSO.e. Reacting said nucleophile with said electrophile in said organic solvent in the presence of the base, thereby obtaining an arylated amine consisting of said aryl, wherein the first substituent is substituted by said amine;f. Optionally purifying the arylated amine,wherein steps a., b., c. and d. may be performed in any order.2. The method according to claim 1 , wherein step e. is performed in the absence of a transition metal catalyst.3. The method according to claim 1 , wherein step b. consists of providing an electrophile claim 1 , wherein said electrophile is aryl substituted with at least two substituents claim 1 , wherein the first substituent is halogen and the second substituent and any further optional ...

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13-02-2020 дата публикации

USE OF A PPAR-DELTA AGONIST FOR REDUCING LOSS OF MUSCLE STRENGTH, MUSCLE MASS, OR TYPE I MUSCLE FIBERS IN AN IMMOBILIZED LIMB

Номер: US20200046717A1
Принадлежит:

The present invention provides methods for reducing loss of muscle strength, muscle mass, or Type I muscle fibers in an immobilized limb by administering (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof. 1. A method of treatment comprising administering to a human subject (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof ,wherein the human subject has an immobilized limb, andwherein the amount of (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof administered is sufficient to reduce the rate of loss of muscle strength in the muscle tissue of the immobilized limb of the subject relative to a control,wherein muscle strength is measured by a muscle strength test.2. The method of claim 1 , wherein the rate of loss of muscle strength comprises a comparison of muscle strength in the subject's immobilized limb to a baseline measurement of muscle strength in the same limb prior to a period of immobilization.3. The method of claim 1 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength faster than the control following a period of immobilization.4. The method of claim 1 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength following a period of disuse in less than 90% of the time to return to baseline for a control.5. The method of claim 1 , wherein the loss of muscle strength in the subject's immobilized limb is less than the loss of muscle strength relative to the control during a period of immobilization.6. The method of claim 1 , wherein (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl) ...

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25-02-2016 дата публикации

Novel Intermediate Used for Preparing Tapentadol or Analogues Thereof

Номер: US20160052866A1
Принадлежит:

The invention discloses a novel intermediate for preparing tapentadol and analogues thereof, wherein the structural formula is shown as formula I or II, and the groups are defined as the specification. The invention further discloses a method for preparing the novel intermediate and use of the intermediate for preparing tapentadol and analogues thereof. The invention can remarkably improve the product yield and quality of tapentadol, reduce the production cost, and simplify the production procedure. The preparation process is environment friendly, thus more suitable for the requirements of industrial production. 2. The compound according to claim 1 , wherein Ris selected from Cl claim 1 , methyl claim 1 , OH hydroxy claim 1 , NHamino or methoxy.3. The compound according to claim 1 , characterized in that Y is selected from OR claim 1 , wherein Ris selected from methyl claim 1 , ethyl claim 1 , n-propyl or isopropyl.4. The compound according to claim 1 , characterized in that Y is selected from NRR claim 1 , wherein R claim 1 , Rand N form substituted or unsubstituted saturated nitrogen-containing heteorcyclyl containing oxygen or not jointly.5. The compound according to claim 4 , wherein R claim 4 , Rand N form tetrahydropyrrole ring claim 4 , piperidine ring claim 4 , 4-methylpiperidine ring claim 4 , morpholine ring claim 4 , methylpiperazine ring or 4-hydroxypiperidine jointly.6. The compound according to claim 1 , selected from the following compounds:valeryl 2-methyl-3-(3-methoxyphenyl)chloride;methyl 2-methyl-3-(3-methoxyphenyl)sulfovalerate;methyl 2-methyl-3-(3-hydroxyphenyl)sulfovalerate;2-methyl-3-(3-hydroxyphenyl)sulfovaleramide;N,N-dimethyl-2-methyl-3-(3-methoxyphenyl)sulfovaleramide;N,N-dimethyl-2-methyl-3-(3-hydroxyphenyl)sulfovaleramide;N,N-diethyl-2-methyl-3-(3-methoxyphenyl)valeramide;3-(3-methoxyphenyl)-2-methyl-1-(piperidin-1-yl)pentan-1-one;3-(3-methoxyphenyl)-2-methyl-1-(4-methylpiperidin-1-yl)pentan-1-one;3-(3-methoxyphenyl)-2-methyl-1-( ...

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10-03-2022 дата публикации

USE OF A PPAR-DELTA AGONIST FOR REDUCING LOSS OF MUSCLE STRENGTH, MUSCLE MASS, OR TYPE I MUSCLE FIBERS IN AN IMMOBILIZED LIMB

Номер: US20220072005A1
Принадлежит:

The present invention provides methods for reducing loss of muscle strength, muscle mass, or Type I muscle fibers in an immobilized limb by administering (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof. 1. A method of treating muscle atrophy in a subject comprising administering to the subject in need thereof a small molecule PPARδ agonist , wherein the PPARδ agonist: has a molecular weight of less than 1000 g/mol; an EC50 value of less than 500 nM as determined by a PPARδ transient transactivation assay; and at least a 10-fold potency for activation of PPARδ relative to either or both of PPARα and PPARγ.2. The method of claim 1 , wherein the small molecule PPARδ agonist: increases muscle mass in the subject; modulates muscle growth claim 1 , enhances muscle formation claim 1 , increases muscle strength claim 1 , maintains muscle strength or reduces loss of muscle strength in the subject; or reducing the rate of decrease in mitochondrial biogenesis in a muscle tissue; or combination thereof.3. A method of modulating muscle in a subject with muscle atrophy comprising administering to the subject in need thereof a selective PPARδ agonist claim 1 , wherein the muscle modulation is selected from: increasing muscle mass in the subject; modulating muscle growth claim 1 , enhancing muscle formation claim 1 , increasing muscle strength claim 1 , maintaining muscle strength or reducing loss of muscle strength in the subject; or reducing the rate of decrease in mitochondrial biogenesis in a muscle tissue; or combination thereof; and wherein the selective PPARδ agonist is characterized by at least a 10-fold potency for activation of PPARδ relative to either or both of PPARα and PPARγ.4. The method of claim 3 , wherein the small molecule PPARδ agonist reduces the rate of loss of Type I muscle fibers.5. The method of claim 1 , wherein the treatment comprises activating PPARδ ...

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03-03-2016 дата публикации

New Process For The Synthesis Of 1-(2-((2,4-Dimethylphenyl)Thio)Phenyl)Piperazine

Номер: US20160060215A1
Автор: Zupancic Borut
Принадлежит: Lek Pharmaceuticals D.D.

The present invention provides new intermediate compounds or formulae (III) and (IVa), and salts thereof, and their use in a new synthetic process for the production of 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine (vortioxetine) an experimental drug under development for the treatment of depression and anxiety. 1. (canceled)4. A process according to claim 3 , wherein the reducing agent is thiourea dioxide claim 3 , sodium dithionite claim 3 , iron or zinc.5. (canceled)8. A process according to claim 7 , wherein:LG is selected from F, Cl, Br, OTs and OTf;{'sup': '1', 'Rrepresents hydrogen; and'}{'sub': 2', '3', '2', '3, 'the base is NaCOor KCO.'}10. A process according to wherein:LG is selected from F, Cl, Br, OTs and OTf;{'sup': '1', 'Rrepresents hydrogen;'}{'sub': 2', '3', '2', '3, 'the base is NaCOor KCO; and'}the reducing agent used in step (ii) is thiourea dioxide or sodium dithionite.11. A process according to wherein the reaction steps (i) and (ii) are carried out in the same reaction vessel.13. A process according to wherein the piperazine ring forming agent is selected from bis(2-chloroethyl)amine or a salt thereof claim 12 , diethanolamine and morpholine.14. A process according to which comprises the additional step of converting the compound of formula (V) claim 12 , or salt thereof claim 12 , to its hydrobromide salt. This invention relates to a new and advantageous process for the synthesis of 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine (vortioxetine) an experimental drug under development for the treatment of depression and anxiety.Vortioxetine is disclosed as Example 1e in WO 2003/029232 A1 and is described as being prepared analogously to Example 1. The process used to prepare Example 1 involves the preparation of 1-(2-((2-(trifluoromethyl)phenyl)thio)phenyl)piperazine on a solid polystyrene support, followed by decomplexation using visible light irradiation, and purification by preparative LC-MS and ion-exchange chromatography. The overall ...

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01-03-2018 дата публикации

AMINATION AND HYDROXYLATION OF ARYLMETAL COMPOUNDS

Номер: US20180057444A1
Принадлежит: William Marsh Rice University

In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions. 1. A method of preparing an aminoaromatic group or a hydroxyaromatic group comprising:(A) admixing a metal aromatic compound with an oxaziridine compound to form a first reaction mixture under conditions sufficient to cause a reaction to obtain an anionic intermediate;(B) admixing a weak acid with the anionic intermediate and the first reaction mixture to obtain a second reaction mixture under conditions sufficient to obtain an aminoaromatic group or a hydroxyaromatic group.2. The method of claim 1 , wherein the metal of the metal aromatic compound is attached to one of the carbon atoms of the aromatic ring.3. The method of claim 1 , wherein the metal of the metal aromatic compound is a magnesium halide or lithium.48-. (canceled)9. The method of claim 1 , wherein the metal aromatic compound is substituted.10. (canceled)11. The method of claim 9 , wherein the metal aromatic compound is substituted with a substituent wherein the substituent is amino claim 9 , aminosulfonyl claim 9 , carboxy claim 9 , cyano claim 9 , halo claim 9 , hydroxy claim 9 , hydroxyamino claim 9 , hydroxysulfonyl claim 9 , mercapto claim 9 , nitro claim 9 , oxo claim 9 , or thio; or acyl claim 9 , alkoxy claim 9 , cycloalkoxy claim 9 , alkenyloxy claim 9 , aryloxy claim 9 , aralkoxy claim 9 , acyloxy claim 9 , cycloalkylalkoxy claim 9 , heterocycloalkylalkoxy claim 9 , heterocycloalkoxy claim 9 , alkylthio claim 9 , cycloalkylthio claim 9 , amido claim 9 , alkylamino claim 9 , dialkylamino claim 9 , alkylsulfonyl claim 9 , arylsulfonyl claim 9 , or a substituted version of these groups ...

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12-03-2015 дата публикации

USE OF A PPAR-DELTA AGONIST FOR TREATING MUSCLE ATROPHY

Номер: US20150072985A1
Принадлежит:

The present invention provides methods for treating muscle atrophy by administering a PPARδ agonist. 1. A method for reducing disuse-associated muscle atrophy in a subject in need thereof comprising administering to the subject an effective amount of a PPARδ agonist.2. The method of claim 1 , wherein the disuse-associated muscle atrophy is caused by limb immobilization in the subject.3. The method of claim 1 , wherein the disuse-associated muscle atrophy is caused by use of a mechanical ventilator by the subject.4. The method of claim 1 , wherein reducing disuse-associated muscle atrophy comprises reducing the rate of loss of muscle strength in a muscle tissue of the subject relative to a control claim 1 , wherein the rate of loss of muscle strength comprises a comparison of one or more measurements of muscle strength in the subject to a baseline measurement of muscle strength in the same subject prior to a period of disuse claim 1 , wherein muscle strength is measured by a muscle strength test.5. The method of claim 4 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength faster than the control following a period of disuse.6. The method of claim 4 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength following a period of disuse in less than 90% of the time to return to baseline for a control.7. The method of claim 4 , wherein the loss of muscle strength in the subject is less than the loss of muscle strength relative to the control during a period of disuse.8. The method of claim 4 , wherein the loss of muscle strength in the subject comprises less than a 10% loss of muscle strength relative to the subject's baseline measurement of muscle strength prior to a period of disuse.9. The method of claim 1 , wherein reducing disuse-associated muscle atrophy comprises reducing the rate of ...

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15-03-2018 дата публикации

Methods for Making Serotonin Reuptake Inhibitors

Номер: US20180072690A1
Принадлежит: CIPLA LIMITED

The present invention relates to a process for preparing serotonin reuptake inhibitors of formula (I) and pharmaceutically acceptable salts thereof, (Formula (I)) wherein, R, R, R, l, m, n and Z are as defined in the specification. 2. A process according to claim 1 , wherein the base is an inorganic base selected from the group consisting of alkali or alkaline earth metal carbonates claim 1 , alkali or alkaline earth metal hydroxides claim 1 , alkoxides and metal phosphates.3. A process according to claim 2 , wherein the inorganic base is selected from the group consisting of cesium carbonate claim 2 , sodium carbonate claim 2 , potassium carbonate claim 2 , magnesium carbonate claim 2 , calcium carbonate claim 2 , barium carbonate claim 2 , sodium hydroxide claim 2 , potassium hydroxide claim 2 , lithium hydroxide claim 2 , magnesium hydroxide claim 2 , calcium hydroxide claim 2 , barium hydroxide claim 2 , sodium t-butoxide claim 2 , potassium t-butoxide claim 2 , monopotassium phosphate claim 2 , dipotassium phosphate and tripotassium phosphate claim 2 , or any combination thereof.4. A process according to claim 1 , wherein the base is an organic base selected from the group consisting of triethyl amine claim 1 , di-isopropyl amine claim 1 , pyridine claim 1 , picoline claim 1 , diethyl amine claim 1 , piperidine claim 1 , N claim 1 ,N-diisopropylethylamine and 1 claim 1 ,8-diazabicyclo [5.4.0]undec-7-ene (DBU) claim 1 , or any combination thereof.5. A process according to claim 1 , wherein the copper catalyst comprises a Cu(I) or Cu(II) salt.6. A process according to claim 5 , wherein the copper catalyst comprises copper iodide (CuI).7. A process according to claim 1 , wherein the copper catalyst is present in an amount ranging from about 0.5 mole % to about 10 mole %.8. A process according to any claim 1 , wherein the coupling reaction is performed in the presence of a solvent.9. A process according to claim 8 , wherein the solvent is a polar aprotic solvent ...

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05-03-2020 дата публикации

SPHINGOSINE KINASE TYPE 1 INHIBITORS AND USES THEREOF

Номер: US20200069611A1
Принадлежит:

Provided are inhibitors of sphingosine kinase Type I that are useful in a number of applications, indications and diseases, as well as for monitoring pharmacokinetics and patient management. These compounds are applicable to treating tumors of the central nervous system, such as glioblastoma multiforme (GBM). 5. The method of claim 4 , wherein R is a straight carbon chain claim 4 , a branched carbon chain claim 4 , a straight carbon chain comprising one or more heteroatoms claim 4 , a branched carbon chain comprising one or more heteroatoms claim 4 , a cyclic ring claim 4 , a heterocyclic ring claim 4 , an aromatic ring claim 4 , a hetero-aromatic ring claim 4 , or any combination of the foregoing.6. The method of claim 5 , wherein R is a straight carbon chain claim 5 , a branched carbon chain claim 5 , a straight carbon chain comprising one or more heteroatoms claim 5 , a branched carbon chain comprising one or more heteroatoms claim 5 , a cyclic ring claim 5 , a heterocyclic ring claim 5 , an aromatic ring claim 5 , or a hetero-aromatic ring.7. The method of claim 6 , wherein R is a straight carbon chain claim 6 , a branched carbon chain claim 6 , a straight carbon chain comprising one or more heteroatoms claim 6 , or a branched carbon chain comprising one or more heteroatoms.8. The method of claim 7 , wherein R is a straight carbon chain or a branched carbon chain.9. The method of claim 8 , wherein R is a straight carbon chain. This application is a continuation of U.S. application Ser. No. 16/199,337 filed Nov. 26, 2018, which is a continuation of U.S. application Ser. No. 15/954,131 filed Apr. 16, 2018, (now U.S. Pat. No. 10,166,204), which is a continuation of U.S. application Ser. No. 15/181,826 filed Jun. 14, 2016 (now U.S. Pat. No. 9,974,758), which is a continuation of U.S. application Ser. No. 13/649,221 filed Oct. 11, 2012 (now U.S. Pat. No. 9,388,121), which is a divisional of U.S. application Ser. No. 12/584,131 filed Aug. 31, 2009 (now U.S. Pat. No. 8 ...

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19-03-2015 дата публикации

Diamine derivatives as inhibitors of leukotriene a4 hydrolase

Номер: US20150080382A1
Принадлежит: Celtaxsys Inc

This invention is directed to compounds of formula (I): where r, q, R, R 2 , R 3 , R 4 , R 5a , R 5b , R 5c , R 6a , R 6b , R 6c , R 7 , R 8 , and R 9 are described herein, as single stereoisomers or as mixtures of stereoisomers, or pharmaceutically acceptable salts, solvates, clathrates, polymorphs, ammonium ions, N-oxides or prodrugs thereof; which are leukotriene A 4 hydrolase inhibitors and therefore useful in treating inflammatory disorders. Pharmaceutical compositions comprising the compounds of the invention and methods of preparing the compounds of the invention are also disclosed.

