The present invention relates to a liquid formulation comprising a VEGF receptor fusion protein at a concentration of at least 100 mg/ml, and wherein the formulation comprises: i) no buffering agent, ii) a citrate buffer, or iii) a histidine buffer preferably without sucrose and preferably with methionine. In addition, the invention relates to an article of manufacture comprising a container with such liquid formulation as well as the use of the liquid formulation for a method of treatment.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
2.
Stabilization of Pharmaceutical Compositions Comprising Polysorbate
The present invention relates to stabilized pharmaceutical compositions comprising an improved histidine-based buffer system that reduces the degradation of polysorbates.
The present invention relates to a liquid formulation comprising a VEGF receptor fusion protein at a concentration of at least 100 mg/ml, and wherein the formulation comprises: i) no buffering agent, ii) a citrate buffer, or iii) a histidine buffer preferably without sucrose and preferably with methionine. In addition, the invention relates to an article of manufacture comprising a container with such liquid formulation as well as the use of the liquid formulation for a method of treatment.
The present invention belongs to the field of biotechnology, and specifically relates to recombinant gene expression. The invention concerns a method of recombinant gene expression from a Chinese Hamster Ovary (CHO) cell, by using super-enhancer sequences for increased gene expression. Thus, the invention provides a method for producing an engineered CHO cell by introducing into the cell an exogenous nucleic acid molecule into or within 500 kb upstream or downstream of a super-enhancer as expression-enhancing sequence. The invention further provides an engineered CHO cell produced by the method. The invention further provides a method of producing a recombinant polypeptide. The invention is further directed to the use of a super-enhancer for transgene expression.
RRHH-benzo[d]imidazol-2-yl)- 1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (INN: glasdegib) and a process of producing the same. Furthermore, the invention relates to a pharmaceutical composition comprising the dimaleate form of glasdegib and at least one pharmaceutically acceptable excipient. The pharmaceutical composition of the present invention can be used as a medicament, in particular for the treatment and/or prevention of cancers such as acute myeloid leukemia.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
6.
STABILIZATION OF PHARMACEUTICAL COMPOSITIONS COMPRISING POLYSORBATE
The present invention relates to stabilized pharmaceutical compositions comprising an improved histidine-based buffer system that reduces the degradation of polysorbates.
The invention relates to crystalline upadacitinib phosphate, especially of formula (II), and a process for preparing the same. The invention also relates to a pharmaceutical composition comprising crystalline upadacitinib phosphate, preferably in a predetermined and/or effective amount and at least one pharmaceutically acceptable excipient. The pharmaceutical composition of the invention can be used as a medicament, in particular for the treatment and/or prophylaxis of rheumatoid arthritis. (ll) n is in the range of from 1.8 to 2.2.
The present invention relates to acetic acid solvates of upadacitinib and processes for their preparation. The invention also relates to a pharmaceutical composition comprising an upadacitinib acetic acid solvate, preferably in a predetermined and/or effective amount and at least one pharmaceutically acceptable excipient. The pharmaceutical composition of the present invention can be used as a medicament, in particular for the treatment and/or prophylaxis of rheumatoid arthritis.
The present invention relates in general to the field of recombinant protein expression. In particular, the present invention relates to a method for selecting a suitable candidate cell clone for recombinant protein expression and to a host cell for recombinant protein expression, the host cell exhibiting artificially modified gene expression of at least one gene selected from the group consisting of: Fkbp10, ZdhhC6, Myrip, Actc1, AC124993.19, Runx2, AC158560.4, PlekhB1, Rps6KA2, Sept1, Sprr2k, and Flt1.
The present invention relates in general to the field of recombinant protein expression. In particular, the present invention relates to a method for selecting a suitable candidate cell clone for recombinant protein expression and to a host cell for recombinant protein expression, the host cell exhibiting artificially modified gene expression of at least one gene selected from the group consisting of: Hist1h2bc, Egrl, BX842664.2/Hist 1h3c, Dhfr, Fgfr2, AC115880.11, Mmp10, Vsnll (optional), CU459186.17, El 30203 B14Rik, Cspg4, C1qtnf1, Foxp2, and Ptpre.
