PROCESS FOR THE PREPARATION OF A DIARYLTHIOHYDANTOIN COMPOUND

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

Process for the preparation of a diarylthiohydantoin compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

PROCESSES FOR THE PREPARATION OF A DIARYLTHIOHYDANTOIN COMPOUND

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer. 3. The process of wherein the amide coupling agent is 1 claim 2 ,1-carbonyldiimidazole and the catalyst is DBU.6. The process of claim 5 , comprising reacting compound (XIII) with a compound of formula (2c-1) in the presence of cuprous bromide; in the presence of TMEDA; in the presence of potassium acetate; in organic solvent DMA; at a temperature in the range of from about 80° C. to about 140° C.7. The process of claim 5 , comprising reacting compound (XIII) with a compound of formula (2c-1) in the presence of a copper (0) source that is copper powder or copper sponge; in the presence of potassium acetate or sodium pivalate; in organic solvent DMSO; at a temperature in the range of from about 0° C. to about 80° C.8. The process of claim 5 , comprising reacting compound (XIII) with a compound of formula (2c-1) in the presence of a copper (0) source that is copper powder or copper sponge; in the presence of potassium acetate; with the addition of a copper (I) salt selected from the group consisting of cuprous chloride claim 5 , cuprous iodide claim 5 , cuprous bromide claim 5 , and cuprous acetate; in organic solvent DMSO; at a temperature in the range of from about 0° C. to about 80° C.10. The process of claim 9 , wherein step (2e) further comprises reacting compound (XVII) with a thiocarbonyl source selected from the group consisting of O claim 9 ,O′-di(pyridin-2-yl)carbonothioate claim 9 , 1 claim 9 ,1′-thiocarbonylbis(pyridin-2(1H)-one) claim 9 , di(1H-imidazol-1-yl)methanethione claim 9 , thiophosgene claim 9 , phenyl thionochloroformate claim 9 , O-(2-naphthyl) thionochloroformate claim 9 , tolyl thionochloroformate claim 9 , and thiocarbonyl bis(benzotriazole); in the presence of an activating agent selected from the group consisting of DMAP claim 9 , NaH claim 9 , and NaOH; in an organic solvent selected ...

PROCESSES FOR THE PREPARATION OF A DIARYLTHIOHYDANTOIN COMPOUND

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

MONO-HYDROCHLORIC SALTS OF AN INHIBITOR OF HISTONE DEACETYLASE

This invention provides novel crystalline forms of mono-HCl salts and a mono-HCl salt hydrate of JNJ-26481585, an inhibitor of histone deacetylases. The invention also relates to processes for production of these forms, to intermediates used in these processes, to pharmaceutical compositions comprising these forms, and to the use of these forms in medical treatment for instance as a medicine to inhibit proliferative conditions, such as cancer and leukemia. 2. The mono-hydrochloric salt of wherein said salt is in crystalline Form I claim 1 , Form II or in a hydrate form.3. The mono-hydrochloric salt of or in crystalline Form I wherein said crystalline form has an X-ray powder diffraction pattern comprising peaks at 15.1°±0.2° claim 1 , 17.2°±0.2° claim 1 , 23.4°±0.2° claim 1 , 24.4°±0.2° and 27.7°±0.2°.4. The mono-hydrochloric salt of wherein the X-ray powder diffraction pattern further comprises peaks at 7.6°±0.2° claim 3 , 12.0°±0.2° and 12.5°±0.2°.5. The mono-hydrochloric salt of any of to wherein the crystalline form has an infrared spectrometry micro attenuated reflectance spectrum with peaks at 3119±1 cm claim 3 , 2756±1 cm claim 3 , 1634±1 cm claim 3 , 1475±1 cm claim 3 , 1371±1 cm claim 3 , 1333±1 cm claim 3 , 1275±1 cm claim 3 , 1226±1 cm claim 3 , 1128±1 cmand 1066 cm±1 cm.6. The mono-hydrochloric salt of any of to wherein the crystalline form has a differential scanning calorimetry curve with an endothermic peak at about 216.8° C.7. The mono-hydrochloric salt of any of to wherein the crystalline form adsorbs up to 0.6% water at high relative humidity.8. The mono-hydrochloric salt of or in hydrate form wherein said hydrate form has an X-ray powder diffraction pattern comprising peaks at 10.0°±0.2° claim 3 , 13.4°±0.2° and 26.5°±0.2°.9. The mono-hydrochloric salt of wherein the X-ray powder diffraction pattern further comprises peaks at 21.6°±0.2° and 24.9°±0.2°.10. The mono-hydrochloric salt of or wherein the crystalline form has an infrared spectrometry ...