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05-06-2014 дата публикации

PROCESSES FOR THE PREPARATION OF ENAMINES

Номер: US20140155628A1
Принадлежит: DOW AGROSCIENCES LLC

The invention disclosed in this document is related to the field of processes for the preparation of enamines 1 (1) wherein said first mixture comprises pyrrolidine, and', '(2) wherein said second mixture comprises 3-methylsulfanyl-butyraldehyde and toluene, and', '(3) wherein said first mixture is contacted with said second mixture below the surface of said second mixture;', {'sub': '2', '(B) reacting in said reaction zone said pyrrolidine and said 3-methylsulfanyl-butyraldehyde to produce 1-(3-methylsulfanyl-but-1-enyl)-pyrrolidine and HO, wherein said reacting is conducted under azeotropic distillation conditions comprising'}, '(1) a pressure from about 5000 Pa to about 15000 Pa, and', '(2) a temperature from about 25° C. to about 65° C.; and, '(A) contacting a first mixture with a second mixture in a reaction zone'}{'sub': '2', 'claim-text': wherein the ratio of', '(the amount of first mixture added): (the vapor phase removed) is from about', '(1 part first mixture added): (3 parts vapor phase removed) to about', '(1 part first mixture added): (10 parts vapor phase removed);, '(C) removing a vapor phase comprising toluene and HO and essentially no 3-methylsulfanyl-butyraldehyde,'}{'sub': '2', 'wherein said process no desiccants are used to remove HO in said process; and'}wherein said process the molar ratio of amine to carbonyl is greater than 1 but less than about 1.1.. A process comprising: This Application is a continuation of U.S. non-provisional application Ser. No. 13/303,206, filed 23 Nov. 2011, which claims priority from and benefit of U.S. provisional application 61/419,277, filed on Dec. 3, 2010. The entire contents of these applications are hereby incorporated by reference into this Application.The invention disclosed in this document is related to the field of processes for the preparation of enamines.Enamines are very useful molecules. They have been used in a wide variety of reactions such as, for example, electrophilic substitution and addition, ...

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05-06-2014 дата публикации

PROCESSES FOR THE PREPARATION OF ENAMINES

Номер: US20140155629A1
Принадлежит: DOW AGROSCIENCES LLC

The invention disclosed in this document is related to the field of processes for the preparation of enamines 1{'sub': '2', 'claim-text': (1) a pressure from about 5000 Pascals (Pa) to about 15,000 Pa, and', '(2) a temperature from about 25° C. to about 65° C.; and, '(A) reacting, in a reaction zone that comprises solvents, pyrrolidine and 3-methylsulfanyl-butyraldehyde to produce 1-(3-methylsulfanyl-but-1-enyl)-pyrrolidine and HO, wherein said reacting, in said reaction zone, is conducted under azeotropic distillation conditions comprising'}{'sub': 2', '2', '2, 'wherein said solvents are initially toluene and acetonitrile, and then HO, where said HO is produced from the condensation of said pyrrolidine and said 3-methylsulfanyl-butyraldehyde to produce said 1-(3-methylsulfanyl-but-1-enyl)-pyrrolidine, thereby forming a ternary azeotrope of toluene, acetonitrile, and HO; and'}{'sub': '2', '(B) removing a vapor phase from said reaction zone wherein said vapor phase comprises HO;'}{'sub': '2', 'wherein said process no desiccants are used to remove HO;'}wherein said process said molar ratio of pyrrolidine to 3-methylsulfanyl-butyraldehyde is greater than 1 but less than about 1.1.. A process to produce 1-(3-methylsulfanyl-but-1-enyl)-pyrrolidine said process comprising: This Application is a continuation of U.S. non-provisional application Ser. No. 13/303,195, filed on 23 Nov. 2011, which claims priority from, and benefit of U.S. provisional application 61/419,300, filed on Dec. 3, 2010. The entire content of these applications are hereby incorporated by reference into this Application.The invention disclosed in this document is related to the field of processes for the preparation of enamines.Enamines are very useful molecules. They have been used in a wide variety of reactions such as, for example, electrophilic substitution and addition, oxidation and reduction, and cycloaddition (J. Kang, Y. R. Cho, and J. H. Lee, 13, No. 2 , 1992).An early method for preparing ...

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05-06-2014 дата публикации

Processes for the Preparation of Enamines

Номер: US20140155630A1
Принадлежит: DOW AGROSCIENCES LLC

The invention disclosed in this document is related to the field of processes for the preparation of enamines 1 (1) wherein said first mixture comprises a carbonyl wherein said carbonyl is 3-methylsulfanyl-butyraldehyde, and', '(2) wherein said second mixture comprises toluene and an amine wherein said amine is pyrrolidine;, '(A) contacting, in a reaction zone, a first mixture with a second mixture'}{'sub': '2', 'claim-text': (1) a pressure from about 100 Pascals (Pa) to about 120,000 Pa, and', '(2) a temperature below about the thermal decomposition temperature of said enamine during said reacting; and, '(B) reacting in said reaction zone said amine and said carbonyl to produce an enamine and HO, wherein said enamine is 1-(3-methylsulfanyl-but-1-enyl)-pyrrolidine, and wherein reacting is conducted under azeotropic distillation conditions comprising'}{'sub': '2', '(C) removing a vapor phase comprising said toluene, amine, and HO; and'}(D) condensing said vapor phase from step (C) to produce a condensate; and{'sub': '2', '(E) contacting said condensate from step (D) with a recovery mixture comprising HO, toluene, amine, and sodium hydroxide to produce a separate mixture comprising said amine and said toluene, and another mixture comprising H2O and sodium hydroxide; and'}(F) optionally, returning said mixture comprising amine and toluene from step (E) back to said reaction zone;wherein said process no desiccants are used to remove water andwherein said process the molar ratio of amine to carbonyl is greater than 1 but less than about 1.1.. A process to produce 1-(3-methylsulfanyl-but-1-enyl)-pyrrolidine said process comprising: This Application is a continuation of U.S. non-provisional application Ser. No. 13/303,187, which was filed on 23 Nov. 2011, and claims priority from, and benefit of U.S. provisional application 61/419,296, filed on Dec. 3, 2010. The entire contents of these application are hereby incorporated by reference into this Application.The invention ...

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22-03-2018 дата публикации

(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS

Номер: US20180079709A1
Принадлежит:

The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. 1140-. (canceled)141. A compound chosen from N-(4′-((trans)-2-((4-aminocyclohexyl)amino) cyclopropyl)-[1 ,1′-biphenyl]-3-yl)-2-cyanobenzenesulfonamide , an optically active stereoisomer thereof , and a salt or solvate thereof.142. The compound of claim 141 , wherein the compound is an optically active stereoisomer.143. The compound of claim 141 , wherein the compound is N-(4′-((trans)-2-((4-aminocyclohexyl)amino) cyclopropyl)-[1 claim 141 ,1′-biphenyl]-3-yl)-2-cyanobenzenesulfonamide or a pharmaceutically acceptable salt or solvate thereof.144. The compound of claim 141 , wherein the compound is a hydrochloride salt of N-(4′-((trans)-2-((4-aminocyclohexyl)amino) cyclopropyl)-[1 claim 141 ,1′-biphenyl]-3-yl)-2-cyanobenzenesulfonamide.145. A pharmaceutical composition comprising a compound chosen from N-(4′-((trans)-2-((4-aminocyclohexyl)amino)cyclopropyl)-[1 claim 141 ,1′-biphenyl]-3-yl)-2-cyanobenzenesulfonamide claim 141 , an optically active stereoisomer thereof claim 141 , and a pharmaceutically acceptable salt or solvate thereof claim 141 , and a pharmaceutically acceptable carrier.146. The pharmaceutical composition of claim 145 , wherein the compound is an optically active stereoisomer.147. The pharmaceutical composition of claim 145 , wherein the compound is N-(4′-((trans)-2-((4-aminocyclohexyl)amino)cyclopropyl)-[1 claim 145 ,1′-biphenyl]-3-yl)-2-cyanobenzenesulfonamide or a pharmaceutically acceptable salt or solvate thereof.148. The pharmaceutical composition of claim 145 , wherein the compound is a hydrochloride salt of N-(4′-((trans)-2-((4-aminocyclohexyl)amino)cyclopropyl)-[1 claim 145 ,1′-biphenyl]-3-yl)-2-cyanobenzenesulfonamide.149. A method of treating cancer ...

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24-03-2016 дата публикации

1-[2-(2,4-DIMETHYLPHENYLSULFANYL)-PHENYL]PIPERAZINE AS A COMPOUND With COMBINED SEROTONIN REUPTAKE, 5-HT3 AND 5-HT1A ACTIVITY FOR THE TREATMENT OF COGNITIVE IMPAIRMENT

Номер: US20160083359A1
Принадлежит:

1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine exhibits potent activity on SERT, 5-HTand 5-HTand may as such be useful for the treatment of cognitive impairment, especially in depressed patients. 1. 1-[2-(2 ,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrochloride salt with XRDP reflections at 9.41 , 12.37 , 19.66 and 22.55+/−0.10° (°2θ).2. A pharmaceutical composition claim 1 , comprising a compound according to together with a pharmaceutically acceptable excipient.3. The composition according to claim 2 , said composition being a tablet prepared by wet granulation and comprising anhydrous calcium hydrogen phosphate claim 2 , corn starch claim 2 , PVP-VA copolymer claim 2 , microcrystalline cellulose claim 2 , sodium starch glycolate claim 2 , talc and magnesium stearate.6. A method of treating a disease selected from the group consisting of affective disorders claim 1 , depression claim 1 , major depressive disorder claim 1 , postnatal depression claim 1 , depression associated with bipolar disorder claim 1 , Alzheimer's disease claim 1 , psychosis claim 1 , cancer claim 1 , age or Parkinson's disease claim 1 , anxiety claim 1 , general anxiety disorder claim 1 , social anxiety disorder claim 1 , obsessive compulsive disorder claim 1 , panic disorder claim 1 , panic attacks claim 1 , phobia claim 1 , social phobia claim 1 , agoraphobia claim 1 , stress urinary incontinence claim 1 , emesis claim 1 , IBS claim 1 , eating disorders claim 1 , chronic pain claim 1 , partial responders claim 1 , treatment resistant depression claim 1 , Alzheimer's disease claim 1 , cognitive impairment claim 1 , ADHD claim 1 , melancholia claim 1 , PTSD claim 1 , hot flushes claim 1 , sleep apnoea claim 1 , alcohol claim 1 , nicotine or carbohydrate craving claim 1 , and substance abuse and alcohol or drug abuse claim 1 , the method comprising administering a therapeutically effective amount of a compound according to to a patient in need thereof.9. The process according to claim ...

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12-06-2014 дата публикации

PHENYL-PIPERAZINE DERIVATIVES AS SEROTONIN REUPTAKE INHIBITORS

Номер: US20140163043A1
Принадлежит:

The invention provides compounds represented by the general formula I 115-. (canceled)17. The process of claim 16 , wherein each Ris independently trifluoromethyl or C-alkyl.18. The process of claim 16 , wherein each Ris independently halogen claim 16 , C-alkoxy claim 16 , C-alkylsulfanyl claim 16 , C-alkyl claim 16 , hydroxyl claim 16 , or trifluoromethyl.19. The process of claim 16 , wherein the compound of general formula I is 1-[2-(2 claim 16 ,4-dimethylphenylsulfanyl)phenyl]piperazine.20. 1-[2-(2 claim 16 ,4-Dimethylphenylsulfanyl)phenyl]piperazine or a pharmaceutically acceptable acid addition salt thereof obtained in the process of .21. A pharmaceutical composition claim 20 , comprising the compound of and at least one pharmaceutically acceptable carrier or diluent.22. A method for the treatment of an affective disorder in a living animal body claim 20 , comprising administering a therapeutically effective amount of the compound of .23. The method of claim 22 , wherein the living animal body is a human.24. The method of claim 22 , wherein the affective disorder is depression claim 22 , anxiety disorder claim 22 , or obsessive compulsive disorder.25. The method of claim 24 , wherein the anxiety disorder is general anxiety disorder or panic disorder.26. The method of claim 24 , wherein the affective disorder is depression. The present invention relates to novel compounds which are serotonin reuptake inhibitors and as such effective in the treatment of for example depression and anxiety.Selective serotonin reuptake inhibitors (hereinafter referred to as SSRIs) have become first choice therapeutics in the treatment of depression, certain forms of anxiety and social phobias, because they are effective, well tolerated and have a favourable safety profile compared to the classic tricyclic antidepressants.However, clinical studies on depression indicate that non-response to SSRIs is substantial, up to 30%. Another, often neglected, factor in antidepressant treatment ...

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30-03-2017 дата публикации

NEW VORTIOXETINE INTERMEDIATE AND SYNTHESIS PROCESS THEREOF

Номер: US20170088530A1
Принадлежит:

The present invention provides a new intermediate II and a method for synthesizing the same. The method comprises: (a) firstly diazotizing a compound of formula I as a raw material, and then halogenating to obtain an intermediate II; and (b) reacting the intermediate II with a compound III to obtain a compound IV, hydrolyzing the obtained compound IV directly without being separated to obtain Vortioxetine represented by compound V. The intermediate II can be used for synthesizing Vortioxetine. 2. The method of claim 1 , wherein R is selected from: tert-butoxycarbonyl claim 1 , 9-fluorenylmethoxycarbonyl claim 1 , carboxybenzyl claim 1 , acetyl or trifluoroacetyl.3. The method of claim 2 , wherein R is tert-butoxycarbonyl or acetyl.4. The method of claim 1 , wherein X is selected from: chlorine claim 1 , bromine or iodine.5. The method of claim 4 , wherein X is bromine.6. The method of claim 1 , wherein the halogenating agent used in the halogenating reaction is selected from: NaX claim 1 , KX claim 1 , LiX claim 1 , MgX claim 1 , CuX claim 1 , CuX claim 1 , or a mixture of any two thereof claim 1 , or a mixture of copper sulfate and NaX.7. The method of claim 6 , wherein the halogenating agent is a mixture of sodium bromide and cuprous bromide claim 6 , or a mixture of lithium bromide and cuprous bromide.10. The compound of claim 9 , wherein X is selected from: chlorine claim 9 , bromine or iodine.11. The compound of claim 10 , wherein X is bromine.13. The method of claim 12 , wherein the obtained compound IV is hydrolyzed directly without being separated to obtain Vortioxetine represented by compound V.14. The method of claim 12 , wherein the molar ratio of bis(2-diphenylphosphinophenyl)ether to the intermediate II is 0.6 to 6.0%.15. The method of claim 13 , wherein the molar ratio of bis(2-diphenylphosphinophenyl)ether to the intermediate II is 0.6 to 6.0%.16. The method of claim 12 , wherein the molar ratio of bis(2-diphenylphosphinophenyl)ether to the ...

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02-04-2015 дата публикации

COMPOUNDS AND METHODS FOR TREATING MALARIA

Номер: US20150094294A1
Принадлежит:

The present disclosure provides compounds, specifically pyrimidin-4,6-dicarboxylic acid amide derivatives, or pharmaceutically acceptable salts thereof and pharmaceutical compositions containing said compounds. Also provided are methods for treating a mammal having malaria, or killing or inhibiting the growth of a species, comprising administering to said mammal or contacting said species with, an effective amount of a pyrimidin--dicarboxylic acid amide derivative. 1144-. (canceled)146. A pharmaceutical composition comprising a compound of claim 145 , or a pharmaceutically acceptable salt thereof claim 145 , and a pharmaceutically acceptable carrier.148. The method of wherein the malaria is chloroquine-sensitive or chloroquine-resistant. The present disclosure was supported by funds from the U.S. Government (NIH/NIAID Grant No. 1R44AI090762-01) and the U.S. Government may therefore have certain rights in the disclosure.The present disclosure is directed, in part, to compounds, and pharmaceutically acceptable salts thereof, and compositions thereof for treating a mammal having malaria, or killing or inhibiting the growth of a species.World-wide, 41% of the population live in areas where malaria is transmitted, such as parts of Africa, Asia, Middle East, Central and South America, Hispaniola, and Oceania. Each year between 350 and 500 million cases of malaria occur worldwide, and over one million people die, most of them young children in sub-Saharan Africa. In areas of Africa with high malaria transmission, an estimated 990,000 people died of malaria in 1995. In 2002, malaria was the fourth cause of death in children in developing countries. In addition, malaria caused 10.7% of all children's deaths in developing countries.Antimicrobial peptides (AMPs) represent a component of the innate immune system that provides resistance to a variety of pathogenic bacteria. AMPs have provided new leads for developing antibiotics, because they play a central role in the innate ...