The invention relates to novel hydrates of dolutegravir sodium and to processes for their preparation. Furthermore, the invention relates to a novel crystalline form of dolutegravir sodium, which is a useful intermediate for the preparation of one of the novel hydrates. In addition, the invention relates to the use of the novel hydrates for the production of pharmaceutical compositions. Finally, the invention relates to pharmaceutical compositions comprising an effective amount of the novel hydrates, to oral dosage forms comprising said pharmaceutical compositions, to a process for preparing said oral dosage forms, and to the use of said pharmaceutical compositions or dosage forms in the treatment of retroviral infections such as HIV-1 infections.
The present invention relates to an efficient route of synthesis of solithromycin and to a method of its purification which obviates the necessity of chromatographic purifications and improves the quality of the product by efficiently removing impurities.
The present invention relates to processes for preparing β-aminosulfone compounds. The provided compounds are useful intermediates in the preparation of sulfone group containing isoindoline-based compounds, in particular apremilast.
C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
C07C 315/04 - Preparation of sulfonesPreparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
C07C 319/18 - Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by addition of thiols to unsaturated compounds
C07C 315/02 - Preparation of sulfonesPreparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
14.
PEG-BASED DENDRON AND PROCESS FOR PRODUCING THE SAME
It is provided a process for preparing biodegradable dendrons based on poly(ethyleneglycol) (PEG), as well as novel biodegradable dendrons based on PEG. The present invention also provides conjugates of the biodegradable dendrons of the present invention with biomolecules and conjugates for use as medicaments.
The present invention relates to an asymmetric process for providing N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide (apremilast) or a pharmaceutically acceptable salt or solvate thereof.
The present invention relates to a process for providing a chiral β-hydroxysulfone compound, an intermediate useful in the synthesis of the isoindoline-based compound apremilast.
The present invention relates to 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine acetate in crystalline form and to methods for the preparation thereof. In addition the present invention relates to solid pharmaceutical compositions for oral administration comprising an effective amount of the crystalline 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine acetate. Moreover, the present invention relates to the use of crystalline 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine acetate for the preparation of pharmaceutical compositions.
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
The present invention relates to processes for preparing substances with antiviral activity, in particular the integrase inhibitors dolutegravir and cabotegravir and analogues thereof, as well as intermediates useful in the processes.
The present invention is related to a cell culture medium for reducing the C-terminal heterogeneity of a polypeptide expressed in cell-culture, wherein the medium comprises at least one essential trace element in an effective amount, and to a cell culture process for reducing C-terminal heterogeneity of a protein, in which process an essential trace element is used.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
20.
NOVEL SOLVATES OF N-[2-[(1S)-1-(3-ETHOXY-4-METHOXYPHENYL)-2-(METHYLSULFONYL)ETHYL]-2,3-DIHYDRO-1,3-DIOXO-1H-ISOINDOL-4-YL]ACETAMIDE
The present invention relates to novel crystalline solvates of N-[2-[(1S)-1-(3-ethoxy-4- methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide and methods for their preparation. Furthermore, the invention concerns pharmaceutical compositions comprising an effective amount of one or more of the novel crystalline solvates and the use thereof as medicaments.
The present invention relates to non-stoichiometric crystalline hydrates of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, processes for their preparation, and their use as medicaments. In addition the present invention relates to pharmaceutical compositions comprising an effective amount of the novel crystalline hydrates.
C07D 409/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
A61K 31/7034 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
22.
PREDICTING GENETICALLY STABLE RECOMBINANT PROTEIN PRODUCTION IN EARLY CELL LINE DEVELOPMENT
The present invention relates in general to the field of recombinant protein expression. In particular, the present invention relates to a method for selecting a suitable candidate cell clone for recombinant protein expression and to a host cell for recombinant protein expression, the host cell exhibiting artificially modified gene expression of at least one gene selected from the group consisting of: Hist1h2bc, Egrl, BX842664.2/Hist 1h3c, Dhfr, Fgfr2, AC115880.11, Mmp10, Vsnll (optional), CU459186.17, El 30203 B14Rik, Cspg4, C1qtnf1, Foxp2, and Ptpre.