PYRAZOLYL QUINAZOLINE KINASE INHIBITORS

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer. 3. A compound according to wherein each Ris hydrogen; a N-oxide thereof claim 1 , a pharmaceutically acceptable salt thereof or a solvate thereof.4. A compound according to wherein Rrepresents Calkyl; a N-oxide thereof claim 1 , a pharmaceutically acceptable salt thereof or a solvate thereof.5. A compound according to wherein Rrepresents CH— or CD-; a N-oxide thereof claim 1 , a pharmaceutically acceptable salt thereof or a solvate thereof.6. A compound according to wherein Ris independently selected from halogen claim 1 , cyano claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkoxy claim 1 , hydroxyCalkyl claim 1 , hydroxyCalkoxy claim 1 , haloCalkoxy claim 1 , CalkoxyCalkyl claim 1 , R claim 1 , Calkoxy substituted with R claim 1 , —C(═O)—R claim 1 , Calkyl substituted with NRR claim 1 , Calkoxy substituted with NRR claim 1 , —NRRand —C(═O)—NRR; a N-oxide thereof claim 1 , a pharmaceutically acceptable salt thereof or a solvate thereof.7. A compound according to wherein Rrepresents Calkyloxy; a N-oxide thereof claim 6 , a pharmaceutically acceptable salt thereof or a solvate thereof.8. A compound according to wherein Rrepresents CHO— or CDO—; a N-oxide thereof claim 6 , a pharmaceutically acceptable salt thereof or a solvate thereof.9. A compound according to wherein Rrepresents Calkyl claim 1 , hydroxyCalkyl claim 1 , hydroxyhaloCalkyl claim 1 , haloCalkyl claim 1 , Calkyl substituted with —C(═O)—Calkyl claim 1 , CalkoxyCalkyl wherein each Calkyl may optionally be substituted with one or two hydroxyl groups claim 1 , Calkyl substituted with R claim 1 , Calkyl substituted with —NRR claim 1 , Calkyl substituted with hydroxyl and —NRR claim 1 , Calkyl substituted with one or two halogens and —NRR claim 1 , Calkyl ...

PYRAZOLYL QUINOXALINE KINASE INHIBITORS

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

PYRAZOLYL QUINOXALINE KINASE INHIBITORS

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer. 2. A method according to claim 1 , wherein the compound is selected from the group consisting of a compound of formula (I) claim 1 , a tautomeric form claim 1 , stereochemically isomeric form and isotopic form thereof claim 1 , wherein{'sup': '1', 'Ris'}hydrogen,{'sub': '1-6', 'Calkyl,'}{'sub': '1-6', 'hydroxyCalkyl,'}{'sub': '1-6', 'haloCalkyl,'}{'sub': 1-6', '1-6', '1-6, 'CalkoxyCalkyl wherein each Calkyl is optionally substituted with one or two hydroxyl groups,'}{'sub': '1-6', 'sup': 4', '5, 'Calkyl substituted with —NRR,'}{'sub': '1-6', 'sup': 4', '5, 'Calkyl substituted with —C(═O)—NRR,'}{'sub': 2', '1-6, '—S(═O)—Calkyl,'}{'sub': '2', 'sup': 14', '15, '—S(═O)—NRR,'}{'sub': 1-6', '2', '1-6, 'Calkyl substituted with —S(═O)—Calkyl,'}{'sub': 1-6', '2', '1-6, 'Calkyl substituted with —NH—S(═O)—Calkyl,'}{'sup': '6', 'R,'}{'sub': '1-6', 'sup': '6', 'Calkyl substituted with R,'}{'sub': '1-6', 'sup': '6', 'Calkyl substituted with —C(═O)—R,'}{'sub': '1-6', 'sup': '6', 'hydroxyCalkyl substituted with R, or'}{'sub': 1-6', '3', '3, 'Calkyl substituted with —Si(CH);'}{'sup': '1a', 'each Ris hydrogen;'}{'sup': 10', '11, 'Rand Rare each independently'}hydrogen,{'sub': '1-6', 'Calkyl,'}{'sub': '1-6', 'cyanoCalkyl,'}{'sub': '1-6', 'sup': 14', '15, 'Calkyl substituted with —NRR,'}{'sub': '1-6', 'sup': 14', '15, 'Calkyl substituted with —C(═O)—NRR,'}{'sub': '1-6', 'haloCalkyl,'}{'sub': '1-6', 'hydroxyCalkyl,'}{'sub': '1-6', 'hydroxyhaloCalkyl,'}{'sub': '1-6', 'Calkoxy,'}{'sub': 1-6', '1-6', '1-6, 'CalkoxyCalkyl wherein each Calkyl is optionally substituted with one or two hydroxyl groups,'}{'sup': '6', 'R,'}{'sub': '1-6', 'sup': '6', 'Calkyl substituted with R,'}{'sup': '6', '—C(═O)—R,'}{'sub': '1-6', '—C(═O)—Calkyl,'}{'sub': '1-6', '—C ...