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02-04-2015 дата публикации

LIQUID FORMULATIONS OF SALTS OF 1-[2-(2,4-DIMETHYLPHENYLSULFANYL)PHENYL]PIPERAZINE

Номер: US20150094316A1
Принадлежит:

Liquid formulations of lactic acid addition salts of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine are provided 1. A liquid pharmaceutical formulation comprising a salt of 1-[2-(2 ,4-dimethylphenylsulfanyl)phenyl]piperazine , the salt being a DL-lactic acid addition salt , a L-lactic acid addition salt , or a D-lactic acid addition salt.2. The liquid formulation of claim 1 , wherein the salt is the DL-lactic acid addition salt.3. The liquid formulation of claim 1 , wherein the salt is the L-lactic acid addition salt.4. The liquid formulation of claim 1 , wherein the salt is the D-Lactic acid addition salt.5. The liquid formulation of claim 1 , wherein the concentration of the salt is at least 2.5 mg/mL.6. A method for the treatment of a disease selected from mood disorders; major depressive disorder; general anxiety disorder; panic disorder; post traumatic stress disorder; depression associated with cognitive impairment claim 1 , Alzheimer's disease or anxiety; depression with residual symptoms; chronic pain; eating disorder or abuse claim 1 , said method comprising the administration of a therapeutically effective amount of the liquid formulation of to a patient in need thereof.7. The method of claim 6 , wherein a predetermined volume of the liquid formulation is measured out and the resulting volume added to a liquid claim 6 , which liquid is administered orally to the patient.8. The method of claim 6 , wherein the salt is the DL-lactic acid addition salt.9. The method of claim 6 , wherein the salt is the L-lactic acid addition salt.10. The method of claim 6 , wherein the salt is the D-Lactic acid addition salt.11. The method of claim 6 , wherein the concentration of the salt is at least 2.5 mg/mL.12. A container fitted with a drop aggregate claim 1 , which container comprises the liquid formulation of .13. The container of claim 12 , wherein the salt is the DL-lactic acid addition salt.14. The container of claim 12 , wherein the salt is the L-lactic acid ...

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19-03-2020 дата публикации

APPLICATION OF 5-HT6 RECEPTOR ANTAGONISTS FOR THE ALLEVIATION OF COGNITIVE DEFICITS OF DOWN SYNDROME

Номер: US20200085819A1

Methods for treating Down syndrome and improving cognitive function of a patient with an intellectual disability are disclosed. 5-hydroxytryptamine sub-receptor six (5-HT) receptor antagonists are provided for improving the cognition of a Down syndrome patient. 1. A method of improving cognitive function in a subject with Down syndrome , comprising administering to the subject a 5-HTreceptor antagonist in an amount sufficient for a therapeutic effect by binding to a 5-HTreceptor , wherein the subject has chronic cognitive impairment caused by a genetic anomaly.2. The method of claim 1 , where the 5-HTreceptor antagonist is chosen from: a 5-HTreceptor inverse agonist claim 1 , a 5-HTreceptor competitive antagonist claim 1 , or a 5-HTreceptor inhibitor.3. The method of claim 2 , wherein the 5-HTreceptor antagonist is a 5-HTreceptor competitive antagonist.4. The method of claim 1 , wherein the 5-HTreceptor antagonist directly binds to the 5-HTreceptor.5. The method of claim 1 , wherein the 5-HTreceptor antagonist is a small molecule 5-HTreceptor antagonist.6. The method of claim 5 , wherein the small molecule 5-HTreceptor antagonist has a molecular weight of less than 800 Daltons.8. The method of claim 1 , wherein the subject is administered a pharmaceutical composition comprising a 5-HTreceptor antagonist or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.9. The method of claim 1 , wherein the route of administration of the 5-HTantagonist is selected from at least one of the following: intravenous claim 1 , intraperitoneal claim 1 , subcutaneous claim 1 , parenteral claim 1 , intramuscular claim 1 , oral claim 1 , topical claim 1 , transmucosal claim 1 , intraventricular claim 1 , or intrathecal administration.10. The method of claim 1 , wherein the subject suffers from a comorbid disorder associated with Down syndrome comprising Autism spectrum disorders claim 1 , attention deficit hyperactivity disorder claim 1 , ...

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05-05-2022 дата публикации

CRYSTALLINE PPAR-DELTA AGONIST

Номер: US20220135532A1
Принадлежит:

Described herein is crystalline sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate, uses of such crystalline material in the preparation of pharmaceutical compositions for the treatment of diseases or conditions that would benefit by administration with a PPARδ agonist compound.

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19-03-2020 дата публикации

N-HYDROXYLSULFONAMIDE DERIVATIVES AS NEW PHYSIOLOGICALLY USEFUL NITROXYL DONORS

Номер: US20200087253A1
Принадлежит:

The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release HNO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives. 2. The method of claim 1 , wherein claim 1 , in the compound of formula (III) claim 1 , each Ris independently selected from F claim 1 , Br claim 1 , Cl claim 1 , CF claim 1 , phenyl claim 1 , methyl claim 1 , SONHOH claim 1 , and C(O)O(C-C)alkyl.3. The method of claim 2 , wherein claim 2 , in the compound of formula (III) claim 2 , Ris methyl and ring C is furan.5. The method of claim 4 , wherein claim 4 , in the compound of formula (III) claim 4 , Ris methyl and ring C is furan. This application claims priority to U.S. Provisional Patent Application Ser. No. 60/783,556, filed Mar. 17, 2006 and entitled “N-Hydroxylsulfonamide Derivatives as New Physiologically Useful Nitroxyl Doners,” which is incorporated herein by reference in its entirety.This invention was made in part with government support under Grant No. CHE-0518406 from the National Science Foundation. The government may have certain rights in this invention.Congestive heart failure (CHF) is a generally progressive, life threatening condition in which myocardial contractility is depressed such that the heart is unable to adequately pump the blood returning to it, also referred to as decompensation. Symptoms include breathlessness, fatigue, weakness, leg swelling, and exercise intolerance. On physical examination, patients with heart failure often have elevated heart and respiratory rates (an indication of fluid in the lungs), edema, jugular venous distension, ...

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19-03-2020 дата публикации

Complexes

Номер: US20200087332A1
Принадлежит:

The present invention provides a palladium(II) complex of formula (1) or a palladium(II) complex of formula (2). 2. The process of claim 1 , wherein E is P.3. The process of claim 2 , wherein Rand Rare less sterically bulky than a cyclohexyl group when R claim 2 , R claim 2 , R claim 2 , Rand/or Rare more sterically bulky than a cyclohexyl group.4. The process of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare —H.5. The process of claim 1 , wherein two of R claim 1 , R claim 1 , Rand Rare —H claim 1 , and the other two of R claim 1 , R claim 1 , Rand Rare claim 1 , independently claim 1 , unsubstituted straight-chain alkyl claim 1 , unsubstituted branched-chain alkyl claim 1 , unsubstituted cycloalkyl claim 1 , or unsubstituted alkoxy.6. The process of claim 1 , wherein three of R claim 1 , R claim 1 , R claim 1 , Rand Rare —H claim 1 , and the other two of R claim 1 , R claim 1 , R claim 1 , Rand Rare claim 1 , independently claim 1 , unsubstituted straight-chain alkyl claim 1 , unsubstituted branched-chain alkyl claim 1 , unsubstituted cycloalkyl claim 1 , unsubstituted alkoxy claim 1 , unsubstituted —N(alkyl) claim 1 , wherein the alkyl groups are independently straight-chain or branched-chain groups claim 1 , or unsubstituted —N(aryl) claim 1 , wherein the aryl groups are the same or different; or{'sub': 7', '8', '9', '10', '11', '7', '8', '9', '10', '11', '2', '2, 'wherein two of R, R, R, Rand Rare —H, and the other three of R, R, R, Rand Rare, independently, unsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted —N(alkyl), wherein the alkyl groups are independently straight-chain or branched-chain groups, or unsubstituted —N(aryl), wherein the aryl groups are the same or different.'}8. The process according to claim 1 , wherein X is a halo group or a trifluoroacetate group.11. The process of claim 10 , wherein E is P.12. The process of claim 11 , wherein Rand Rare less ...

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21-04-2016 дата публикации

LIPIDS AND LIPID COMPOSITIONS FOR THE DELIVERY OF ACTIVE AGENTS

Номер: US20160106842A1
Принадлежит:

This invention provides for a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein R-R, L and X are defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues. 221-. (canceled)22. A lipid composition comprising a compound according to or a pharmaceutically acceptable salt thereof.23. The lipid composition according further comprising a biologically active agent.24. The lipid composition according wherein the biologically active agent is a siRNA.2530-. (canceled)31. A pharmaceutical composition comprising the lipid composition according to and a pharmaceutically acceptable carrier or excipient.32. A method for the treatment of a disease or condition comprising administering a therapeutically effective amount of the lipid composition according to to a patient in need of treatment thereof.33. A method for the treatment of a disease or condition comprising administering a therapeutically effective amount of the pharmaceutical composition according to .34. The lipid composition according to wherein the biologically active agent is an mRNA.3540-. (canceled)41. A pharmaceutical composition comprising the lipid composition according to and a pharmaceutically acceptable carrier or excipient.42. A method for the treatment of a disease or condition comprising administering a therapeutically effective amount of the lipid composition according to to a patient in need of treatment thereof.43. A method for the treatment of a disease or condition comprising administering a therapeutically effective amount of the pharmaceutical composition according to .44. A compound according to which is:1-(3,5-bis((Z)-octadec-9-en-1-yloxy)phenyl)-N,N-dimethylmethanamine;1-(3,5-bis((9Z,12Z)-octadeca-9,12-dien-1-yloxy)phenyl)-N,N-dimethylmethanamine;2,2′-((3,5-bis((9Z,12Z)-octadeca-9,12-dien-1-yloxy)benzyl)azanediyl)diethanol;1-(3,5-bis((9Z,12Z)- ...

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04-04-2019 дата публикации

HETEROCYCLIC SULFONAMIDES, USES AND PHARMACEUTICAL COMPOSITIONS THEREOF

Номер: US20190100491A1
Принадлежит:

The invention is directed to a class of compounds, including the pharmaceutically acceptable salts of the compounds, having the structure of formula I: 1. (canceled)4. The method according to claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein “Z” is —O—.5. The method according to claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein X is —O—.6. The method according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein ring “A” is phenyl.7. The method according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein ring “A” is phenyl; n is zero claim 6 , one or two; Ris selected from the group consisting of hydrogen claim 6 , halogen claim 6 , hydroxyl claim 6 , —CF claim 6 , —CN claim 6 , —(C═O)R claim 6 , —O—(C═O)—R claim 6 , —(NR)—(C═O)—R claim 6 , —(C═O)—OR claim 6 , —(C═O)—N(R) claim 6 , —OR claim 6 , —O—(C═O)—OR claim 6 , —O—(C═O)—N(R) claim 6 , —NO claim 6 , —N(R) claim 6 , —(NR)—SO—R claim 6 , —S(O)R claim 6 , —SO—N(R) claim 6 , and (C-C)alkyl; wherein said (C-C)alkyl is optionally substituted with one claim 6 , two claim 6 , three or four R.8. The method according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein ring “A” is (C-C)heteroaryl; n is zero claim 5 , one or two; and wherein Ris selected from the group consisting of hydrogen claim 5 , halogen claim 5 , hydroxyl claim 5 , —CF claim 5 , —CN claim 5 , —(C═O)R claim 5 , —O—(C═O)—R claim 5 , —(NR)—(C═O)—R claim 5 , —(C═O)—OR claim 5 , —(C═O)—N(R) claim 5 , —OR claim 5 , —O—(C═O)—OR claim 5 , —O—(C═O)—N(R) claim 5 , —NO claim 5 , —N(R) claim 5 , —(NR)—SO—R claim 5 , —S(O)R claim 5 , —SO—N(R) claim 5 , and (C-C)alkyl; wherein said (C-C)alkyl is optionally substituted with one claim 5 , two claim 5 , three or four R.9. The method according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein ring “A” is (C-C)heterocycloalkyl; n is zero claim 5 , one or two; and wherein ...

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03-07-2014 дата публикации

MODULATORS OF THE NUCLEAR HORMONE RECEPTOR ROR

Номер: US20140187554A1
Принадлежит: The Scripps Research Institute

The invention provides small molecule modulators of retinoic acid receptor-related orphan receptors such as RORα, RORβ, or RORγ. Compounds of the invention can be effective modulators at concentrations ineffective to act on LXR receptors, or on other nuclear receptors, or other biological targets. Methods of modulation the RORs and methods of treating metabolic disorders, immune disorders, cancer, and CNS disorders wherein modulation of an ROR is medically indicated are also provided. 2. The compound of formula (I) of wherein X is CH claim 1 , N claim 1 , or O.3. The compound of formula (I) of wherein Y is NH claim 1 , N—(C1-C4)alkyl claim 1 , N—(C1-C4)hydroxyalkyl claim 1 , N-phenyl claim 1 , N—(C1-C4)alkanoyl claim 1 , N-benzyl claim 1 , N-biphenylmethyl claim 1 , N-heteroarylmethyl claim 1 , N-heterocyclylmethyl claim 1 , or Y is N—C(O)Rwherein Ris NH—(C1-C4)alkyl claim 1 , NH-phenyl claim 1 , or NH-benzyl; wherein any Y can be substituted or unsubstituted.4. The compound of formula (I) of wherein Y is any of CHOH claim 1 , NH claim 1 , NCHCH claim 1 , NCHCHOH claim 1 , NCH(CH) claim 1 , NCOCH claim 1 , N CH claim 1 , N—CH-biphenyl-4′-C(CF)OH claim 1 , N—CH-benzo[1 claim 1 ,3]dioxole claim 1 , N—CH—CH-3-CF claim 1 , N—CH—CH-3-OCH claim 1 , N—CH—CH-Ph. N—CH—CH-4-Br. N—CH-Ph claim 1 , N—CH-pyridin-4-yl claim 1 , N—CH-thiophen-2-yl claim 1 , N—CH-5-fluoro-1H-indol-2-yl claim 1 , N—CH-2 claim 1 ,3-dihydro-1 claim 1 ,4-benzodioxin-2-yl claim 1 , N—CO—C—(CH) claim 1 , N—CO-tetrahydrofuran-2-yl claim 1 , N—CO—CHCH claim 1 , N—CO—NH—CH—CH—CH claim 1 , N—CO—NH-Ph claim 1 , or N—CO—NH—CH-Ph.5. The compound of formula (I) of wherein Ris OH claim 1 , (C1-C4)alkyl claim 1 , (C1-C4)fluoroalkyl substituted with OH claim 1 , NHC(O)—(C1-C4)alkyl claim 1 , NHC(O)-aryl claim 1 , NHC(O)-heteroaryl claim 1 , HN—SO-aryl claim 1 , HN—SO-alkylaryl claim 1 , SONRwherein R is as defined in claim 1 , C(O)O—(C1-C4)alkyl claim 1 , C(O)NH-aryl claim 1 , C(O)NH-alkylaryl claim 1 , or C(O)NH- ...