The present invention relates in general to the field of recombinant protein expression. In particular, the present invention relates to a method for selecting a suitable candidate cell clone for recombinant protein expression and to a host cell for recombinant protein expression, the host cell exhibiting artificially modified gene expression of at least one gene selected from the group consisting of: Fkbp10, ZdhhC6, Myrip, Actc1, AC124993.19, Runx2, AC158560.4, PlekhB1, Rps6KA2, Sept1, Sprr2k, and Flt1.
The present invention relates to a process for spray-freeze-drying (SFD) a dispersion of polyelectrolyte complex (PEC) nanoparticles loaded with a protein drug, which yields a powdered product with adequate flowability properties that may readily be processed further into solid dosage forms such as tablets or capsules. The mean particle size of PEC nanoparticles obtained after redispersion of SFD powder or pharmaceutical compositions made from said powder in water is preserved in the nanometer range (< 1000 nm), and so is the protein biological activity.
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.
C07C 319/20 - Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
C07C 323/37 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring the thio group being a sulfide group the sulfur atom of the sulfide group being further bound to a carbon atom of a six-membered aromatic ring
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
C07C 323/09 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
The invention relates to novel hydrates of dolutegravir sodium and to processes for their preparation. Furthermore, the invention relates to a novel crystalline form of dolutegravir sodium, which is a useful intermediate for the preparation of one of the novel hydrates. In addition, the invention relates to the use of the novel hydrates for the production of pharmaceutical compositions. Finally, the invention relates to pharmaceutical compositions comprising an effective amount of the novel hydrates, to oral dosage forms comprising said pharmaceutical compositions, to a process for preparing said oral dosage forms, and to the use of said pharmaceutical compositions or dosage forms in the treatment of retroviral infections such as HIV-1 infections.
A61K 31/5365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
The present invention relates to processes for preparing β-aminosulfone compounds. The provided compounds are useful intermediates in the preparation of sulfone group containing isoindoline-based compounds, in particular apremilast.
C07C 315/04 - Preparation of sulfonesPreparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
C07C 317/28 - SulfonesSulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
C07C 317/16 - SulfonesSulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
28.
STEREOSELECTIVE SYNTHESIS OF INTERMEDIATES IN THE PREPARATION OF ß-C-ARYLGLUCOSIDES
The invention belongs to the fields of pharmaceutical industry, and particularly to an improved stereoselective synthesis of intermediate compounds for the preparation of gliflozins, for example canagliflozin or structurally similar gliflozins. Gliflozins, such as canagliflozin, dapagliflozin, empagliflozin, or ipragliflozin, inhibit the sodium-dependent glucose cotransporter 2 (SGLT2) in the kidney and as such are useful in the treatment of type-2 diabetes.
C07D 407/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
The present invention relates to a novel crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, to a process for its preparation and to its use for the purification of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene.
C07D 409/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
30.
SYNTHESIS OF VORTIOXETINE VIA (2,4-DIMETHYLPHENYL)(2-IODOPHENYL)SULFANE INTERMEDIATE
The present invention provides a new synthetic process for the production of 1 -(2-((2,4-dimethylphenyl)thio)phenyl)piperazine (vortioxetine), a drug for the treatment of depression and anxiety, which is conducted via (2,4-dimethylphenyl)(2-iodophenyl)sulfane intermediate.
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
The present invention belongs to the field of pharmaceutical industry and relates to a solid pharmaceutical composition comprising androgen receptor antagonists, e.g. Enzalutamide or ARN-509, as well as to processes for preparing the same. The solid pharmaceutical compositions are useful in the treatment of prostate cancer.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
The present invention provides a new synthetic process for the production of 1-(2-((2,4- dimethylphenyl)thio)phenyl)piperazine (vortioxetine), a drug for the treatment of depression and anxiety, which is conducted via (2-(piperazine-1-yl)phenyl)aniline intermediates.
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
The present invention relates to amorphous adducts of ticagrelor with divalent metal salts useful in the treatment or prevention of arterial thrombotic complications in patients with coronary artery, cerebrovascular or peripheral vascular disease.
This invention is in the field of protein pegylation. In particular, it relates to a method for pegylating therapeutic proteins. The invention also relates to the use of such pegylated therapeutic polypeptides for treating muscle diseases and disorders.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 14/65 - Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
35.