PYRAZOLYL QUINOXALINE KINASE INHIBITORS

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer. 15-. (canceled)7. A compound according to wherein{'sup': '1', 'claim-text': hydrogen,', {'sub': '1-6', 'Calkyl,'}, {'sub': '1-6', 'hydroxyCalkyl,'}, {'sub': '1-6', 'haloCalkyl,'}, {'sub': 1-6', '1-6', '1-6, 'CalkoxyCalkyl wherein each Calkyl is optionally substituted with one or'}, 'two hydroxyl groups,', {'sub': '1-6', 'sup': 4', '5, 'Calkyl substituted with —NRR,'}, {'sub': '1-6', 'sup': 4', '5, 'Calkyl substituted with —C(═O)—NRR,'}, {'sub': 2', '1-6, '—S(═O)—Calkyl,'}, {'sub': '2', 'sup': 14', '15, '—S(═O)—NRR,'}, {'sub': 1-6', '2', '1-6, 'Calkyl substituted with —S(═O)—Calkyl,'}, {'sub': 1-6', '2', '1-6, 'Calkyl substituted with —NH—S(═O)—Calkyl,'}, {'sup': '6', 'R,'}, {'sub': '1-6', 'sup': '6', 'Calkyl substituted with R,'}, {'sub': '1-6', 'sup': '6', 'Calkyl substituted with —C(═O)—R,'}, {'sub': '1-6', 'sup': '6', 'hydroxyCalkyl substituted with R, or'}, {'sub': 1-6', '3', '3, 'Calkyl substituted with —Si(CH);'}, {'sup': '1a', 'wherein each Ris hydrogen;'}], 'Ris'}or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof.8. A compound according to wherein each Ris hydrogen; or an N-oxide thereof claim 6 , a pharmaceutically acceptable salt thereof or a solvate thereof.9. A compound according to wherein Ris Calkyl; or an N-oxide thereof claim 6 , a pharmaceutically acceptable salt thereof or a solvate thereof.10. A compound according to wherein Ris CH— or CD-; or an N-oxide thereof claim 6 , a pharmaceutically acceptable salt thereof or a solvate thereof.11. A compound according wherein Ris independently selected from halogen claim 6 , cyano claim 6 , Calkyl claim 6 , Calkenyl claim 6 , Calkoxy claim 6 , hydroxyCalkyl claim 6 , hydroxyCalkoxy claim 6 , haloCalkoxy claim 6 , CalkoxyCalkyl ...

Processes for the preparation of a diarylthiohydantoin compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