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03-07-2014 дата публикации

ANTI-AMYLOID COMPOUNDS AND METHODS

Номер: US20140187556A1
Принадлежит: Treventis Corporation

Anti-amyloid compounds are provided along with methods of use thereof. 2. The compound of in which the compound is according to Formula Ia.3. The compound of in which the compound is according to Formula Ib.4. The compound of in which the compound is according to Formula Ic.5. The compound of in which the compound is according to Formula Id.6. The compound of in which the compound is according to Formula Ie.7. The compound of in which the compound is according to Formula If.8. The compound of in which E is carbon.9. The compound of in which E is nitrogen.10. The compound of in which Ris nitro and Ris selected from the group consisting of ethanol-1-yl claim 3 , methanol claim 3 , 2 claim 3 ,2 claim 3 ,2-trifluoro-1-hydroxyethanol-1-yl claim 3 , and 2 claim 3 ,2 claim 3 ,2-trifluoroethanol-1-yl.11. The compound of in which the compound is 1-(3′-(benzylamino)-4′-nitro-[1 claim 10 ,1′-biphenyl]-3-yl)-2 claim 10 ,2 claim 10 ,2-trifluoroethanol.12. The compound of in which the compound is 1-(3′-(benzylamino)-4′-nitro-[1 claim 10 ,1′-biphenyl]-3-yl)-2 claim 10 ,2 claim 10 ,2-trifluoroethane-1 claim 10 ,1-diol.13. The compound of in which Ris nitro and Ris C-linked tetrazole.14. The compound of in which Ris nitro.15. The compound of in which Ris selected from the group consisting of sulfonamide claim 14 , alkylamide claim 14 , dialkylamide claim 14 , benzyl alkylamide claim 14 , N-pyrrolidinamide claim 14 , (N′-methanonylpiperazine)amide claim 14 , (N′-methylpiperazine)amide claim 14 , morphilinamide claim 14 , and piperidineamide.16. The compound of claim 1 , wherein compound inhibits the aggregation of an amyloidogenic protein.17. The compound of for use in the preparation of a pharmaceutically effective dosage form the treatment of amyloid diseases.18. The compound of claim 16 , wherein said amyloid disease is selected from the group consisting of Alzheimer's disease claim 16 , Parkinson's disease claim 16 , Huntington's disease claim 16 , and prion diseases.19. A ...

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03-07-2014 дата публикации

BENZOCYCLOHEPTANE AND BENZOXEPINE DERIVATIVES

Номер: US20140187557A1
Принадлежит: Janssen Pharmaceutica NV

The present invention relates to a compound of formula (I) 2. The method as claimed in wherein A represents phenyl or phenyl substituted with 1 claim 1 , 2 or 3 Rsubstituents.4. The method as claimed in wherein A represents pyridyl claim 1 , pyrimidinyl or quinolinyl claim 1 , each of said pyridyl claim 1 , pyrimidinyl or quinolinyl optionally being substituted with 1 claim 1 , 2 or 3 Rsubstituents.5. The method as claimed in wherein Z represents CH.6. The method as claimed in wherein Z represents O.7. The method as claimed in wherein Rrepresents halo claim 1 , hydroxyl claim 1 , Calkyl or Calkyloxy.8. The method as claimed in wherein Rrepresents hydrogen.11. The method as claimed in wherein n represents an integer of value 1 or 2.12. The method as claimed in wherein n is 0.13. The method as claimed in wherein A represents phenyl claim 1 , 1 claim 1 ,3-benzodioxolyl claim 1 , 2 claim 1 ,3-dihydro-1 claim 1 ,4-benzodioxinyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , quinolinyl; each of said rings optionally being substituted with 1 or 2 substituents each independently selected from halo claim 1 , hydroxyl claim 1 , Calkyl or Calkyloxy; Rand Reach independently represent hydrogen claim 1 , Calkyl claim 1 , CalkyloxyCalkyl claim 1 , phenylCalkyl; or Rand Rare taken together with the nitrogen to which they are attached to form pyrrolidinyl optionally substituted in position 3 with hydroxyl; piperidinyl; morpholinyl; piperazinyl optionally substituted with Calkyl or Calkylcarbonyl; Rrepresents hydrogen or methyl.14. The method as claimed in wherein the substituents on the cycloheptane or oxepine ring have a cis configuration.15. The method as claimed in wherein the compound is an enantiomeric pure form.16. The method as claimed in wherein the compound is selected from(±) cis-6-(4-Chloro-3-methoxy-phenyl)-5-(3-diethylamino-propyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol oxalate;(±) cis-6-(3-Chloro-phenyl)-5-(3-diethylamino-propyl)-6,7,8,9-tetrahydro-5H- ...

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27-04-2017 дата публикации

PROCESS FOR THE PREPARATION OF VORTIOXETINE SALTS

Номер: US20170114034A1
Принадлежит: EGIS GYOGYSZERGYAR ZRT.

The invention relates to an improved process for the preparation of pharmaceutical active ingredients and also to high purity salts and pharmaceutical compositions prepared by said process. More particularly the invention relates to an economical process for the preparation of the compound having the international non-proprietary name (INN) vortioxetine and the chemical nomenclature 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine. Vortioxetine corresponds to the following Formula 2. Process according to which comprisescarrying out the reaction of the compounds of the Formulae V and VI in a solvent, preferably an aprotic solvent;and/orusing as aprotic solvent an aromatic or aliphatic hydrocarbon, an ether, an acid amide, an urea derivative, a nitrile, an ester or a mixture thereof;and/or{'sub': '1-4', 'using as aprotic solvent an aromatic solvent, preferably toluene, xylene, ethyl benzene; an aliphatic solvent preferably pentane, hexane, cyclohexane, octane or petrolether; an ether preferably an aliphatic or cyclic ether, more advantageously diethyl ether, diisopropyl ether, dibutyl ether, methyl tert.butyl ether, diethylene glycol dimethyl ether or diethylene glycol monoethyl ether; an acid amide preferably dimethyl- or diethyl-formamide, dimethyl- or diethyl-acetamide or -propionamide; an urea derivative preferably 1,3-dimethyl-2-imidazolidinone (DMI); an ester preferably esters of acetic acid or propionic acid formed with Calcohols, preferably ethyl acetate, propyl acetate, ethyl propionate, butyl acetate or a mixture of said solvents;'}and/orusing as solvent a mixture of an aromatic solvent and an amide type solvent, preferably a mixture of toluene and DMI, whereby the ratio of toluene and DMI is 5:1-1:5, preferably 2:1-1:2, more advantageously 1:1.35-. (canceled)6. Process according to which comprisescarrying out the reaction of the compounds of the Formulae V and VI in the presence of an organic or inorganic base;and optionallycomprises using an organic ...

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18-04-2019 дата публикации

SPHINGOSINE KINASE TYPE 1 INHIBITORS AND USES THEREOF

Номер: US20190111007A1
Принадлежит:

Provided are inhibitors of sphingosine kinase Type I and their use in the treatment of asthma, among other indications and diseases. 5. The method of claim 4 , wherein R is a straight carbon chain claim 4 , a branched carbon chain claim 4 , a straight carbon chain comprising one or more heteroatoms claim 4 , a branched carbon chain comprising one or more heteroatoms claim 4 , a cyclic ring claim 4 , a heterocyclic ring claim 4 , an aromatic ring claim 4 , a hetero-aromatic ring claim 4 , or any combination of the foregoing.6. The method of claim 5 , wherein R is a straight carbon chain claim 5 , a branched carbon chain claim 5 , a straight carbon chain comprising one or more heteroatoms claim 5 , a branched carbon chain comprising one or more heteroatoms claim 5 , a cyclic ring claim 5 , a heterocyclic ring claim 5 , an aromatic ring claim 5 , or a hetero-aromatic ring.7. The method of claim 6 , wherein R is a straight carbon chain claim 6 , a branched carbon chain claim 6 , a straight carbon chain comprising one or more heteroatoms claim 6 , or a branched carbon chain comprising one or more heteroatoms.8. The method of claim 7 , wherein R is a straight carbon chain or a branched carbon chain.9. The method of claim 8 , wherein R is a straight carbon chain. This application is a continuation of U.S. application Ser. No. 15/954,131 filed Apr. 16, 2018, which is a continuation of U.S. application Ser. No. 15/181,826 filed Jun. 14, 2016 (now U.S. Pat. No. 9,974,758), which is a continuation of U.S. application Ser. No. 13/649,221 filed Oct. 11, 2012 (now U.S. Pat. No. 9,388,121), which is a divisional of U.S. application Ser. No. 12/584,131 filed Aug. 31, 2009 (now U.S. Pat. No. 8,314,151), which is a continuation-in-part of U.S. application Ser. No. 12/387,228 filed Apr. 29, 2009 (now U.S. Pat. No. 8,372,888), which claims the benefit of U.S. Provisional Application No. 61/048,638 filed Apr. 29, 2008, the contents of all of which are hereby incorporated by reference in ...

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25-04-2019 дата публикации

COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY

Номер: US20190119203A1
Принадлежит:

In one aspect, compounds of Formulae (I) and (II), or pharmaceutically acceptable salts thereof, are featured: Formulae (I) and (II), wherein the variables shown in Formulae (I) and (II) can be as defined anywhere herein. 4. The compound of any one of - , wherein Ris C(R)OH.5. The compound of any one of - , wherein Ris CN.6. The compound of any one of - , wherein Ris Cl.7. The compound of any one of - , wherein Ris F.8. The compound of any one of - , wherein R is pyridyl.9. The compound of any one of - , wherein R is morpholinyl.10. The compound of any one of - , wherein R is C-Ccycloalkyl.12. The compound of any one of , , or , wherein Z is N.13. The compound of any one of , , or , wherein Z is CH.14. The compound of any one of , , or - , wherein R is H.16. The compound of any one of , , or , wherein R is F.19. The compound of any one of , , , or , wherein:{'sup': 2″', '3″', '4″', '5″, 'R and R, taken together with the carbons connecting them form a five membered ring A and R and R, taken together with the carbons connecting them form a five-membered ring B;'}ring A is a saturated carbocyclic ring;ring B is a saturated carbocyclic ring;n1 is 3;n2 is 3;{'sup': '6', 'Ris H.'}20. The compound of any one of , , or - , wherein R is F.22. The compound of any one of , , , or , wherein R is H or F , and R is H.23. The compound of any one of , , , , or , wherein R is H.24. The compound of any one of , , , , or , wherein R is CN.25. The compound of any one of , , , , or , wherein R is CONH.26. The compound of any one of , , , , or , wherein R is COCH28. The compound of any one of or , wherein R is acetyl.29. The compound of any one of , , or , wherein R is F.30. The compound of any one of or - , wherein Ris H.31. The compound of any one of - , wherein Xis NH.32. The compound of any one of - or - , wherein Rand Rare each isopropyl.33. The compound of any one of - or - , wherein Rand Rare each H.34. The compound of any one of - or - , wherein:{'sup': 2', '3', '4', '5, 'Rand R, ...

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10-05-2018 дата публикации

Phenyl-Piperazine Derivatives As Serotonin Reuptake Inhibitors

Номер: US20180127389A1
Принадлежит:

The invention provides compounds represented by the general formula I 2. The compound according to claim 1 , provided that the compound is not 1-(2-phenoxyphenyl)piperazine.3. The compound according to claim 1 , provided that the compound is not 1-[2-(2-Methoxyphenoxy)phenyl]piperazine claim 1 , 1-[2-(2 claim 1 ,6-dimethoxyphenoxy)phenyl]-[1 claim 1 ,4]-diazepane claim 1 , 1-{2-[3-(dimethylamino)phenoxy]phenyl}piperazine claim 1 , 1-[2-(4-methylphenoxy)phenyl]piperazine claim 1 , 1-[2-(3-methylphenoxy)phenyl]piperazine claim 1 , 1-[2-(3-chlorophenoxy)phenyl]piperazine claim 1 , 1-[2-(3-methoxyphenoxy)phenyl]piperazine and 1-(2-phenoxyphenyl)-piperazine.4. The compound according to claim 1 , wherein p is 0 claim 1 , 1 or 2.5. The compound according to claim 1 , wherein Ris C-alkyl.6. The compound according to claim 1 , wherein m is 1 or 2.7. The compound according to claim 1 , wherein q is 0 claim 1 , 1 or 2.8. The compound according to claim 1 , wherein Ris trifluoromethyl claim 1 , or C-alkyl.9. The compound according to claim 1 , wherein s is 1 or 2.10. The compound according to claim 1 , wherein Ris selected from the group consisting of halogen claim 1 , C-alkoxy claim 1 , C-sulfanyl claim 1 , C-alkyl claim 1 , hydroxy or trifluoromethyl.11. The compound according to claim 1 , said compound being1-[2-(2-Trifluoromethylphenylsulfanyl)phenyl]piperazine,1-[2-(4-Bromophenylsulfanyl)phenyl]piperazine,1-{2-[4-(Methylsulfanyl)phenylsulfanyl]phenyl}piperazine,1-[2-(4-Hydroxyphenylsulfanyl]phenyl}piperazine,1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(3,5-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(2,6-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(2,5-Dimethylphenylsulfanyl)phenyl]piperazine,1-[2-(2-Trifluoromethylphenylsulfanyl)phenyl][1,4]diazepane,1-[2-(3-Methylphenylsulfanyl)phenyl]-[1,4]-diazepane,1-[2-(4-Butylphenoxy)phenyl]piperazine,1-[2-(4-Methoxyphenoxy)phenyl]piperazine,2-(4-Methylphenylsulfanyl)phenyl-1-piperazine,1-[2-(4-Chlorophenylsulfanyl) ...

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03-06-2021 дата публикации

Complexes

Номер: US20210163516A1
Принадлежит:

The present invention provides a palladium(II) complex of formula (1). 2. A palladium(II) complex according to claim 1 , wherein Ris selected from the group consisting of substituted and unsubstituted straight-chain alkyl claim 1 , substituted and unsubstituted branched-chain alkyl claim 1 , substituted and unsubstituted cycloalkyl claim 1 , substituted and unsubstituted aryl claim 1 , and substituted and unsubstituted heteroaryl wherein the heteroatoms are independently selected from sulfur claim 1 , nitrogen and oxygen.3. A palladium(II) complex according to claim 1 , wherein X is a halo group or a trifluoroacetate group.6. A process for carrying out a carbon-carbon coupling reaction or a carbon-heteroatom coupling reaction in the presence of a catalyst claim 1 , the process comprising the use of a complex of formula (1) as defined in .7. The process of claim 6 , wherein the carbon-carbon coupling reaction is (a) a Heck reaction; (b) a Suzuki reaction; (c) a Sonogashira reaction; or (d) a Negishi reaction and the carbon-heteroatom coupling reaction is a Buchwald-Hartwig amination reaction. This application is a divisional of U.S. patent application Ser. No. 16/686,960, filed Nov. 18, 2019, which is a divisional of U.S. patent application Ser. No. 16/284,841, filed Feb. 25, 2019, now U.S. Pat. No. 10,858,382, which is a divisional of U.S. patent application Ser. No. 15/318,106, filed Dec. 12, 2016, now U.S. Pat. No. 10,253,056, which is a US national stage of International patent Application No. PCT/GB2015/050835, filed Mar. 20, 2015, which claims priority to U.S. Provisional Patent Application No. 62/011,168, filed Jun. 12, 2014, all applications of which are incorporated by reference herein.The present invention relates to optionally substituted π-allyl palladium complexes and their use thereof in coupling reactions.WO2011/161451 (to Johnson Matthey PLC) describes π-allyl complexes, such as π-allyl palladium complexes and π-allyl nickel complexes.Faller et al ( ...

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08-09-2022 дата публикации

BENZENESULFONAMIDE DERIVATIVES AND USES THEREOF

Номер: US20220281812A1
Принадлежит:

Provided herein are benzenesulfonamide derivatives having Formula (III), pharmaceutical compositions comprising said compounds, and method for using said compounds for disrupting proteins/polypeptides, protein/polypeptide function, and for the treatment of diseases through the disruption of proteins or polypeptides involved in the etiology of the disease. Said compounds comprise fluorinated benzene sulfonamide structures. 2. The compound of claim 1 , wherein Gis -L-G claim 1 , L is a nitrogen containing linker claim 1 , and G is an organic residue.3. The compound of claim 2 , L is —NR— claim 2 , —NR-(substituted or unsubstituted alkyl) claim 2 , —NR-(substituted or unsubstituted heteroalkyl) claim 2 , —NR-(substituted or unsubstituted cycloalkyl) claim 2 , —NR-(substituted or unsubstituted heterocycloalkyl) claim 2 , —NR-(substituted or unsubstituted aryl) claim 2 , or —NR-(substituted or unsubstituted heteroaryl); wherein{'sup': 5', '6', '6', '6, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '3', '5', '2', '4, 'Ris hydrogen, —CN, —C(═O)R, —C(═O)OR, substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Chaloalkyl, substituted or unsubstituted C-Cheteroalkyl, —C-Calkylene-OR, substituted or unsubstituted C-Ccycloalkyl, or substituted or unsubstituted C-Cheterocycloalkyl; and'}{'sup': '6', 'sub': 1', '4', '1', '4', '1', '4, 'Ris hydrogen, substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Cfluoroalkyl, or substituted or unsubstituted C-Cheteroalkyl.'}6. The compound of any one of - claim 2 , wherein Ris —OR claim 2 , —SR claim 2 , —OS(═O)R claim 2 , —N(R) claim 2 , —NRC(═O)R claim 2 , —NRC(═O)N(R) claim 2 , —OC(═O)R claim 2 , —OC(═O)OR claim 2 , —OC(═O)N(R) claim 2 , —NRC(═O)OR claim 2 , substituted or unsubstituted C-Calkyl (e.g. claim 2 , cycloalkyl-alkyl or heterocycloalkyl-alkyl) claim 2 , substituted or unsubstituted C-Chaloalkyl claim 2 , substituted or unsubstituted C-Cheteroalkyl claim 2 , substituted or unsubstituted C- ...