SYNTHESIS OF VORTIOXETINE VIA (2-(PIPERAZINE-1 -YL)PHENVL)LITHIUM INTERMEDIATES
The present invention provides a new synthetic process for the production of 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine (vortioxetine), a drug for the treatment of depression and anxiety, which is conducted via (2-(piperazine-1-yl)phenyl)lithium intermediates.
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
36.
Synthetic route for the preparation of β-aminobutyryl substituted 5,6,7,8-tetrahydro[1,4]diazolo[4,3-alpha ]pyrazin-7-yl compounds
C07D 205/08 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
C07C 227/18 - Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
The present invention providesstabilized amorphous lorcaserin hydrochloride ((R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]- azepinehydrochloride), a pharmaceutical composition comprising the same, as well as a process for obtaining the same.
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
The present invention is related to a method to reduce peptide amidation activity in a given cell line, cell lines with reduced peptide amidation activity, and uses thereof.
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
The present invention relates to novel polymers, which exhibit improved association with protein drugs and enable the formation of nanoparticles (NPs) with high protein loading.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 51/12 - Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes
C08G 69/48 - Polymers modified by chemical after-treatment
40.
NANOFORMULATION OF G-CSF FOR NON-PARENTERAL DELIVERY
The present invention relates to erythropoietin (EPO) conjugates having a high bioavailability and efficacy, especially when administered perorally. Also provided are methods for preparing the EPO conjugates, their use for treating various diseases, and pharmaceutical compositions comprising said EPO conjugates, alone or in combination with absorption enhancers and/or coating polymers.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
The present invention relates to compositions comprising erythropoietin, one or more absorption enhancers and/or one or more bioadhesive polymers for oral administration.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
The present invention is related to a cell culture medium for reducing the C-terminal heterogeneity of a polypeptide expressed in cell-culture, wherein the medium comprises at least one essential trace element in an effective amount, and to a cell culture process for reducing C-terminal heterogeneity of a protein, in which process an essential trace element is used.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
The present invention provides a very simple, efficient and economic technology for racemisation of amines, alcohols or thioalcohols where the chiral carbon (benzylic position) is located at the β-position of the heteroatom (amino, hydroxyl or mercapto group) or even more distant therefrom. Special focus is oriented in efficient and simple racemisation of an undesired enantiomer of a chiral pharmaceutically active ingredient, preferably lorcaserin or a salt thereof, preferably the hydrochloride salt thereof. The approach according to the invention enables a use of cheaper and shorter racemic synthetic schemes not requiring expensive and toxic reagents and catalysts. Present methodology enables industrialy convenient process.
C07C 33/20 - Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part monocyclic
C07C 271/14 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups
C07C 211/27 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring having amino groups linked to the six-membered aromatic ring by saturated carbon chains
C07C 211/29 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
C07C 233/66 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
45.
1-[2-(2,4-DIMETHYLPHENYLSULFANYL) PHENYL]PIPERAZINE ACETATE IN CRYSTALLINE FORM
The present invention relates to 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine acetate in crystalline form and to methods for the preparation thereof. In addition the present invention relates to solid pharmaceutical compositions for oral administration comprising an effective amount of the crystalline 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine acetate. Moreover, the present invention relates to the use of crystalline 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine acetate for the preparation of pharmaceutical compositions.
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61P 25/00 - Drugs for disorders of the nervous system
46.
PREPARATION OF CHIRAL 1-METHYL-2,3,4,5-1H-BENZODIAZEPINES VIA ASYMMETRIC REDUCTION OF ALPHA-SUBSTITUTED STYRENES
The present invention provides an asymmetric and economic synthesis of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine via novel intermediates applying an asymmetric enzymatic, biomimetic or catalytic reduction. The present invention also provides a novel green asymmetric catalytic reduction adapted for an aqueous medium to be applied in the synthesis of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1 H-benzo[d]azepine or novel intermediates.
C07C 67/03 - Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
C07C 69/635 - Halogen-containing esters of saturated acids containing rings in the acid moiety
C07C 201/12 - Preparation of nitro compounds by reactions not involving the formation of nitro groups
C07C 205/09 - Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
C07C 209/34 - Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
C07C 209/48 - Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of nitriles
C07C 211/29 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
C07C 217/40 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the same carbon atom of the carbon skeleton, e.g. amino-ketals, ortho esters
C07C 233/18 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
C07C 253/30 - Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
C07C 255/10 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and halogen atoms, or nitro or nitroso groups, bound to the same acyclic carbon skeleton
C07C 311/17 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
47.