PYRAZOLYL QUINOXALINE KINASE INHIBITORS

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer. 2. A compound according to wherein Rrepresents hydrogen claim 1 , Calkyl claim 1 , hydroxyCalkyl claim 1 , haloCalkyl claim 1 , CalkoxyCalkyl wherein each Calkyl may optionally be substituted with one or two hydroxyl groups claim 1 , Calkyl substituted with —NRR claim 1 , Calkyl substituted with —C(═O)—NRR claim 1 , —S(═O)—Calkyl claim 1 , —S(═O)—NRR claim 1 , Calkyl substituted with —S(═O)—Calkyl claim 1 , Calkyl substituted with —NH—S(═O)—Calkyl claim 1 , R claim 1 , Calkyl substituted with R claim 1 , Calkyl substituted with —C(═O)—R claim 1 , hydroxyCalkyl substituted with R claim 1 , or Calkyl substituted with —Si(CH); wherein each Ris hydrogen; wherein Rand Reach independently represent hydrogen claim 1 , Calkyl claim 1 , cyanoCalkyl claim 1 , Calkyl substituted with —NRR claim 1 , Calkyl substituted with —C(═O)—NRR claim 1 , haloCalkyl claim 1 , hydroxyCalkyl claim 1 , hydroxyhaloCalkyl claim 1 , Calkoxy claim 1 , CalkoxyCalkyl wherein each Calkyl may optionally be substituted with one or two hydroxyl groups claim 1 , R claim 1 , Calkyl substituted with R claim 1 , —C(═O)—R claim 1 , —C(═O)—Calkyl claim 1 , —C(═O)-hydroxyCalkyl claim 1 , —C(═O)-haloCalkyl claim 1 , —C(═O)-hydroxyhaloCalkyl claim 1 , Calkyl substituted with —Si(CH) claim 1 , —S(═O)—C-alkyl claim 1 , —S(═O)-haloCalkyl claim 1 , —S(═O)—NRR claim 1 , Calkyl substituted with —S(═O)—C claim 1 , Calkyl substituted with —S(═O)-haloCalkyl claim 1 , Calkyl substituted with —S(═O)—NRR claim 1 , Calkyl substituted with —NH—S(═O)—C-alkyl claim 1 , Calkyl substituted with —NH—S(═O)-haloCalkyl or Calkyl substituted with —NH—S(═O)—NRR.3. A compound according to wherein each Ris hydrogen.4. A compound according to wherein Rrepresents Calkyl.5. A compound according ...

Processes For The Preparation Of A Diarylthiohydantoin Compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer. 3. The process of claim 2 , wherein the solvent is diglyme claim 2 , dioxane claim 2 , butyronitrile claim 2 , or propionitrile.4. The process of claim 3 , wherein compound (VII) is reacted in the presence of norbornadiene claim 3 , tetrabutylammonium bromide claim 3 , and DABCO.6. The process of claim 5 , wherein the palladium catalyst is added to the reaction mixture as a pre-formed palladium catalyst or is generated in situ.12. The process of claim 11 , wherein the organomagnesium halide is a Calkylmagnesium halide or a Ccycloalkylmagnesium halide; wherein the lithium halide is lithium chloride claim 11 , lithium bromide claim 11 , or lithium iodide; and the aprotic organic solvent is tetrahydrofuran claim 11 , 2-methyl-tetrahydrofuran claim 11 , methyl tert-butylether (MTBE) claim 11 , cyclopentyl methylether (CPME) claim 11 , or toluene.13. The process of claim 12 , wherein the Calkylmagnesium halide is a Calkylmagnesium chloride or Calkylmagnesium bromide and the Ccycloalkylmagnesium halide is a Ccycloalkylmagnesium chloride or a Ccycloalkylmagnesium bromide.14. The process of wherein the Calkylmagnesium halide is isopropylmagnesium chloride claim 12 , sec-butylmagnesium chloride claim 12 , n-pentylmagnesium chloride claim 12 , hexylmagnesium chloride claim 12 , ethylmagnesium chloride claim 12 , ethylmagnesium bromide claim 12 , n-butylmagnesium chloride claim 12 , or isopropylmagnesium chloride and the Ccycloalkylmagnesium halide is cyclohexylmagnesium chloride.19. The process of claim 10 , wherein compound (1c) is converted to compound (X) by reacting compound (1c) with methylamine in a solvent claim 10 , in the presence of a coupling agent claim 10 , to yield compound (X).20. The method of claim 19 , wherein the coupling agent is 1 claim 19 ,1′-carbonyldiimidazole (CDI) and the solvent is tetrahydrofuran ...

PYRAZOLYL QUINOXALINE KINASE INHIBITORS

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer. 143.-. (canceled)46. A process according to claim 45 , wherein the prepared compound of formula (I) is N-(3 claim 45 ,5-Dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1 claim 45 ,2-diamine.48. A process according to claim 47 , wherein the prepared compound of formula (I) is N-(3 claim 47 ,5-Dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1 claim 47 ,2-diamine. This application is a divisional application of U.S. application Ser. No. 14/505,020, filed on Oct. 2, 2014 (published as US 2015-0105368 A1 on Apr. 16, 2015), which is a divisional application of U.S. application Ser. No. 13/643,741 (published as US 2013-0072457 A1 on Mar. 21, 2013), which is a national stage filing under section 371 of International Application No. PCT/GB2011/050851, filed on Apr. 28, 2011, and published in English on Nov. 3, 2011, as WO 2011/135376, and claims priority to British Application No. 1007286.6 filed on Apr. 30, 2010, and to U.S. Provisional Application No. 61/329,884, filed on Apr. 30, 2010. The entire disclosures of each of the prior applications are hereby incorporated herein by reference.The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.According to a first aspect of the invention there is provided compounds of formula (I):including any tautomeric or stereochemically isomeric form thereof, whereinIn one embodiment there is provided compounds of formula (I):including any stereochemically isomeric form thereof, whereinWO2006/092430, WO2008/003702, WO01/68047 ...