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26-05-2016 дата публикации

PROCESS FOR THE PREPARATION OF AN ANTIDEPRESSANT AND THE INTERMEDIATES THEREOF

Номер: US20160145224A1
Принадлежит: DIPHARMA FRANCIS S.R.L.

The present invention relates to a process for the preparation of 1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine of formula (I), also known as vortioxetine, salts thereof, and intermediates useful for its synthesis. 2. The process according to claim 1 , wherein in a compound of formula (IV) claim 1 , or a salt thereof claim 1 , both R substituents are the same.3. The process according to claim 1 , wherein the reaction of a compound of formula (IV) claim 1 , wherein each of R substituents is an aldehyde group —CHO claim 1 , with a compound of formula (V) is performed under reductive amination conditions claim 1 , in the presence of a reducing agent and a solvent.4. The process according to claim 3 , wherein the reducing agent is selected from NaCNBH claim 3 , NaB(OAc)H claim 3 , a homogenous or heterogeneous palladium (Pd) or platinum (Pt) metal based catalyst and molecular hydrogen claim 3 , and a homogeneous or heterogeneous palladium (Pd) or platinum (Pt) metal based catalyst and a hydrogen donor under hydrogen transfer conditions.5. The process according to claim 4 , wherein NaB(OAc)H is generated in situ from NaBHand acetic acid.7. The process according to claim 6 , wherein the hydride reducing agent is selected from NaBH4 and LiAlH4.9. The process according to claim 1 , wherein the reaction of a compound of formula (IV) claim 1 , wherein each of R claim 1 , being the same or different claim 1 , is a —CH2X group with a compound of formula (V) is performed under the reaction conditions of the alkylating reactions claim 1 , and claim 1 , if the case claim 1 , in the presence of a base and a solvent.10. The process according to claim 9 , wherein in a compound of formula (V) Z is H or benzyl.11. The process according to claim 9 , wherein in a compound of formula (V) Z is H claim 9 , that is ammonia claim 9 , and an excess of a compound of formula (V) is used with no need for an additional base.12. The process according to claim 9 , wherein the alkylation ...

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17-06-2021 дата публикации

SPHINGOSINE KINASE TYPE 1 INHIBITORS AND USES THEREOF

Номер: US20210177776A1
Принадлежит:

Provided are inhibitors of sphingosine kinase Type I that are useful in the treatment of neuropathic pain. 5. The method of claim 4 , wherein R is a straight carbon chain claim 4 , a branched carbon chain claim 4 , a straight carbon chain comprising one or more heteroatoms claim 4 , a branched carbon chain comprising one or more heteroatoms claim 4 , a cyclic ring claim 4 , a heterocyclic ring claim 4 , an aromatic ring claim 4 , a hetero-aromatic ring claim 4 , or any combination of the foregoing.6. The method of claim 5 , wherein R is a straight carbon chain claim 5 , a branched carbon chain claim 5 , a straight carbon chain comprising one or more heteroatoms claim 5 , a branched carbon chain comprising one or more heteroatoms claim 5 , a cyclic ring claim 5 , a heterocyclic ring claim 5 , an aromatic ring claim 5 , or a hetero-aromatic ring.7. The method of claim 6 , wherein R is a straight carbon chain claim 6 , a branched carbon chain claim 6 , a straight carbon chain comprising one or more heteroatoms claim 6 , or a branched carbon chain comprising one or more heteroatoms.8. The method of claim 7 , wherein R is a straight carbon chain or a branched carbon chain.9. The method of claim 8 , wherein R is a straight carbon chain. This application is a continuation of U.S. application Ser. No. 16/813,961 filed Mar. 10, 2020, which is a continuation of U.S. application Ser. No. 16/572,699 filed Sep. 17, 2019, which is a continuation of U.S. application Ser. No. 16/199,337 filed Nov. 26, 2018 (now U.S. patent Ser. No. 10/456,370), which is a continuation of U.S. application Ser. No. 15/954,131 filed Apr. 16, 2018, (now U.S. Pat. No. 10,166,204), which is a continuation of U.S. application Ser. No. 15/181,826 filed Jun. 14, 2016 (now U.S. Pat. No. 9,974,758), which is a continuation of U.S. application Ser. No. 13/649,221 filed Oct. 11, 2012 (now U.S. Pat. No. 9,388,121), which is a divisional of U.S. application Ser. No. 12/584,131 filed Aug. 31, 2009 (now U.S. Pat. ...

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21-08-2014 дата публикации

PIPERAZINE DERIVATIVES, METHODS FOR PREPARING SAME, AND USES THEREOF IN THE TREATMENT OF INSULIN RESISTANCE

Номер: US20140235650A1
Принадлежит: Metabolys

The invention relates to a compound of formula (I), where R, R, R, m, n, and Lare as defined in claim , and to the methods for preparing same, to the pharmaceutical compositions containing same, and to the uses thereof in the treatment of diseases associated with insulin resistance syndrome. 2. Compound according to claim 1 , for which the carbocycle claim 1 , substituted or non-substituted claim 1 , is in 6 aromatic members claim 1 , the polycarbocycle claim 1 , substituted or non-substituted claim 1 , is in 9 or 10 members claim 1 , the heterocycle claim 1 , substituted or non-substituted claim 1 , is in 5 or 6 members and comprises 1 claim 1 , 2 or 3 heteroatoms claim 1 , the polyheterocycle claim 1 , substituted or non-substituted claim 1 , is in 9 or 10 members and comprises 1 claim 1 , 2 or 3 hetero atoms.3. Compound according to claim 1 , for which the carbocycles claim 1 , polycarbocycles claim 1 , heterocycles and polyheterocycles are non-substituted or substituted by one or more substituents claim 1 , identical or different claim 1 , chosen from:{'sub': 1', '6, 'a Cto Calkoxy group, linear or branched;'}a halogen atom;{'sub': 1', '5, 'a Cto Clinear or branched hydrocarbon group;'}{'sub': 1', '5, 'a Cto Clinear or branched hydrocarbon group, substituted by one or more halogen atoms;'}a cyano group (—CN);a carbocycle group in 5, 6 or 7 members, saturated, partially unsaturated or aromatic, substituted or non-substituted; or{'sub': 2', '1', '5, 'a sulfonylalkyl group (—S(O)-alkyl), in which the alkyl is linear or branched, Cto C.'}6. Compound according to claim 1 , in which R claim 1 , Reach represents a hydrogen atom and Rand R claim 1 , identical or different claim 1 , represent:a hydrogen atom;{'sub': 1', '5, 'a Cto Clinear or branched alkyl group;'}a carbocycle in 5, 6 or 7 members, saturated, partially unsaturated or aromatic; or{'sup': 3', '4, 'Rand Rform together with the carbon atom to which they are bonded a carbo cycle in 5, 6 or 7 members, ...

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04-09-2014 дата публикации

1-[2-(2,4-Dimethylphenylsulfanyl)-Phenyl]Piperazine As A Compound With Combined Serotonin Reuptake, 5-HT3 And 5-HT1a Activity For The Treatment Of Cognitive Impairment

Номер: US20140248355A1
Принадлежит: H. Lundbeck A/S

1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine exhibits potent activity on SERT, 5-HTand 5-HTand may as such be useful for the treatment of cognitive impairment, especially in depressed patients. 114-. (canceled)15. A method of curative treating a disease selected from the group consisting of affective disorders , depression , major depressive disorder , anxiety , general anxiety disorder , social anxiety disorder , obsessive compulsive disorder , panic disorder , and panic attacks , the method comprising administering a therapeutically effective amount of Compound I to patient in need thereof , wherein Compound I is crystalline 1-[2-(2 ,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt characterized by XRPD reflections at 6.89 , 9.73 , 13.78 and 14.64+/−0.10° 2θ.1643-. (canceled)44. The method of claim 15 , wherein the hydrobromide salt is characterized by an XRPD as shown in .45. The method of claim 15 , wherein Compound I has a particle size distribution corresponding to:D98%: 650-680 μm; D50%: 230-250 μm; and D5%: 40-60 μm;D98%: 370-390 μm; d50%: 100-120 μm; and D5%: 5-15 μm;D98%: 100-125 μm; D50%: 15-25 μm; and D5%: 1-3 μm; orD98%: 50-70 μm; D50%: 3-7 μm; and D5%: 0.5-2 μm.46. The method of claim 15 , wherein the disease is major depressive disorder. This is a divisional application of U.S. application Ser. No. 12/301,061, filed Nov. 17, 2008, which is a U.S. National Phase application under 35 U.S.C. §371 of International Patent Application No. PCT/DK2007/050075, filed Jun. 15, 2007, and claims the benefit of Danish Patent Application No. PA 2006 00824, filed Jun. 16, 2006; U.S. Provisional Application No. 60/805,014, filed Jun. 16, 2006; Danish Patent Application No. PA 2006 01223, filed Sep. 22, 2006; U.S. Provisional Application No. 60/826,666, filed Sep. 22, 2006; Danish Patent Application No. PA 2006 01384, filed Oct. 25, 2006; U.S. Provisional Application No. 60/862,826, filed Oct. 25, 2006; and Danish Patent Application No. PA 2007 ...

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04-09-2014 дата публикации

1-[2-(2,4-Dimethylphenylsulfanyl)-Phenyl]Piperazine As A Compound With Combined Serotonin Reuptake, 5-HT3 And 5-HT1a Activity For The Treatment Of Cognitive Impairment

Номер: US20140248356A1
Принадлежит: H. Lundbeck A/S

1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine exhibits potent activity on SERT, 5-HTand 5-HTand may as such be useful for the treatment of cognitive impairment, especially in depressed patients. 114-. (canceled)15. A method of curative treating a disease selected from the group consisting of Alzheimer's disease , cognitive impairment , and attention deficit hyperactivity disorder (ADHD) , the method comprising administering a therapeutically effective amount of Compound I to patient in need thereof , wherein Compound I is 1-[2-(2 ,4-dimethylphenylsulfanyl)-phenyl]piperazine or a pharmaceutically acceptable salt thereof and is crystalline.1643-. (canceled)44. The method of claim 15 , wherein Compound I is a hydrobromide salt of 1-[2-(2 claim 15 ,4-dimethylphenylsulfanyl)-phenyl]piperazine.45. The method of claim 44 , wherein the hydrobromide salt is characterized by XRPD reflections at 6.89 claim 44 , 9.73 claim 44 , 13.78 and 14.64+/−0.10° 2θ.46. The method of claim 45 , wherein the hydrobromide salt is characterized by an XRPD as shown in .47. The method of claim 45 , wherein Compound I has a particle size distribution corresponding to:D98%:650-680 μm; D50%:230-250 μm; and D5%:40-60 μm;D98%:370-390 μm; d50%:100-120 μm; and D5%:5-15 μm;D98%:100-125 μm; D50%:15-25 μm; and D5%:1-3 μm; orD98%:50-70 μm; D50%:3-7 μm; and D5%:0.5-2 μm.48. The method of claim 15 , wherein the disease is Alzheimer's disease.49. The method of claim 15 , wherein the disease is cognitive impairment.50. The method of claim 15 , wherein the disease is ADHD. This is a divisional application of U.S. application Ser. No. 12/301,061, filed Nov. 17, 2008, which is a U.S. National Phase application under 35 U.S.C. §371 of International Patent Application No. PCT/DK2007/050075, filed Jun. 15, 2007, and claims the benefit of Danish Patent Application No. PA 2006 00824, filed Jun. 16, 2006; U.S. Provisional Application No. 60/805,014, filed Jun. 16, 2006; Danish Patent Application No. PA 2006 01223 ...

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15-06-2017 дата публикации

Process for the Preparation of Substituted Oxiranes and Triazoles

Номер: US20170166540A1
Принадлежит: BASF AGRO B.V.

The present invention relates to a process for the preparation of oxirane compounds of formula II from keto compounds III using dimethyl sulfide (CH)S and dimethylsulfate (CH)SO, forming the reagent IV, trimethylsulfonium methylsulfate [(CH)SCHSO], in aqueous solution in the presence of potassium hydroxide (KOH). 111-. (canceled)13. The process of claim 12 , wherein essentially no organic solvent is added.14. The process of claim 12 , wherein the formation of the reagent of formula IV and the reaction of IV with compound III are carried out as a one-pot reaction.15. The process of claim 12 , wherein at least 2 equivalents of base per 1 equivalent of compound III are used.17. The process of claim 16 , wherein an inorganic base is used and less than 1 equivalent of said inorganic base is used per 1 equivalent of compound II.18. The process of claim 16 , wherein the product resulting from step (ii) is crystallized from toluene and/or ortho-xylene and/or an aliphatic alcohol and/or carbonic acid ester.19. The process of claim 18 , wherein the aliphatic alcohol is selected from the group consisting of methanol claim 18 , ethanol claim 18 , n-propanol claim 18 , iso-propanol claim 18 , n-butanol claim 18 , isobutanol and mixtures thereof.20. The process of claim 18 , wherein n-butyl acetate or ethyl acetate or a mixture thereof is used for crystallization.22. The process of claim 21 , wherein n-butyl acetate or ethyl acetate or a mixture thereof is used for crystallization. The present invention relates to a process for providing oxiranes comprising reacting a respective ketone with dimethylsulfate (CH)SOand dimethyl sulfide (CH)S in aqueous solution in the presence of potassium hydroxide (KOH), wherein dimethyl sulfide and dimethyl sulfate are used in a molar ratio of 1:1 to 2:1, and wherein apart from the reagents used at most 10 weight-% organic solvent in relation to the amount of compound III are added. Further, the present invention relates to a process for ...

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11-09-2014 дата публикации

PLEUROMUTILIN DERIVATIVES FOR THE TREATMENT OF DISEASES MEDIATED BY MICROBES

Номер: US20140256731A1
Принадлежит: NABRIVA THERAPEUTICS AG

Pleuromutilin derivative compounds of the following formula, and uses thereof for the treatment of diseases mediated by microbes, are disclosed:

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11-09-2014 дата публикации

1-[2-(2,4-Dimethylphenylsulfanyl)-Phenyl]Piperazine As A Compound With Combined Serotonin Reuptake, 5-HT3 And 5-HT1a Activity For The Treatment Of Cognitive Impairment

Номер: US20140256943A1
Принадлежит: H. Lundbeck A/S

1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine exhibits potent activity on SERT, 5-HTand 5-HTand may as such be useful for the treatment of cognitive impairment, especially in depressed patients.

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23-06-2016 дата публикации

N-heterocyclic carbene type palladium catalyst and its preparation method as well as applications

Номер: US20160175828A1

The present invention relates to an n-heterocyclic carbene (NHC) type palladium catalyst and its preparation method as well as applications. Its preparation process is as below: select glyoxal as the raw material to synthesize glyoxaldiimine in the presence of Lewis acid or Bronsted acid, and then react with paraformaldehyde to get the NHC type ligand. Use palladium (II) to react with the compound containing carbon-nitrogen double bonds to get palladium (II) cyclic dimer; make the palladium cyclic dimer and the NHC type ligand coordinated to get the NHC type palladium catalyst. The palladium catalyst with a brand new structure according to the present invention, boasts high activity and multi-purpose. In addition, it shows excellent reaction activity in a lot of catalytic-coupling reactions including Suzuki-Miyaura, Heck, Buchwald-Hartwig, Kumada-Tamao-Corriu, Sonogashira, Negishi and α-ketone arylation reactions, and some reactions even can be carried out with the presence of an extremely low concentration of catalyst, exhibiting favorable industrialization prospect.