NEW PROCESS FOR THE SYNTHESIS OF 1-(2-((2,4-DIMETHYLPHENYL)THIO)PHENYL)PIPERAZINE
The present invention provides 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, which comprises the reaction of a compound of formula (VII), or salt thereof, (VII) wherein Q represents S, SO or SO2 and LG represents a leaving group, with a compound of formula (XI), or salt thereof, (XI) wherein Z represents hydrogen or a protecting group. New intermediate compounds are also provided.
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
48.
NOVEL SYNTHETIC PROCESSES TO 8-CHLORO-3-BENZO[D]AZEPINE VIA FRIEDEL-CRAFTS ALKYLATION OF OLEFIN
The present invention is directed to a short, facile, effective and industrially applicable process for obtaining 8-chloro-l-methyl-2,3,4,5-tetrahydro-lH- benzo[d]azepine, or its salt, preferably lorcaserin hydrochloride. The present invention is further directed to a simple and effective ring closing methodology for obtaining 8-chloro-l-methyl-2,3,4,5-tetrahydro-lH- benzo[d]azepine, or its salt, preferably lorcaserin hydrochloride. The present invention is also directed to a novel intermediate which can be suitably used in the process for producing 8-chloro-l-methyl-2, 3,4,5- tetrahydro-lH-benzo[d]azepine, or its salt, preferably lorcaserin hydrochloride and to a process for producing the novel intermediate.
The present invention relates to non-stoichiometric crystalline hydrates of 1-(ß-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene, processes for their preparation, and their use as medicaments. In addition the present invention relates to pharmaceutical compositions comprising an effective amount of the novel crystalline hydrates.
C07D 409/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
Title: New Solid Form of 1-(2-((2,4-Dimethylphenyl)thio)phenyl)piperazine Hydrobromide The present invention relates to 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine hydrobromide (vortioxetine hydrobromide,a drug for the treatment of depression and anxiety) in amorphous form and in association with an adsorbent. The invention further relates to pharmaceutical compositions comprising amorphous 1-(2-((2,4-dimethylphenyl)thio)phenyl)- piperazinehydrobromidein association with an adsorbent, processes for the manufacture of such pharmaceutical compositions and their use as medicaments.
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61P 25/00 - Drugs for disorders of the nervous system
51.
NOVEL SYNTHETIC PROCESS TO 8-CHLORO-1-METHYL-BENZO[D]AZEPINE, NOVEL INTERMEDIATES AND THE PRODUCTION THEREOF
The present invention is directed to a simple and economical process for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine via novel intermediates and a highly selective asymmetric synthesis leading to enantiopure (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d] azepine or its (S)-enantiomer, in order to avoid or overcome chemical optical resolution.
C07C 233/31 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
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.
C07C 323/37 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring the thio group being a sulfide group the sulfur atom of the sulfide group being further bound to a carbon atom of a six-membered aromatic ring
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
C07C 319/20 - Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
53.
Production of glycoproteins with low N-glycolylneuraminic acid (Neu5Gc) content
The present invention relates to a medium for the cultivation of eukaryotic cells, the medium comprising as (an) additive(s) DMSO, N-acetylmannosamine (NAcMan), N-acetylglucosamine (NAcGlc), or any combination of two or more of these additives, including the combination of NAcMan and NAcGlc.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention relates to the field of organic synthesis and describes the synthesis of specific triazolopyrimidine compounds and intermediates thereof as well as related derivatives.
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
55.
Production of glycoproteins with low N-glycolylneuraminic acid (NEU5GC) content
The present invention relates to a medium for the cultivation of eukaryotic cells, the medium comprising as (an) additive(s) DMSO, N-acetylmannosamine (NAcMan), N-acetylglucosamine (NAcGlc), or any combination of two or more of these additives, including the combination of NAcMan and NAcGlc.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07C 233/51 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
The present invention relates to the preparation of 3-amino-piperidine compounds via nitro-tetrahydropyridine precursors and salts thereof. These compounds can be used as intermediates in the synthesis of pharmaceutically active agents such as tofacitinib or derivatives thereof.