Process For The Preparation Of A Diarylthiohydantoin Compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer. 2. The process of claim 1 , comprising:reacting compound VII with an organomagnesium halide; in the presence or absence of a lithium halide; andadding carbon dioxide gas; in an aprotic organic solvent; at a temperature of about 0° C. to yield compound 1c.3. The process of claim 1 , comprising reacting compound VII under a carbon monoxide atmosphere; in the presence of a palladium catalyst; in the presence of one or more phosphorus ligands; in the presence of water; in a solvent; at a temperature of about 0° C. to about 100° C. to yield the compound 1c. This application is a continuation of U.S. patent application Ser. No. 16/427,637, filed May 31, 2019, which is a continuation of U.S. patent application Ser. No. 15/537,859, filed Jun. 19, 2017, which is the U.S. national stage of International Patent Application No. PCT/US2015/066345, filed Dec. 17, 2015, which claims priority to U.S. Provisional Patent Application No. 62/094,425, filed Dec. 19, 2014, all disclosures of which are hereby incorporated by reference in their entireties.The research and development of the invention described below was not federally sponsored.The present invention is directed to the preparation of compound (X) and intermediates in its synthesis. More specifically, the present invention is directed to processes for the preparation of compound (X), disclosed in U.S. Pat. No. 8,445,507, issued on May 21, 2013, which is hereby incorporated by reference in its entirety.Compound (X) of the present invention is currently being investigated for use in the treatment of prostate cancer. The present invention describes processes and intermediates for the preparation of such compound.The present invention is directed to a process for the preparation of compound (X)Comprising, consisting of, and/or consisting essentially ofreacting compound (V) with ...

Process for the preparation of a diarylthiohydantoin compound

Imidazo[1,2-b]pyridazine derivatives and their use as PDE10 inhibitors

The present invention relates to novel imidazo[1,2- b ]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.

Novel mandelate salts of substituted tetracyclic tetrahydrofuran derivatives

THE OBJECT OF THE PRESENT INVENTION IS A NOVEL MANDELATE SALT OF A SUBSTITUTED TETACYCLIC TETRAHYDROFURAN DERIVATIVE ACCORDING TO FORMULA (1) THE N-OXIDE FORMS AND THE STEREOCHEMICALLY ISOMERIC FORMS THEREOF, WHEREIN R¹ AND R² EACH INDEPENDENTLY ARE HYDROGEN OR C1-6 ALKYL AND R³ AND R⁴ EACH INDEPENDENTLY ARE HYDROGEN OR HALOGEN. IN THE FOREGOING DEFINITIONS C1-6ALKYL DEFINES STRAIGHT AND BRANCHED SATURATED HYDROCARBON RADICALS HAVING FROM 1 TO 6 CARBON ATOMS SUCH AS, FOR EXAMPLE, METHYL, ETHYL, PROPYL, BUTYL, 1-METHYLPROPYL, 1, 1-DIMENTHYLETHYL, PEMTHYL OR HEXYL. THE NOVEL MANDELATE SALT IS NOT LIGHT-SENSITIVE AND IS FAR MORE STABLE THAN THE PRIOR ART SALTS AT ROOM TEMPERATURE, ENHANCED TEMPERATURE AND AT RELATIVE HIGH HUMIDITIES AND IN AQUEOUS MEDIA. ALSO DISCLOSED ARE PHARMACEUTICAL COMPOSITIONS COMPRISING MANDELATE SALTS ACCORDING TO THE INVENTION, MANDELATE SALTS ACCORDING TO THE INVENTION FOR USE AS A MEDICINE, A PROCESS FOR PREPARING THE MANDELATE SALTS ACCORDING TO THE INVENTION AND THE USE OF THE MANDELATE SALTS AND PHARMACEUTICAL COMPOSITIONS COMPRISING MANDELATE SALTS ACCORDING TO THE INVENTION FOR THE TREATMENT OR THE PREVENTION OF CNS DOSORDERS, CARDIOVASCULAR DISORDERS AND GASTROINTESTINAL DISORDERS.