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21-06-2018 дата публикации

BENZENESULFONAMIDE DERIVATIVES AS INVERSE AGONISTS OF RETINOID-RELATED ORPHAN RECEPTOR GAMMA (ROR GAMMA (T))

Номер: US20180170869A1
Принадлежит:

Benzenesulfonamide derivatives of formula (I), the pharmaceutically acceptable addition salts thereof, the hydrates and/or solvates thereof, and the use of same as inverse agonist of retinoid-related orphan receptor gamma (RORγt) are described. A pharmaceutical composition including such compounds, as well as the use thereof for the topical and/or oral treatment of RORγt receptor-medicated inflammatory diseases, in particular acne, psoriasis and/or atopic dermatitis are also described. 3. Compound as claimed in or , characterized in that L represents a single bond.10. Compound as claimed in any one of the preceding claims , as a medicament.11. Compound as claimed in any one of the preceding claims , for its use in the treatment of inflammatory disorders and/or autoimmune diseases mediated by the RORγt receptor.12. Compound as claimed in claim 10 , for its use in the treatment of acne.13. Compound as claimed in claim 10 , for its use in the treatment of psoriasis.14. Pharmaceutical composition comprising one or more compounds as defined in any one of to .15. Pharmaceutical composition as claimed in claim 14 , characterized for its use for treating inflammatory disorders and/or autoimmune diseases mediated by the RORγt receptor claim 14 , especially acne claim 14 , atopic dermatitis and/or psoriasis. The present invention relates to particular sulfonamide derivatives, to the pharmaceutically acceptable addition salts thereof, hydrates thereof and/or solvates thereof, and also to the use thereof as inverse agonist of the retinoid-related orphan receptor gamma RORγt.The invention also relates to a pharmaceutical composition comprising such compounds and also to the use thereof for the topical and/or oral treatment of inflammatory diseases mediated by the RORγt receptors, especially acne, atopic dermatitis and/or psoriasis.The nuclear receptors form a large family (known as a superfamily) of transcription factors which correspond to proteins that are capable of being ...

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22-06-2017 дата публикации

COMPOUNDS THAT ARE S1P MODULATING AGENTS AND/OR ATX MODULATING AGENTS

Номер: US20170174710A1
Принадлежит:

Compounds of formula (I) can modulate the activity of one or more S1P receptors and/or the activity of autotaxin (ATX). 3. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein B is selected from the group consisting of 9-azabicyclo[3.3.1]nonanyl claim 2 , 8-azabicyclo[3.2.1]octanyl claim 2 , decahydroisoquinolinyl claim 2 , 2-azaspiro[3.3]heptanyl claim 2 , bicyclo[3.2.1]octanyl claim 2 , 5-azaspiro[2.3]hexanyl claim 2 , 3-cyclohexylazetidinyl claim 2 , bicyclo[2.2.1]heptanyl claim 2 , adamantyl claim 2 , 6-oxa-9-azaspiro[4.5]decanyl claim 2 , 3-azabicyclo[3.3.1]nonanyl claim 2 , 6-oxa-2-azaspiro[3.4]octanyl claim 2 , 4-(1H-imidazol-4-yl)piperidinyl claim 2 , octahydro-1H-pyrido[1 claim 2 ,2-a]pyrazinyl claim 2 , 2 claim 2 ,3-dihydro-1H-indenyl claim 2 , (1R claim 2 ,5S)-bicyclo[3.1.0]hexanyl claim 2 , 3-azabicyclo[3.1.1]heptanyl claim 2 , 1-(pyridin-4-yl)piperazinyl claim 2 , 1-(pyridin-2-yl)piperazinyl claim 2 , 1-(pyridin-3-yl)piperazinyl claim 2 , 2-oxa-6-azaspiro[3.3]heptanyl claim 2 , 4-(pyrimidin-2-yl)piperazin-1-yl claim 2 , 3-azabicyclo[3.3.1]nonanyl claim 2 , 4-(pyridin-2-yl)piperidin-1-yl claim 2 , 4-phenylpiperazin-1-yl claim 2 , 4-phenylpiperidin-1-yl claim 2 , 4-(pyrazin-2-yl)piperazin-1-yl claim 2 , 4-(pyridin-2-yl)-1 claim 2 ,4-diazepan-1-yl claim 2 , 4-(pyrimidin-2-yl)-1 claim 2 ,4-diazepan-1-yl claim 2 , 4-(pyrimidin-4-yl)piperazin-1-yl claim 2 , 2 claim 2 ,7-diazaspiro[3.5]nonanyl claim 2 , 3-phenylazetidinyl claim 2 , 2-oxa-7-azaspiro[3.5]nonanyl claim 2 , 3-azabicyclo[3.1.0]hexanyl claim 2 , 2 claim 2 ,8-diazaspiro[4.5]decanyl claim 2 , 3-oxa-9-azabicyclo[3.3.1]nonanyl claim 2 , 7-azabicyclo[2.2.1]heptanyl claim 2 , spiro[3.5]nonanyl claim 2 , and tricyclo[2.2.1.02 claim 2 ,6]heptanyl.4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein B is a bridged ring system.6. (canceled)9. The compound according to claim 8 , or a pharmaceutically acceptable ...

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06-06-2019 дата публикации

Vortioxetine pamoic acid salt and crystal form thereof

Номер: US20190169147A1
Принадлежит:

The present application provides a vortioxetine pamoic acid salt, which includes a crystal form, a solvate or an amorphous substance of the vortioxetine pamoic acid salt. The present application provides a preparation method and use of the vortioxetine pamoic acid salt and the crystal form thereof. The vortioxetine pamoic acid salt prepared in the present application prolongs the residence time of the vortioxetine in vivo, achieving a slow release of the vortioxetine in vivo, and is suitable for preparing a long-acting dosage form. 1. A compound , which is a vortioxetine pamoic acid salt , with a structural formula of (CHNS).CHO.nHO , wherein r is 1 or 2 , n=0˜10.2. The compound according to claim 1 , characterized in that n is 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , 5 or 6.3. The compound according to claim 1 , characterized in that the vortioxetine pamoic acid salt is a crystalline substance claim 1 , a solvate claim 1 , or an amorphous substance.4. The compound according to claim 3 , characterized in that crystal form of the vortioxetine pamoic acid salt is crystal form A claim 3 , and in an X ray powder diffraction pattern of the crystal form A claim 3 , there are peaks at positions where 2θ is 12.96±0.2 claim 3 , 13.56±0.2 claim 3 , 16.67±0.2 claim 3 , 17.26±0.2 and 18.28±0.2 degrees.5. The compound according to claim 4 , characterized in that in an X ray powder diffraction pattern of the crystal form A claim 4 , there are peaks at one or more of positions where 2θ is 14.77±0.2 claim 4 , 18.28±0.2 claim 4 , 18.77±0.2 claim 4 , 19.98±0.2 claim 4 , 22.08±0.2 claim 4 , and 23.03±0.2 degrees.6. The compound according to claim 4 , characterized in that in an X ray powder diffraction pattern of the crystal form A claim 4 , there are peaks at one or more of positions where 2θ is 11.71±0.2 claim 4 , 12.41±0.2 claim 4 , 14.77±0.2 claim 4 , 18.28±0.2 claim 4 , 18.77±0.2 claim 4 , 19.98±0.2 claim 4 , 21.02±0.2 claim 4 , 22.08±0.2 claim 4 , 23.03±0.2 ...

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28-05-2020 дата публикации

1-[2-(2,4-DIMETHYLPHENYLSULFANYL)-PHENYL]PIPERAZINE AS A COMPOUND WITH COMBINED SEROTONIN REUPTAKE, 5-HT3 AND 5-HT1A ACTIVITY FOR THE TREATMENT OF COGNITIVE IMPAIRMENT

Номер: US20200163959A1
Принадлежит:

1-[2-(2,4-dimethylphenylsulphanyl)phenyl]piperazine exhibits potent activity on SERT, 5-HTand 5-HTand may as such be useful for the treatment of cognitive impairment, especially in depressed patients. 1. A pharmaceutical composition , comprising:a HBr salt of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine;mannitol;microcrystalline cellulose;sodium starch glycolate; andmagnesium stearate.2. The composition of claim 1 , wherein the composition comprises:a HBr salt of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine in an amount of 2-30% by weight of the composition;mannitol in an amount of 25-45% by weight of the composition;microcrystalline cellulose in an amount of 22-27% by weight of the composition;sodium starch glycolate in an amount of 4-5% by weight of the composition; andmagnesium stearate in an amount of 0.25-5% by weight of the composition.3. The composition of claim 2 , wherein the magnesium stearate is in an amount of 0.25-2% by weight of the composition.4. The composition of claim 1 , wherein the composition comprises:a HBr salt of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine in an amount of 20-22% by weight of the composition;mannitol in an amount of 35-36% by weight of the composition;microcrystalline cellulose in an amount of 24-25% by weight of the composition;sodium starch glycolate in an amount of 3-4% by weight of the composition; andmagnesium stearate in an amount of 0.25-1% by weight of the composition.5. The composition of claim 1 , wherein the composition comprises:a HBr salt of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine in an amount of 12-13% by weight of the composition;mannitol in an amount of 36-37% by weight of the composition;microcrystalline cellulose in an amount of 24-25% by weight of the composition;sodium starch glycolate in an amount of 3-4% by weight of the composition; andmagnesium stearate in an amount of 0.25-1% by weight of the composition.6. The composition of claim 1 , wherein the composition comprises ...

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08-07-2021 дата публикации

AMINO ALCOHOL-BORON-BINOL COMPLEX AND METHOD FOR PREPARING OPTICALLY ACTIVE AMINO ALCOHOL DERIVATIVE BY USING SAME

Номер: US20210206719A1
Принадлежит: MOLECULES & MATERIALS CO., LTD.

Disclosed are an amino alcohol-boron-binol complex as an intermediate, including Complex 3-1-1 shown below, and a method for preparing an optically active amino alcohol by using the same, wherein a racemic amino alcohol is resolved in an enation selective manner using a boron compound and a (R)- or (S)-binol, whereby an amino alcohol derivative with high optical purity can be prepared at high yield. 2. The method of claim 1 , wherein the boron compound of the first step is selected from the group consisting of boric acid claim 1 , trimethyl borate claim 1 , triethyl borate claim 1 , triisopropyl borate claim 1 , tributyl borate claim 1 , and triphenyl borate.4. The method of claim 1 , wherein the solvent in the first step is selected from the group consisting of acetonitrile claim 1 , dichloromethane claim 1 , toluene claim 1 , and isopropanol.5. The method of claim 1 , wherein the boron compound and the (R)- or (S)-binol are added in an amount of 1 mole equivalent and 0.45-0.6 mole equivalents claim 1 , respectively claim 1 , based on 1 mole equivalent of the racemic compound represented by Chemical Formula 1 in the first step. This application claims priority to Korean Application No. 10-2020-0001522, filed on Jan. 6, 2020, the entire disclosure of which is incorporated herein by reference.The present disclosure relates to an amino alcohol-boron-binol complex as an intermediate and a method for preparing an optically active amino alcohol derivative by using the same.Typical among chemically synthesized medication materials are racemates in which enantiomers are mixed. However, only one of the enantiomers in many racemic medications may be pharmacologically active whereas the other may be inactive or may even cause a side effect. For example, thalidomide exists in two mirror-image forms. Of the racemic mixture, one enantiomer has sedative effects whereas the other isomer is teratogenic. For ethambutol, one enantiomer is used to treat tuberculosis whereas another ...

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13-06-2019 дата публикации

PLEUROMUTILIN DERIVATIVES FOR THE TREATMENT OF DISEASES MEDIATED BY MICROBES

Номер: US20190175603A1
Принадлежит:

Pleuromutilin derivative compounds of the following formula (I), and uses thereof for the treatment of diseases mediated by microbes, are disclosed: 7. A compound according to one of the to , selected from the group consisting of14-O-{[(1S, 2S, 4S)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin14-O-{[(1R, 2R, 5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin14-O-{[(1S, 2S, 5R)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin14-O-{[(1R, 2R, 4S)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4R) diastereomer thereof14-O-{[(1R, 2R, 5R)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin14-O-{[(1S, 2S, 5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin14-O-{[(1R, 2R, 3R)-3-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 3S) diastereomer thereof14-O-{[(1R, 2R, 4R)-4-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4S) diastereomer thereof14-O-{[(1R, 2R, 4R)-4-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4S) diastereomer thereof14-O-{[(1R, 2R, 5S)-5-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof14-O-{[(1R, 2R, 5S)-5-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5R) diastereomer thereof14-O-{[(1R, 2R, 4S)-4-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4R) diastereomer thereof14-O-{[(1R, 2R, 5R)-5-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 5S) diastereomer thereof14-O-{[(1R, 2R, 3R)-3-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 3S) diastereomer thereof14-O-{[(1R, 2R, 3R)-3-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 3S) diastereomer thereof14-O-{[(1R, 2R, 4S)-4-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S, 4R) diastereomer thereof14-O-{[(1R, 2R, 5S)-5-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl ...

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14-07-2016 дата публикации

VORTIOXETINE SALT AND CRYSTAL THEREOF, THEIR PREPARATION METHOD, PHARMACEUTICAL COMPOSITIONS AND USAGE

Номер: US20160200698A1
Принадлежит:

The present invention relates to the novel vortioxetine salts, solvates and crystalline forms thereof, specifically, vortioxetine hemihydrobromide and a crystalline form thereof, and isopropanol solvate of vortioxetine hydrobromide and a crystalline form thereof. Compared to the known vortioxetine hydrobromide, the vortioxetine salts, solvates and crystalline forms of the present invention have improved features in stability, hygroscopicity and purity. The present invention also relates to preparation methods of the vortioxetine salts, solvates and crystalline forms, pharmaceutical compositions thereof and their uses in the manufacture of antidepressant drugs. 2. A preparation method of the vortioxetine hemihydrobromide according to claim 1 , which comprises the following procedures: respectively preparing solutions of vortioxetine and hydrobromic acid in solvents claim 1 , wherein the molar ratio of vortioxetine to hydrobromic acid is 10:1-2:1; mixing the two solutions to produce a suspension and stirring claim 1 , then removing the solvents by rotary evaporation to obtain the vortioxetine hemihydrobromide; wherein the solvents are selected from the group consisting of alcohols claim 1 , esters claim 1 , ketones and mixtures thereof.3. A crystalline form of the vortioxetine hemihydrobromide according to claim 1 , which is characterized in that claim 1 , measured with Cu-Kα radiation claim 1 , the X-ray powder diffraction pattern of the crystalline form of vortioxetine hemihydrobromide claim 1 , expressed as 2θ angles claim 1 , has the following characteristic peaks: 4.3±0.2° claim 1 , 14.9±0.2° claim 1 , 17.8±0.2° claim 1 , 18.9±0.2° claim 1 , 19.4±0.2° and 22.8±0.2°.4. The crystalline form of vortioxetine hemihydrobromide according to claim 3 , which is characterized in that claim 3 , measured with Cu-Kα radiation claim 3 , the X-ray powder diffraction pattern of the crystalline form of vortioxetine hemihydrobromide claim 3 , expressed as 2θ angles claim 3 , has ...

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13-07-2017 дата публикации

DEUTERIUM SUBSTITUTED 1-[2-(2,4-DIMETHYL-PHENYLSULFANYL) -PHENYL]PIPERAZINE COMPOUND OR DERIVATIVES THEREOF, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF

Номер: US20170197927A1
Принадлежит:

The present disclosure provides a deuterium substituted 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine compound with a structure represented by formula (I) or a derivative thereof, a pharmaceutical composition containing the compound or the derivative thereof, and an application of the compound or the derivative thereof in preparing drugs. The compound can reduce oxidative metabolism thereof, increase the drug concentration in blood and the effective bioavailability, so as to lower the dosage and reduce the toxicity and other side effects. The deuterium 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine compound and its derivative thereof provided by the present disclosure can be used to treat related diseases such as affective disorders, depression and anxiety. 2. The compound or the derivative thereof according to claim 1 , wherein one or more of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Ris/are a deuterium atom/deuterium atom(s).3. The compound or the derivative thereof according to claim 1 , wherein one or more of R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Ris/are a deuterium atom/deuterium atom(s).4. The compound or the derivative thereof according to claim 1 , which is selected from 1-[2-(2-methyl-4-trideuteriomethyl-phenylsulfanyl) phenyl]piperazine claim 1 , 1-{2-[2 claim 1 ,4-bis(trideuteriomethyl) phenylsulfanyl] phenyl}piperazine claim 1 , 1-[2-(2-methyl-4-dideuteriomethyl-phenylsulfanyl) phenyl]piperazine claim 1 , 1-{2-[2 claim 1 ,4-bis(monodeuteriomethyl) phenylsulfanyl] phenyl}piperazine claim 1 , 1-[2-(2-monodeuteriomethyl-4-trideuteriomethyl-phenylsulfanyl) phenyl]piperazine claim 1 , 1-[2-(2-methyl-4-trideuteriomethyl-phenylsulfanyl) phenyl]octodeuteriopiperazine and 1-{2-[2 claim 1 ,4-bis(trideuteriomethyl) phenylsulfanyl] phenyl}octodeuteriopiperazine.5. The compound or the derivative thereof according to claim 1 , wherein the pharmaceutically acceptable salt is an addition salt of the compound ...