C07D 211/02 - Preparation by ring-closure or hydrogenation
C07D 225/06 - Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with one six-membered ring
C07D 211/48 - Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
C07D 211/72 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
A stable formulation of telmisartan and hydrochlorothiazide having both substances in separate units is prepared, exhibiting exceptional stability when subjecting to stress conditions.
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
A61K 31/549 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
C12N 1/38 - Chemical stimulation of growth or activity by addition of chemical compounds which are not essential growth factorsStimulation of growth by removal of a chemical compound
60.
NEW SYNTHETIC ROUTE FOR THE PREPARATION OF 3-AMINO-PIPERIDINE COMPOUNDS
The present invention relates in general to the field of organic chemistry and in particular to the preparation of 3-amino-piperidine compounds. These compounds can be used as intermediates in the synthesis of pharmaceutically active agents such as preferably tofacitinib or derivatives thereof, or further pharmaceutically active agents comprising as a structure a 3-aminopiperidine moiety.
C07D 211/72 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
The present invention relates to amorphous adducts of ticagrelor with divalent metal salts useful in the treatment or prevention of arterial thrombotic complications in patients with coronary artery, cerebrovascular or peripheral vascular disease.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
62.
GENOME SEQUENCE BASED TARGETED CLONING OF DNA FRAGMENTS
The present invention belongs to the field of molecular biology, microbiology and microbial genetics and specifies the plasmid rescue method for targeted cloning of DNA fragments from a donor organism into a host cell, comprising inter alia the steps of transferring a Bacterial Artificial Chromosome (BAC)-vector that comprises a site-specific recombination system containming an integrase and an attP site into a donor organism, wherein said donor organism does not contain a functional attB site. Further, the present invention refers to a plasmid rescue method for targeted cloning of DNA fragments from a donor organism into a host cell, comprising inter alia the steps of transferring a BAC-vector that comprises a site-specific recombination system containing an attP site however no functional integrase into a donor organism, wherein in a further step a functional integrase has to be introduced into a final host cell. Further, the present invention refers to a vector comprising inter alia a site-specific recombination system containing an attP site however no functional integrase, and to a vector comprising inter alia a site-specific recombination system containing an integrase and an attP site and a DNA sequence suitable for homologous recombination. The present invention further refers to the use of said vectors for cloning and/or transferring of a DNA fragment. Additionally, the present invention refers to suitable donor organisms comprising the BAC vectors according to the present invention, to an expression system comprising a host cell and a BAC vector, as well as to the use of said expression system for cloning and/or transfer of the DNA fragment, and /or for expression of said DNA fragment.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
C07D 205/08 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
64.
Process for the preparation of 3-aroyl-5-aminobenzofuran derivatives
The present invention relates to a process for the preparation of 3-aroyl-5-aminobenzofuran derivatives useful as antiarrhythmic drugs which avoids the use of nitro intermediates.
C07D 307/00 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
C07D 307/81 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
C07D 307/82 - Benzo [b] furansHydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
C07D 307/84 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
65.
Selection of triploid CHO cells and cell lines expressing recombinant polypeptides as high producers
The present invention relates to a method for selecting for cells or cell lines that produce a recombinant protein/polypeptide in high yields, the method allowing for the selection of high producer cells or cell lines in an early phase of cell line development, the method comprising the step of determining the nuclear DNA content of the cells or cell lines, wherein the level of the nuclear DNA content of the cells or cell lines positively correlates with the capacity of the cells or cell lines to produce the recombinant protein/polypeptide.
The present invention is related to a method to reduce peptide amidation activity in a given cell line, cell lines with reduced peptide amidation activity, and uses thereof.
The present invention relates to the field of organic chemistry, and in particular to the preparation of β-borated compounds. These β-borated compounds can be used as intermediates in the synthesis pharmaceutically active agents such as sitagliptin.
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.
C07C 209/56 - Preparation of compounds containing amino groups bound to a carbon skeleton by rearrangement reactions from carboxylic acids involving a Hofmann, Curtius, Schmidt, or Lossen-type rearrangement
69.