Novel mandelate salts of substituted tetracyclic tetrahydrofuran derivatives

Pyrazolyl quinoxaline kinase inhibitors

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Pyrazolyl quinoxaline kinase inhibitors

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Pyrazolyl quinoxaline kinase inhibitors

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Process for the preparation of a diarylthiohydantoin compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

Imidazo[1,2-b]pyridazine derivatives and their use as pde10 inhibitors

The present invention relates to novel imidazo[1,2-b]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.

PYRAZOLYL-QUINOXALINE KINASE INHIBITOR COMPOUND, COMBINATION, PRODUCT, PROCESS FOR PREPARING A COMPOUND, PHARMACEUTICAL COMPOSITION, AND, USE OF A COMPOUND

COMPOSTO PIRAZOLIL-QUINAZOLINA INIBIDORES DE QUINASE, COMBINAÇÃO, PRODUTO, PROCESSO PARA A PREPARAÇÃO DE UM COMPOSTO, COMPOSIÇÃO FARMACÊUTICA, USO DE UM COMPOSTO, E, MÉTODO. A invenção refere-se aos novos compostos derivados de quinoxalina, às composições farmacêuticas compreendendo ditos compostos, aos processos para a preparação de ditos compostos e ao uso de ditos compostos no tratamento de doenças, p.ex., câncer. PYRAZOLYL-QUINAZOLINE COMPOUND KINASE INHIBITORS, COMBINATION, PRODUCT, PROCESS FOR PREPARING A COMPOUND, PHARMACEUTICAL COMPOSITION, USE OF A COMPOUND, AND, METHOD. The invention relates to novel quinoxaline-derived compounds, pharmaceutical compositions comprising said compounds, processes for the preparation of said compounds and the use of said compounds in the treatment of diseases, e.g. cancer.

Novel mandelate salts of substituted tetracyclic tetrahydrofuran derivatives

PROCEDURE FOR THE PREPARATION OF A DIARYLTHIOHYDANTO COMPOUND

Imidazo[1,2-b]pyridazine derivatives and their use as PDE10 inhibitors

The present invention relates to novel imidazo[1,2-b]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.

Pyrazolyl quinoxaline kinase inhibitors

Amide coupling process

The present invention relates to a synthetic process for amide coupling between a trihaloketone and an electron poor nucleophile, amenable to large scale synthesis, in particular, through a catalytic process.

Pyrazolyl quinoxaline kinase inhibitors

Disclosed are 3-(1-methylpyrazole-4-yl)-6-([phenyl]-alkyl-amino)-quinoxaline derivatives as represented by the general formula (I) including any tautomeric or stereochemically isomeric form thereof, a N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, wherein n represents an integer equal to 0, 1, 2, 3 or 4; R1 represents hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, hydroxyhaloalkyl, cyanoalkyl, alkoxyalkyl wherein each alkyl may optionally be substituted; each R1a is independently selected from hydrogen, alkyl, hydroxyalkyl, alkyl substituted with amino or mono- or di(alkyl)amino or -NH(cycloalkyl), cyanoalkyl, alkoxyalkyl, and alkyl substituted with one or more fluoro atoms; R3 represents hydroxyl, alkoxy, hydroxyalkoxy, alkoxy substituted with -NR10R11, alkyl, alkenyl, alkynyl, haloalkyl optionally substituted with -O-C(=O)-alkyl, hydroxyalkyl optionally substituted with -O-C(=O)-alkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyhaloalkyl, cyanoalkyl, alkyl substituted with carboxyl, alkyl substituted with -C(=O)-alkyl, alkyl substituted with -C(=O)-O-alkyl, alkyl substituted with alkoxyalkyl-O-C(=O)-, alkyl substituted with alkoxyalkyl-C(=O)-, alkyl substituted with -O-C(=O)-alkyl, alkoxyalkyl wherein each alkyl may optionally be further substituted; and wherein the remaining substituent are as defined herein. Representative compounds include 3-(1-methylpyrazol-4-yl)-6-([2-chloro-3,5-dimethoxy-phenyl]-ethyl-amino)-quinoxaline, 3-(1-methylpyrazol-4-yl)-6-([3,5-dimethoxy-phenyl]-(3-[S-2-hydroxymethyl-pyrrolindin-1-yl]propyl)-amino)-quinoxaline hydrochloride, 3-(pyrazol-4-yl)-6-([3,5-dimethoxy-phenyl]-([pyrrolindin-1-yl]propyl)-amino)-quinoxaline hydrochloride, 3-(1-(2-hydroxyethyl)-pyrazol-4-yl)-6-([3,5-dimethoxy-phenyl]-(3-aminopropyl)-amino)-quinoxaline, 3-(1-methyl-pyrazol-4-yl)-6-([3,5-dimethoxy-phenyl]-(2-hydroxy-3-methylbutyl)-amino)-quinoxaline and 3-(1-methylpyrazol-4-yl)-6-([3,5-dimethoxy-phenyl]-(3-(isopropylamino)-2- ...