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13-07-2017 дата публикации

COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE

Номер: US20170197977A9
Принадлежит: Cognition Therapeutics, Inc.

This invention relates to novel diarylamino compounds that bind to the sigma-2 receptor, to pharmaceutical compositions comprising such compounds, and to methods for inhibiting or restoring synapse loss in neuronal cells, modulating a membrane trafficking change in neuronal cells, and treating cognitive decline and neurodegenerative diseases and disorders therewith. 7. The compound of claim 6 , wherein{'sub': 1', '3, 'R=Cl, F, CF, or OH;'}{'sub': 2', '3', '1', '2, 'R=H, Cl, F, CF, or Rand Rare linked together to form a —O-ethylene-O-group;'}{'sub': 3', '3, 'R=CF; and'}{'sub': '4', 'R=methyl, and pharmaceutically acceptable salts thereof.'}17. A method/use for inhibiting an amyloid beta effect on a neuronal cell comprising administering an effective amount of a composition comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'A compound of in an amount effective to inhibit amyloid beta oligomer binding in said cell; and'}a pharmaceutically acceptable carrier.18. The method/use of claim 17 , wherein the compound is administered in an amount also effective to inhibit membrane trafficking deficits in said cell claim 17 , said membrane trafficking effects being associated with exposure of said cell to soluble amyloid beta oligomers.19. The method claim 17 , wherein the compound is in an amount effective to inhibit both the oligomer binding and synapse loss associated with exposure of the cell to soluble amyloid beta oligomer in said cell.20. The method of claim 17 , wherein the compound is administered in an amount effective to inhibit a soluble amyloid beta oligomer-mediated cognitive effect.21. (canceled)22. (canceled)23. (canceled)24. (canceled)25. The method/use of for inhibiting amyloid beta oligomer-induced synaptic dysfunction of a neuronal cell; comprising contacting the cell with the composition comprising a sigma-2 receptor antagonist compound in an amount effective to inhibit amyloid beta oligomer binding in said cell claim 17 , said dysfunction being ...

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25-09-2014 дата публикации

1-(2-PHENOXYMETHYLPHENYL)PIPERAZINE COMPOUNDS

Номер: US20140288089A1
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

The invention relates to compounds of formula I: 16-. (canceled)7. The method of claim 15 , where a is 0.814-. (canceled)16. The method of claim 15 , wherein the disorder or disease is a pain disorder selected from neuropathic pain claim 15 , fibromyalgia claim 15 , chronic low back pain claim 15 , and osteoarthritis. This application claims the benefit of U.S. Provisional Application No. 61/293,949, filed on Jan. 11, 2010; the entire disclosure of which is incorporated herein by reference.1. Field of the InventionThe present invention relates to 1-(2-phenoxymethylphenyl)piperazine compounds having activity as serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat a pain disorder, such as neuropathic pain, and other ailments.2. State of the ArtPain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (International Association for the Study of Pain (IASP), Pain Terminology). Chronic pain persists beyond acute pain or beyond the expected time for an injury to heal (American Pain Society. “Pain Control in the Primary Care Setting.” 2006:15). Neuropathic pain is pain initiated or caused by a primary lesion or dysfunction in the nervous system. Peripheral neuropathic pain occurs when the lesion or dysfunction affects the peripheral nervous system and central neuropathic pain when the lesion or dysfunction affects the central nervous system (IASP).Several types of therapeutic agents are currently used to treat neuropathic pain including, for example, tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs), calcium channel ligands (e.g., gabapentin and pregabalin), topical lidocaine, and opioid agonists (e.g., morphine, oxycodone, methadone, levorphanol and ...

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30-07-2015 дата публикации

ATX MODULATING AGENTS

Номер: US20150210647A1
Принадлежит:

Disclosed are bicyclic aryl compounds of formula (I), that can modulate the activity of the autotaxin (ATX) enzyme. This invention further relates to compounds that are ATX inhibitors, and methods of making and using such compounds in the treatment of demyelination due to injury or disease, as well as for treating proliferative disorders such as cancer. 3. The compound of claim 1 , wherein Aand Aare each independently CR.4. The compound of claim 1 , wherein Aand Aare each independently CR claim 1 , and one of A claim 1 , A claim 1 , and Ais N.5. The compound of claim 1 , wherein Aand Aare each independently CR claim 1 , and one of A claim 1 , A claim 1 , and Ais N claim 1 , and the others of A claim 1 , A claim 1 , and Aare each independently CR.9. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein:m is 1; and{'sup': 5', '11, 'Ris cyclobutyl, cyclopentyl, or cyclohexyl, each of which may be optionally substituted with from 1 to 3 independently selected R.'}10. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein Ris —COOH.11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein n is 1.12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof claim 11 , wherein Ris hydrogen claim 11 , and Ris Calkyl; or n is 1 claim 11 , and Rand Rtogether with the carbon to which they are attached are —C(═O)—.13. The compound of claim 11 , or a pharmaceutically acceptable salt thereof claim 11 , wherein Rand Rare each independently hydrogen.14. The compound of claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein Ris trifluoromethyl.15. The compound of claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , wherein q is 1 and Ris Calkyl.16. The compound of claim 14 , or a pharmaceutically acceptable salt thereof claim 14 , wherein q is 1 and Ris trifluoromethyl claim 14 , difluoromethyl or monofluoromethyl.17. The ...

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27-06-2019 дата публикации

Polymorphic Forms Of Vortioxetine Hydrobromide Tert-Butanolate

Номер: US20190194154A1
Принадлежит: Amneal Pharmaceuticals Co GmbH

The present invention provides novel polymorphic forms of vortioxetine hydrobromide (I).

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20-07-2017 дата публикации

METHOD OF PREPARING VORTIOXETINE

Номер: US20170204074A1
Принадлежит:

The new method of preparing 1-(2-(2,4-di-methylphenylsulphanyl)pheny!)piperazine of formula (I) or its salt comprises a reaction of 2-(2,4-dimethylphenyl-sulphanyl)benzeneamine of formula (XI), wherein Me is methyl, with a suitable precursor of formation of piperazine ring of formula (X11), wherein LG is a leaving group and R is hydrogen or a protective group, in a suitable organic solvent, wherein the reaction is carried out without presence of a base in a neutral or acidic environment. 2. The method according to claim 1 , wherein the reaction is carried out without presence of a base in a neutral or acidic environment.3. The method according to claim 1 , wherein the leaving group LG is selected from the group consisting of Cl claim 1 , Br claim 1 , I claim 1 , methylsulfonyloxy claim 1 , toluenesulfonyloxy claim 1 , and the protective group is COOR′ claim 1 , wherein R′ is an unbranched or branched C1-C5 alkyl group.5. The method according to claim 1 , wherein the organic solvent is an aromatic solvent selected from the group consisting of chlorobenzene claim 1 , xylene claim 1 , toluene claim 1 , α claim 1 ,α claim 1 ,α-trifluorotoluene and their mixtures.6. The method according to claim 1 , comprising reacting 2-(2 claim 1 ,4-dimethylphenylsulphanyl)benzeneamine of formula XI with 1-1.2 equivalents of bis-(2-chloroethyl)amine hydrochloride of formula XIIaa in toluene at a temperature of 103-111° C.8. The method according to claim 7 , wherein the reduction of the nitro compound of formula X is carried out with metals selected from the group consisting of Fe claim 7 , Zn claim 7 , and Sn claim 7 , with metal salts claim 7 , or by catalytic hydrogenation or transfer-hydrogenation in the presence of a catalyst based on Pt claim 7 , Pd claim 7 , Ni claim 7 , Fe claim 7 , or Co in a suitable solvent selected from C1-C5 alcohols and esters.9. The method according to claim 8 , wherein the reduction of the nitro compound of formula X is carried out by hydrogenation on ...

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28-07-2016 дата публикации

AN AMORPHOUS VORTIOXETINE AND SALTS THEREOF

Номер: US20160214949A1
Принадлежит:

The present invention relates to an amorphous vortioxetine and salts thereof. In particular, the invention relates to a process for the preparation of an amorphous vortioxetine hydrobromide. Further, the invention also relates to a process for preparation of amorphous vortioxetine free base. The invention also relates to pharmaceutical compositions comprising an amorphous vortioxetine or hydrobromide salt thereof for oral administration for treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). 2. A stable amorphous vortioxetine hydrobromide that does not convert to any other solid form and contains less than 0.5% (wt/wt) total impurities when stored at a temperature of up to about 40° C. and at a relative humidity of about 25% to about 75% for about three months or more.3. The amorphous vortioxetine hydrobromide according to having a purity by HPLC of greater than 98% and residual solvent less than 0.5%.4. A process for the preparation of amorphous vortioxetine hydrobromide claim 1 , the process comprising:(a) providing a solution of vortioxetine hydrobromide in one or more of solvents; and(b) obtaining the amorphous vortioxetine hydrobromide by the removal of the solvent.5. The process according to claim 4 , wherein the solvent comprises one or more of water claim 4 , alcohols claim 4 , ketones claim 4 , esters claim 4 , halogenated hydrocarbons claim 4 , acetonitrile claim 4 , dioxane claim 4 , dimethylsulfoxide claim 4 , or mixtures thereof.6. The process according to claim 5 , wherein the alcohol is selected from methanol claim 5 , ethanol claim 5 , isopropanol claim 5 , 2-propanol claim 5 , 1-butanol claim 5 , t-butyl alcohol claim 5 , 1-pentanol claim 5 , 2-pentanol claim 5 , amyl alcohol claim 5 , ethylene glycol claim 5 , and glycerol; the ketone is selected from acetone claim 5 , butanone claim 5 , 2-pentanone claim 5 , 3-pentanone claim 5 , methylbutyl ketone claim 5 , and methyl isobutyl ketone; the ester is selected from ...

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28-07-2016 дата публикации

VORTIOXETINE SALT AND CRYSTAL THEREOF, THEIR PREPARATION METHOD, PHARMACEUTICAL COMPOSITIONS AND USAGE

Номер: US20160214950A1
Принадлежит:

The present invention relates to the novel vortioxetine salts, solvates and crystalline forms thereof, specifically, vortioxetine hemihydrobromide and a crystalline form thereof, and isopropanol solvate of vortioxetine hydrobromide and a crystalline form thereof. Compared to the known vortioxetine hydrobromide, the vortioxetine salts, solvates and crystalline forms of the present invention have improved features in stability, hygroscopicity and purity. The present invention also relates to preparation methods of the vortioxetine salts, solvates and crystalline forms, pharmaceutical compositions thereof and their uses in the manufacture of antidepressant drugs. 2. A preparation method of the vortioxetine hemihydrobromide according to claim 1 , which comprises the following procedures: respectively preparing solutions of vortioxetine and hydrobromic acid in solvents claim 1 , wherein the molar ratio of vortioxetine to hydrobromic acid is 10:1-2:1; mixing the two solutions to produce a suspension and stirring claim 1 , then removing the solvents by rotary evaporation to obtain the vortioxetine hemihydrobromide; wherein the solvents are selected from the group consisting of alcohols claim 1 , esters claim 1 , ketones and mixtures thereof.3. The vortioxetine hemihydrobromide according to in a crystalline form claim 1 , which is characterized in that claim 1 , measured with Cu-Kα radiation claim 1 , the X-ray powder diffraction pattern of the crystalline form of vortioxetine hemihydrobromide claim 1 , expressed as 2θ angles claim 1 , has the following characteristic peaks: 4.3±0.2° claim 1 , 14.9±0.2° claim 1 , 17.8±0.2° claim 1 , 18.9±0.2° claim 1 , 19.4±0.2° and 22.8±0.2°.4. The vortioxetine hemihydrobromide according to claim 3 , which is characterized in that claim 3 , measured with Cu-Kα radiation claim 3 , the X-ray powder diffraction pattern of the crystalline form of vortioxetine hemihydrobromide claim 3 , expressed as 2θ angles claim 3 , has the following ...

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25-06-2020 дата публикации

SPHINGOSINE KINASE TYPE 1 INHIBITORS AND USES THEREOF

Номер: US20200197328A1
Принадлежит:

Provided are inhibitors of sphingosine kinase Type I that are useful in a number of applications, indications and diseases, as well as for monitoring pharmacokinetics and patient management. These compounds are applicable to treating ischemic diseases such as myocardial infarction and stroke. 5. The method of claim 4 , wherein R is a straight carbon chain claim 4 , a branched carbon chain claim 4 , a straight carbon chain comprising one or more heteroatoms claim 4 , a branched carbon chain comprising one or more heteroatoms claim 4 , a cyclic ring claim 4 , a heterocyclic ring claim 4 , an aromatic ring claim 4 , a hetero-aromatic ring claim 4 , or any combination of the foregoing.6. The method of claim 5 , wherein R is a straight carbon chain claim 5 , a branched carbon chain claim 5 , a straight carbon chain comprising one or more heteroatoms claim 5 , a branched carbon chain comprising one or more heteroatoms claim 5 , a cyclic ring claim 5 , a heterocyclic ring claim 5 , an aromatic ring claim 5 , or a hetero-aromatic ring.7. The method of claim 6 , wherein R is a straight carbon chain claim 6 , a branched carbon chain claim 6 , a straight carbon chain comprising one or more heteroatoms claim 6 , or a branched carbon chain comprising one or more heteroatoms.8. The method of claim 7 , wherein R is a straight carbon chain or a branched carbon chain.9. The method of claim 8 , wherein R is a straight carbon chain.15. The method of claim 14 , wherein R is a straight carbon chain claim 14 , a branched carbon chain claim 14 , a straight carbon chain comprising one or more heteroatoms claim 14 , a branched carbon chain comprising one or more heteroatoms claim 14 , a cyclic ring claim 14 , a heterocyclic ring claim 14 , an aromatic ring claim 14 , a hetero-aromatic ring claim 14 , or any combination of the foregoing.16. The method of claim 15 , wherein R is a straight carbon chain claim 15 , a branched carbon chain claim 15 , a straight carbon chain comprising one or ...

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26-07-2018 дата публикации

OXALIC ACID MONOAMIDE LIGAND, AND USES THEREOF IN COUPLING REACTION OF COPPER-CATALYZED ARYL HALOGEN SUBSTITUTE

Номер: US20180207628A1

The present invention provides oxalic amide ligands and uses thereof in copper-catalyzed coupling reaction of aryl halides. Specifically, the present invention provides a use of a compound represented by formula I, wherein definitions of each group are described in the specification. The compound represented by formula I can be used as a ligand in copper-catalyzed coupling reaction of aryl halides for the formation of C—N, C—O and C—S bonds. 3. The use of claim 1 , characterized in that R is selected from the group consisting of substituted or unsubstituted phenyl claim 1 , substituted or unsubstituted naphthyl claim 1 , substituted or unsubstituted benzyl claim 1 , C1-C4alkyl claim 1 , pyridyl claim 1 , and adamantyl;{'sub': 'a', 'Ris selected from (a) or (b)(a) OR′; wherein R′ is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl; or{'sub': '2', '(b) N(R″); wherein each R″ is independently selected from the group consisting of H, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure.'}5. The method of wherein claim 4 , in the reaction claim 4 , the molar ratio of the ligand to the reactant of aryl halide is 1-50:100 claim 4 , and preferably 5-20:100; and/orthe molar ratio of the ligand to the copper catalyst is 1-5: 1, and preferably 1-2:1.7. The method of wherein the reaction temperature is 50-180° C. claim 4 , and preferably 100-130° C. The present invention relates to the field of organic synthesis. Specifically, the present invention ...