SYNTHESIS OF 2-(3,4-DIFLUOROPHENYL)CYCLOPROPANECARBOXYLIC ACID
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.
C07C 67/327 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groupsPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenolysis of functional groups by elimination of functional groups containing oxygen only in singly bound form
C07C 45/68 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by isomerisationPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton by increase in the number of carbon atoms
C07C 51/08 - Preparation of carboxylic acids or their salts, halides, or anhydrides from nitriles
C07C 51/083 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid anhydrides
C07C 51/41 - Preparation of salts of carboxylic acids by conversion of the acids or their salts into salts with the same carboxylic acid part
C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
C07C 67/31 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
C07C 69/732 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
C07C 69/74 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
C07C 253/14 - Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
C07C 253/30 - Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
C07C 255/16 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same carbon atom of an acyclic carbon skeleton
C07C 255/30 - Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same unsaturated acyclic carbon skeleton
C07C 255/46 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
C07C 51/09 - Preparation of carboxylic acids or their salts, halides, or anhydrides from carboxylic acid esters or lactones
70.
PREPARATION OF OPTICALLY PURE ß-AMINO ACID TYPE ACTIVE PHARMACEUTICAL INGREDIENTS AND INTERMEDIATES THEREOF
The present invention relates to the preparation of optically resolved chiral compounds of β-amino acid type active pharmaceutical ingredients (API), more specifically to β-aminobutyryl substituted compounds and especially β-aminobutyryl compounds having γ-bound aryl groups. The present invention more particularly relates to the preparation of enantiomerically enriched chiral compounds useful as intermediates for the preparation of anti-diabetic agents, preferably sitagliptin.
C07C 211/27 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring having amino groups linked to the six-membered aromatic ring by saturated carbon chains
C07C 231/06 - Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups
C07C 239/20 - Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
C07C 227/34 - Preparation of optical isomers by separation of optical isomers
C07C 269/06 - Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
C07C 303/40 - Preparation of esters or amides of sulfuric acidsPreparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
C07C 67/31 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
71.
SYNTHESIS OF INTERMEDIATES FOR PREPARING ANACETRAPIB AND DERIVATIVES THEREOF
The present invention relates to the field of organic chemistry, more specifically to the synthesis of intermediate compounds which can be used in the synthesis of pharmaceutically active agents such as anacetrapib or derivatives thereof.
C07C 41/18 - Preparation of ethers by reactions not forming ether-oxygen bonds
C07C 41/20 - Preparation of ethers by reactions not forming ether-oxygen bonds by hydrogenation of carbon-to-carbon double or triple bonds
C07C 41/22 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogenPreparation of ethers by reactions not forming ether-oxygen bonds by substitution of halogen atoms by other halogen atoms
C07C 41/30 - Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
C07C 43/205 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
C07C 45/68 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by isomerisationPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton by increase in the number of carbon atoms
C07D 263/24 - Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
A61K 31/4166 - 1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.
C07D 239/46 - Two or more oxygen, sulfur or nitrogen atoms
C07D 317/44 - Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
The invention provides an inexpensive process for isolation of teicoplanin from a fermentation culture of Actinoplanes teichomyceticus in a grade for pharmaceutical application with substantial removal of colours. Applying optimal combination of cation and anion exchange techniques together with further improved purification affords a unique decoloured teicoplanin material. According to some embodiments, the glycopeptide antibiotic is eluted from the ion exchange column at a pH from 5 to below 9.
The invention relates to a process for purification of teicoplanin, in particular to a process for an efficient removal of impurities by means of adsorption of particular dissolved components from the filtrate of fermentation broth of Actinoplanes teichomyceticus culture on commercial hydrophobic or slightly polar adsorbent resins with further selective elution of the product from the resin. According to the invention, the process involves the use of a mixture of a watermiscible organic solvent in an aqueous solution at various steps of the purification process, such as in the above mentioned elution step and/or in an ultrafiltration step on membranes with a cut-off of 3-100kDa. The process further involves treating a teicoplanin solution with charcoal, e.g. after elution and before ultrafiltration. Preferably, the water-miscible organic solvent is selected from the group consisting of C1-C4 alcohols, C3-C4 ketones or C2-C4 nitrites.