Mono-hydrochloric salts of an inhibitor of histone deacetylase

This invention provides novel crystalline forms of mono-HCl salts and a mono-HCl salt hydrate of JNJ-26481585, an inhibitor of histone deacetylases. The invention also relates to processes for production of these forms, to intermediates used in these processes, to pharmaceutical compositions comprising these forms, and to the use of these forms in medical treatment for instance as a medicine to inhibit proliferative conditions, such as cancer and leukemia.

Mono-hydrochloric salts of an inhibitor of histone deacetylase

IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES AND THEIR USE AS PDE10 INHIBITORS

Pyrazolyl quinoxaline kinase inhibitors

Abstract The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said 5 compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Processes for the preparation of a diarylthiohydantoin compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

Pyrazolyl quinoxaline kinase inhibitors

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Polymorphic and hydrate forms, salts and process for preparing 6-{difluoro[6-(1-methyl-1h-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline

Pyrazolyl quinoxaline kinase inhibitors

Pyrazolyl quinoxaline kinase inhibitors

Process for the preparation of a diarylthiohydantoin compound

Process for the preparation of a diarylthiohydantoin compound

Mono-hydrochloric salts of an inhibitor of histone deacetylase

This invention provides novel crystalline forms of mono-HCl salts and a mono-HCl salt hydrate of JNJ-26481585, an inhibitor of histone deacetylases. The invention also relates to processes for production of these forms, to intermediates used in these processes, to pharmaceutical compositions comprising these forms, and to the use of these forms in medical treatment for instance as a medicine to inhibit proliferative conditions, such as cancer and leukemia.

Process for the preparation of a diarylthiohydantoin compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

Mono-hydrochloric salts of an inhibitor of histone deacetylase.

La presente invención provee formas cristalinas novedosas de sales mono-HCI y una sal hidrato mono-HCI de JNJ-2648 1585, un inhibidor de histona deacetilasa; la invención se refiere, además, a procesos para la producción de dichas formas, a intermediarios utilizados en dichos procesos, a composiciones farmacéuticas que comprenden dichas formas, y a la utilización de dichas formas en un tratamiento médico, por ejemplo, como medicamento para inhibir afecciones proliferativas, tales como cáncer y leucemia.

Pyrazolyl quinoxaline kinase inhibitors

Pyrazolyl quinoxaline kinase inhibitors

Pyrazolyl quinoxaline kinase inihibitors

THE INVENTION RELATES TO NEW QUINOXALINE DERIVATIVE COMPOUNDS, TO PHARMACEUTICAL COMPOSITIONS COMPRISING SAID COMPOUNDS, TO PROCESSES FOR THE PREPARATION OF SAID COMPOUNDS AND TO THE USE OF SAID COMPOUNDS IN THE TREATMENT OF DISEASES, E.G. CANCER. (NO FIGURE)

Pyrazolyl quinoxaline kinase inhibitors

Processo para a preparação de um composto de diaril tio-hidantoína

PROCESSO PARA A PREPARAÇÃO DE UM COMPOSTO DE DIARIL TIOHIDANTOÍNA. A presente invenção se refere aos processos e intermediários para a preparação do composto (X) que está atualmente sendo investigado para o tratamento de câncer de próstata.

Synthesis of 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1h-indol-2 yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2h-imidazo[4,5-c]pyridin-2-one

Αναστολεις πυραζολυλο κινοξαλινο κινασης

Η εφεύρεση αναφέρεται σε νέες ενώσεις παραγώγων κινοξαλίνης, σε φαρμακευτικές συνθέσεις που περιλαμβάνουν τις εν λόγω ενώσεις, σε μεθόδους για την παρασκευή των αναφερθεισών ενώσεων και στη χρήση των αναφερθεισών ενώσεων στη θεραπεία νόσων, π.χ. του καρκίνου.

Processes for the preparation of a diarylthiohydantoin compound

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.

Μεθοδος για την παρασκευη μιας ενωσης διαρυλθειοϋδαντοϊνης

Αποκαλυπτόμενες είναι μέθοδοι και ενδιάμεσα για την παρασκευή ένωσης (Χ), η οποία σήμερα είναι υπό έρευνα για τη θεραπεία καρκίνου του προστάτη.