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05-08-2021 дата публикации

CYCLOPROPANATION METHOD

Номер: US20210238133A1
Автор: KHASKIN EUGENE
Принадлежит:

A cyclopropanation method includes reacting an alcohol, an ester, or an aldehyde with a sulfone in an organic solvent containing a base providing a counter cation to form a cyclopropane; and isolating the cyclopropane. When using the alcohol or ester, the organic solvent further contains a catalyst having an alcohol dehydrogenation activity. 1. A cyclopropanation method , comprising:reacting an alcohol, an ester, or an aldehyde with a sulfone in an organic solvent containing a base providing a counter cation to form a cyclopropane; and,isolating the cyclopropane;wherein, the organic solvent further contains a catalyst having an alcohol dehydrogenation activity when the alcohol or the ester is reacted.2. The cyclopropanation method according to ;wherein, the alcohol is reacted;{'sup': 1', '1, 'sub': '2', 'the alcohol is RCHOH, in which Ris hydrogen, alkyl, or cycloalkyl, and the alkyl is optionally intervened by oxygen, sulfur, or nitrogen;'}{'sup': '1', 'Ris saturated or unsaturated, provided that a double bond does not exist between a β carbon and a γ carbon of the alcohol;'}{'sup': '1', 'Ris unsubstituted or substituted with at least one substituent selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, provided that the β carbon of the alcohol is unsubstituted; and,'}the substituent is further substituted or unsubstituted.4. The cyclopropanation method according to claim 1 ,wherein, the ester is reacted,{'sup': 1', '2, 'sub': '2', 'the ester is formed from RCHOH and RCOOH;'}{'sup': '1', 'Ris hydrogen, alkyl, or cycloalkyl, and the alkyl is optionally intervened by oxygen, sulfur, or nitrogen,'}{'sup': '1', 'Ris saturated or unsaturated, provided that a double bond does not exist between a β carbon and a γ carbon of the alcohol,'}{'sup': '1', 'Ris unsubstituted or substituted with at least one substituent selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, provided that the β ...

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04-08-2016 дата публикации

NEW SULFONYLAMINOBENZAMIDE COMPOUNDS

Номер: US20160221937A1
Принадлежит:

The present invention relates to a new compound of formula (I) wherein the variables have the meaning as indicated in the claims; or an enantiomer or salt thereof. The compounds of formula (I) are useful in the control of parasites, in particular endoparasites, in and on vertebrates. 2. A compound of formula (I) according to claim 1 , wherein each R is independently halogen; C-C-alkyl; C-C-haloalkyl; amino; C-C-alkoxy; C-C-haloalkoxy; C-C-haloalkylthio; C-C-alkylsulfonyl; C-C-haloalkylsulfonyl; tri-C-C-alkylsilyl; C-C-alkoxycarbonyl; N-mono- or N claim 1 ,N-di-C-C-alkylaminocarbonyl; aminosulfonyl; N-mono- or N claim 1 ,N-di-C-C-alkylaminosulfonyl; N—C-C-alkyl-N—C-C-alkoxycarbonylamino; cyano; nitro; or 5- or 6-membered heterocycloalkyl comprising 1 or 2 same or different heteroatoms selected from O claim 1 , S and N claim 1 , which is unsubstituted or substituted by halogen claim 1 , C-C-alkyl claim 1 , C-C-haloalkyl or C-C-alkoxy.3. A compound of formula (I) according to claim 1 , wherein each R is halogen claim 1 , C-C-alkyl claim 1 , C-C-haloalkyl claim 1 , C-C-alkoxy claim 1 , C-C-haloalkoxy or cyano claim 1 , in particular chlorine claim 1 , fluorine or CF.4. A compound of formula (I) according to claim 3 , wherein m is an integer 1 claim 3 , 2 or 3 claim 3 , preferably 1 or 2 claim 3 , and in particular 1.5. A compound of formula (I) according to claim 4 , wherein each Ris independently halogen; C-C-alkyl; C-C-haloalkyl; C-C-cycloalkyl; C-C-alkoxy; C-C-haloalkoxy; C-C-haloalkylthio; SF; N claim 4 ,N-di-C-C-alkylamino-C-C-alkylaminocarbonyl; N—C-C-alkylsulfonylamino; cyano; nitro; hydroxy; B(OH) claim 4 , morpholino; or phenyl claim 4 , benzoyl claim 4 , pyridyloxy claim 4 , pyrimidinyloxy or benzothiazloyl claim 4 , which is each unsubstituted or substituted by halogen claim 4 , C-C-alkyl claim 4 , C-C-haloalkyl claim 4 , C-C-cycloalkyl or C-C-alkoxy.6. A compound of formula (I) according to claim 4 , wherein each Ris independently halogen; C-C-alkyl; C-C- ...

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11-07-2019 дата публикации

Vortioxetine Pyroglutamate

Номер: US20190210987A1
Принадлежит:

The present invention provides vortioxetine pyroglutamate salt and pharmaceutical compositions comprising said salt 1. Vortioxetine pyroglutamate.2. The compound according to claim 1 , wherein the compound is selected from the group consisting of vortioxetine (L)-pyroglutamate claim 1 , vortioxetine (D)-pyroglutamate and vortioxetine (DL)-pyroglutamate.3. The compound according to claim 1 , wherein the compound is vortioxetine (L)-pyroglutamate or vortioxetine (D)-pyroglutamate in crystalline form with XRPD reflections at 10.72 claim 1 , 12.14 claim 1 , 16.22 and 18.59 (°2θ) (±0.1°2θ).4. The compound according to claim 1 , wherein the compound is vortioxetine (DL)-pyroglutamate monohydrate in crystalline form with XRPD reflections at 6.16 claim 1 , 9.25 claim 1 , 17.68 and 18.12 (°2θ) (±0.1°2θ).5. The compound according to claim 1 , wherein the compound is vortioxetine (DL)-pyroglutamate α-form in crystalline form with XRPD reflections at 14.27 claim 1 , 15.75 claim 1 , 17.06 and 18.59 (°2θ) (±0.1°2θ).6. A pharmaceutical composition claim 1 , comprising the compound of together with at least one pharmaceutically acceptable carrier or diluent.7. A gelable pharmaceutical composition claim 1 , comprising the compound of and a salt.8. A gel claim 1 , comprising the compound of claim 1 , a salt and water.9. A solid pharmaceutical composition for oral administration claim 1 , comprising the compound of and an enteric coating.10. A method for preparing a gel claim 1 , said method comprising mixing the compound of claim 1 , a salt and an aqueous solution.11. A method for the treatment of a disease selected from major depressive disorder; major depressive episode; general anxiety disorder; obsessive compulsive disorder (OCD) claim 1 , panic disorder; post traumatic stress disorder; cognitive impairment; mild cognitive impairment (MCI); cognitive impairment associated with Alzheimer's disease claim 1 , depression claim 1 , schizophrenia (CIAS); and attention deficit ...

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10-08-2017 дата публикации

1,4-Disubstituted Piperidines, 1,4-Disubstituted Piperazines, 1,4-Disubstituted Diazepines, and 1,3-Disubstituted Pyrrolidine Compounds

Номер: US20170226072A1

The present invention is directed to 1,4-disubstituted piperidines, 1,4-disubstituted piperazines, 1,4-disubstituted diazepanes, and 1,3-disubstituted pyrrolidine compounds and their use.

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16-08-2018 дата публикации

PROCESS FOR THE PREPARATION OF VORTIOXETINE AND SALTS THEREOF

Номер: US20180230116A1
Принадлежит: Piramal Enterprises Limited

The present invention provides an improved process for preparation of 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine; commonly known as vortioxetine (referred to as the compound (I)) and pharmaceutically acceptable salts thereof; wherein the process comprises reaction of 2-((2,4-dimethylphenyl)thio)aniline (II) with bis(2-alkyl)amine (IIIa) or its salt in the presence of a cyclic amide solvent. 2. The process according to the claim 1 , wherein the cyclic amide solvent is selected from the group consisting of N-methyl-2-pyrrolidone (NMP) claim 1 , caprolactam claim 1 , 2-piperidinone claim 1 , azetidin-2-one claim 1 , N-methyl caprolactame claim 1 , 1-methylpiperidin-2-one and/or 1-methylazetidin-2-one; or a mixture thereof.3. The process according to the claim 1 , wherein the reaction is performed at temperature ranging between 80-180° C.4. The process according to the claim 1 , wherein the product vortioxetine (I) or its salt is obtained in a yield of about 70%.5. The process according to the claim 1 , wherein the product vortioxetine (I) or its salt is obtained with in a purity of at least 99% (HPLC).6. The process according to the claim 1 , wherein the obtained product vortioxetine (I) or its salt is further transformed into another acid addition salt of vortioxetine.8. A compound Vortioxetine (I) hydrobromide having particle size diameter with d (10) of about less than 12 μm or d (50) of about less than 40 μm or d (90) of about less than 180 μm; or any combination thereof.9. The compound according to the claim 8 , wherein the compound Vortioxetine (I) hydrobromide having particle size distribution range of d(10) between about 5 to about 12 μm claim 8 , d(50) between about 30 to about 40 μm or d(90) between about 80 to about 180 μm; or any combination thereof.10. A compound Vortioxetine (I) hydrobromide having specific surface area value from 0.05 to 2 m/g. The present invention relates to an improved process for the preparation of 1-[2-(2,4-dimethyl- ...

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23-08-2018 дата публикации

SPHINGOSINE KINASE TYPE 1 INHIBITORS AND USES THEREOF

Номер: US20180235907A1
Принадлежит:

Provided are inhibitors of sphingosine kinase Type I that are useful in a number of applications, indications and diseases, as well as for monitoring pharmacokinetics and patient management. These compounds are applicable to treating tumors of the central nervous system, such as glioblastoma multiforme (GBM). 5. The method of claim 4 , wherein R is a straight carbon chain claim 4 , a branched carbon chain claim 4 , a straight carbon chain comprising one or more heteroatoms claim 4 , a branched carbon chain comprising one or more heteroatoms claim 4 , a cyclic ring claim 4 , a heterocyclic ring claim 4 , an aromatic ring claim 4 , a hetero-aromatic ring claim 4 , or any combination of the foregoing.6. The method of claim 5 , wherein R is a straight carbon chain claim 5 , a branched carbon chain claim 5 , a straight carbon chain comprising one or more heteroatoms claim 5 , a branched carbon chain comprising one or more heteroatoms claim 5 , a cyclic ring claim 5 , a heterocyclic ring claim 5 , an aromatic ring claim 5 , or a hetero-aromatic ring.7. The method of claim 6 , wherein R is a straight carbon chain claim 6 , a branched carbon chain claim 6 , a straight carbon chain comprising one or more heteroatoms claim 6 , or a branched carbon chain comprising one or more heteroatoms.8. The method of claim 7 , wherein R is a straight carbon chain or a branched carbon chain.9. The method of claim 8 , wherein R is a straight carbon chain.14. The method of claim 13 , wherein R is a straight carbon chain claim 13 , a branched carbon chain claim 13 , a straight carbon chain comprising one or more heteroatoms claim 13 , a branched carbon chain comprising one or more heteroatoms claim 13 , a cyclic ring claim 13 , a heterocyclic ring claim 13 , an aromatic ring claim 13 , a hetero-aromatic ring claim 13 , or any combination of the foregoing.15. The method of claim 14 , wherein R is a straight carbon chain claim 14 , a branched carbon chain claim 14 , a straight carbon chain ...

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06-11-2014 дата публикации

PARACYCLOPHANE-BASED LIGANDS, THEIR PREPARATION AND USE IN CATALYSIS

Номер: US20140330012A1
Автор: Ruan Jiwu, Xiao Jianliang
Принадлежит: JOHNSON MATTHEY PUBLIC LIMITED COMPANY

A substituted paracyclophane of formula (I) is provided 2. The metal complex according to wherein the metal compound is a compound of palladium (Pd) claim 1 , platinum (Pt) claim 1 , rhodium (Rh) claim 1 , iridium (Ir) or ruthenium (Ru).3. The metal complex according to wherein the substituted paracyclophane (I) is substantially enantiomerically-pure.4. The metal complex according to wherein the metal complex is supported on a solid support.5. The metal complex according to wherein the substituted paracyclophane (I) is substantially enantiomerically-pure.6. A method of asymmetrically hydrogenating a substrate claim 2 , comprising performing the hydrogenation in the presence of a metal complex according to .7. A method of catalyzing a reaction claim 2 , comprising performing the reaction in the presence of a metal complex according to claim 2 , wherein the reaction is selected from the group consisting of carbon-carbon coupling reactions claim 2 , enantioselective isomerization of olefins claim 2 , asymmetric hydroboration reactions claim 2 , asymmetric cyclisation of olefinic aldehydes claim 2 , asymmetric arylation reactions claim 2 , asymmetric alkylation reactions and amination of aryl halides (Hartwig-Buchwald reaction). This application is a Division of U.S. patent application Ser. No.12/675,918, filed Oct. 22, 2010, which is the U.S. National Phase filing of PCT International Application No. PCT/GB2008/050730, filed Aug. 21, 2008, and claims priority of British Patent Application No. 0716714.1, filed Aug. 29, 2007, the disclosures of which applications are incorporated herein by reference in their entirety.This invention relates to ligands used in transition metal-catalysed reactions and in particular to substituted paracyclophanes.Paracyclophanes and in particular [2.2]-paracyclophane derivatives are established ligands for transition metal-catalysed asymmetric reactions (see for example, S. E. Gibson and J. D. Knight, 2003, 1, 1256-1269). Of these, ...

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23-07-2020 дата публикации

LIQUID CRYSTAL DEVICE, METHOD FOR PRODUCING SAME, AND COMPOUND

Номер: US20200231875A1
Автор: UESAKA YUUSUKE
Принадлежит: JSR Corporation

This liquid crystal display device is provided with: a pair of substrates which have conductive films, respectively; a liquid crystal layer which is arranged between the pair of substrates and contains a liquid crystal; and a liquid crystal control layer which is formed on the substrate-side interface of the liquid crystal layer by means of polymerization of a polymerizable monomer, and which controls the alignment of the liquid crystal. With respect to this liquid crystal display device, at least one of the pair of substrates is not provided with a liquid crystal alignment film, and the liquid crystal control layer contains a compound that has at least one partial structure which is selected from the group consisting of a fluorene structure-containing group, an aromatic amino group and a nitrogen-containing aromatic heterocyclic group. 1. A liquid crystal device , comprising:a pair of substrates each having a conductive film;a liquid crystal layer which is disposed between the pair of substrates and contains a liquid crystal; anda liquid crystal control layer which is formed at an interface on a side of the substrate of the liquid crystal layer through polymerization of polymerizable monomers and controls alignment of the liquid crystal,wherein no liquid crystal alignment film is formed on at least one of the pair of substrates, andwherein the liquid crystal control layer contains a compound [A] having at least one partial structure selected from the group consisting of a fluorene structure-containing group, an aromatic amino group and a nitrogen-containing aromatic heterocyclic group.3. The liquid crystal device according to claim 1 ,wherein the liquid crystal control layer contains at least one selected from the group consisting of a polymerization initiator, a photosensitizer and a polymerization inhibitor.5. The liquid crystal device according claim 1 ,wherein the liquid crystal has negative dielectric anisotropy.6. A method for producing a liquid crystal ...

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09-09-2021 дата публикации

Phenyl-Piperazine Derivatives As Serotonin Reuptake Inhibitors

Номер: US20210276966A1
Принадлежит:

The invention provides compounds represented by the general formula I 115-. (canceled)16. A pharmaceutical composition , comprising:1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine or a hydrobromic acid addition salt thereof, andat least one pharmaceutically acceptable carrier or diluent.17. The composition of claim 16 , wherein the composition comprises a hydrobromic acid addition salt of 1-[2-(2 claim 16 ,4-dimethylphenylsulfanyl)phenyl]piperazine.18. The composition of claim 17 , wherein the composition is a tablet.19. The composition of claim 18 , wherein the composition comprises 1-[2-(2 claim 18 ,4-dimethylphenylsulfanyl)phenyl]piperazine in an amount of from 0.01 mg to 100 mg.201. A method for the treatment of an affective disorder in a human in need thereof claim 18 , comprising administering to the human an amount of the composition of claim comprising a therapeutically effective amount of 1-[2-(2 claim 18 ,4-dimethylphenylsulfanyl)phenyl]piperazine or a hydrobromic acid addition salt thereof.21. The method of claim 20 , wherein the affective disorder is depression.22. The method of claim 20 , wherein the affective disorder is an anxiety disorder.23. The method of claim 22 , wherein the anxiety disorder is general anxiety disorder or panic disorder.24. The method of claim 20 , wherein the affective disorder is obsessive compulsive disorder.25. The method of claim 20 , wherein the composition comprises a therapeutically effective amount of a hydrobromic acid addition salt of 1-[2-(2 claim 20 ,4-dimethylphenylsulfanyl)phenyl]piperazine.26. The method of claim 25 , wherein the affective disorder is depression.27. The method of claim 25 , wherein the affective disorder is an anxiety disorder.28. The method of claim 27 , wherein the anxiety disorder is general anxiety disorder or panic disorder.29. The method of claim 25 , wherein the affective disorder is obsessive compulsive disorder.30. The method of claim 25 , wherein the composition is a tablet.31. The ...

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