Process for the preparation of a diarylthiohydantoin compound

Disclosed are processes and intermediates for the preparation of Diarylthiohydantoin compound (X), which is currently being investigated for the treatment of prostate cancer.

Μεθοδος για την παρασκευη μιας ενωσης διαρυλθειοϋδαντοϊνης

Αποκαλυπτόμενες είναι μέθοδοι και ενδιάμεσα για την παρασκευή ένωσης (Χ), η οποία σήμερα είναι υπό έρευνα για τη θεραπεία καρκίνου του προστάτη.

Sintesis de 3-({5-cloro-1-[3-(metilsulfonil)propil]-1h-indol-2-il} metil)-1-(2,2,2-trifluoroetil)-1,3-dihidro-2h-imidazo[4,5-c]pirid in-2-ona.

La presente invención se refiere a una ruta de síntesis química para preparar el compuesto inhibidor del VRS 3-({5-cloro-1-[3-(met ilsulfonil)propil]-1H-indol-2-il}metil)-1-(2,2,2-trifluoroetil)-1 0 1,3-dihidro-2H-imidazo[4,5-c]piridin-2-ona, y a nuevos compuestos utilizados como compuestos intermedios en el proceso de múltiples pasos.

Síntesis de 3-({5-cloro-1-[3-(metilsulfonil)propil]-1h-indol-2-il}metil)-1-(2,2,2-trifluoroetil)- 1,3-dihidro-2h-imidazo[4,5-c]piridin-2-ona.

Μεθοδοι για την παρασκευη μιας ενωσης διαρυλθειοϋδαντοϊνης

Αποκαλυπτόμενες είναι μέθοδοι και ενδιάμεσα για την παρασκευή ένωσης (Χ), η οποία σήμερα είναι υπό έρευνα για τη θεραπεία καρκίνου του προστάτη.

Composto pirazolil-quinoxalina inibidor de quinase, combinação, produto, processo para a preparação de um composto, composição farmacêutica, uso de um composto, e método

composto pirazolil-quinazolina inibidores de quinase, combinação, produto, processo para a preparação de um composto, composição farmacêutica, uso de um composto, e, método. a invenção refere-se aos novos compostos derivados de quinoxalina, às composições farmacêuticas compreendendo ditos compostos, aos processos para a preparação de ditos compostos e ao uso de ditos compostos no tratamento de doenças, p.ex., câncer.

Αναστολεις πυραζολυλο κινοξαλινο κινασης

Η εφεύρεση αναφέρεται σε νέα παράγωγα κινοξαλίνης, σε φαρμακευτικές συνθέσεις που περιλαμβάνουν τις εν λόγω ενώσεις, σε μεθόδους για την παρασκευή των εν λόγω ενώσεων και στη χρήση των εν λόγω ενώσεων στη θεραπεία ασθενειών π.χ. του καρκίνου.

Αναστολεις πυραζολυλο κινοξαλινο κινασης

Η εφεύρεση αναφέρεται σε νέες ενώσεις παραγώγων κινοξαλίνης, σε φαρμακευτικές συνθέσεις που περιλαμβάνουν τις εν λόγω ενώσεις, σε διαδικασίες για την παρασκευή των εν λόγω ενώσεων και στη χρήση των εν λόγω ενώσεων στη θεραπεία νόσων, π.χ. καρκίνος.

Inhibitori kinaze priazolil kinoksalina

Síntese de 3-({5-cloro-1-[3-(metilsulfonil)propil]-1h-indol-2-il}metil)-1-(2,2,2-trifluoroetil)-1,3-di-hidro-2h-imidazo[4,5-c]piridin-2-ona

SÍNTESE DE 3-({5-CLORO-1-[3-(METILSULFONIL)PROPIL]-1H-INDOL-2-IL}METIL)-1-(2,2,2-TRIFLUOROETIL)-1,3-DI-HIDRO-2H-IMIDAZO[4,5-C]PIRIDIN-2-ONA. A presente invenção refere-se a uma via de síntese química para preparar o composto inibidor de RSV 3-({5-cloro-1-[3-(metilsulfonil)propil]-1H-indol-2-il}metil)-1-(2,2,2-trifluoroetil)- 1,3-di-hidro-2H-imidazo[4,5-c]piridin-2-ona e a novos compostos usados como compostos intermediários no processo multietapa.