The present invention relates to stable highly crystallineforms of anacetrapib, to processes for their preparation and to pharmaceutical compositions containing them.
C07D 263/04 - Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
The present invention belongs to the field of pharmaceutical industry and specifies the process for preparing clavulanic acid by using a microorganism, comprising the steps of providing a microorganism being capable of producing clavulanic acid and which produces d-(L-a-aminoadipyl)-L- cysteinyl-D-valine synthetase (ACVS), selectively reducing or abolishing ACVS activity by modifying or treating said microorganism, cultivating it and isolating clavulanic acid. Furthermore, the present invention refers to a process for preparing clavulanic acid by using said modified microorganism. Further, the present invention relates to a recombinant plasmid comprising a modified pcbAB gene, to a recombinant microorganism comprising said recombinant plasmid, and to the use of said recombinant plasmid for modifying a microorganism. Finally, the present invention also refers to a microorganism that is modified or treated by selectively reducing or abolishing activity of ACVS, as well as to the use of said microorganism for the production of clavulanic acid.
C12P 17/18 - Preparation of heterocyclic carbon compounds with only O, N, S, Se, or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
The present invention relates to the field of organic synthesis and describes the synthesis of specific triazolopyrimidine compounds and intermediates thereof as well as related derivatives.
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
The present invention relates to the field of organic synthesis and describes the synthesis of specific triazolopyrimidine compounds and intermediates thereof as well as related derivatives, suitable for the preparation of Ticagrelor (TCG).
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
The present invention relates to a pharmaceutical composition, preferably a pharmaceutical dosage form, comprising at least two separate compartments, wherein one compartment contains a composition comprising metformin or a pharmaceutically acceptable salt thereof and wherein another compartment contains a composition comprising sitagliptin.
c) combining the compositions to form compartments.
The present invention also refers to a process for preparing dosage forms comprising at least one compartment comprising metformin or a pharmaceutically acceptable salt thereof and sitagliptin or a pharmaceutically acceptable salt thereof, the process comprises providing a composition containing metformin or a pharmaceutically acceptable salt thereof, and sitagliptin or a pharmaceutically acceptable salt thereof, and a matrix agent.
Moreover, the present invention related to a dosage form obtained by said process, and to the use of said dosage form for the treatment of diabetes.
The invention relates to the preparation of chiral compounds, in particular to the preparation of chiral compounds which may be used as intermediates for the preparation of anti-diabetic agents, preferably sitagliptin.
C07C 229/34 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
C07C 239/20 - Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07C 311/19 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
C07F 7/10 - Compounds having one or more C—Si linkages containing nitrogen
C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
81.
PROCESS FOR THE PREPARATION OF α-SUBSTITUTED KETONES AND THEIR APPLICATION IN SYNTHESIS OF PHARMACEUTICALLY ACTIVE COMPOUNDS
The present invention relates to a novel one step preparation of 6-methoxy-2-phenyl-tetralone starting from 6-methoxy-tetralone and its use as an intermediate in the synthesis of pharmaceutically active compounds.
C07C 45/68 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by isomerisationPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton by increase in the number of carbon atoms
C07C 49/67 - Unsaturated compounds containing a keto group being part of a ring containing six-membered aromatic rings a keto group being part of a condensed ring system having two rings, e.g. tetralones
C07D 295/023 - PreparationSeparationStabilisationUse of additives
82.
Production of glycoproteins with low N-glycolylneuraminic acid (NEU5GC) content
The present invention relates to a medium for the cultivation of eukaryotic cells, the medium comprising as (an) additive(s) DMSO, N-acetylmannosamine (NAcMan), N-acetylglucosamine (NAcGlc), or any combination of two or more of these additives, including the combination of NAcMan and NAcGlc.
The present invention relates to a method of controlling quality and quantity of posttranslational modification of a recombinantly produced polypeptide/protein (glycoprotein), wherein the posttranslational modification affects the glycosylation profile and/or the acidic variants profile, as manifested in CEX profiles, wherein the polypeptide/protein (glycoprotein) production is in eukaryotic host cells, the method comprising the following steps: a) cultivating the eukaryotic cells in a suitable medium under conditions which allow the expression of the polypeptide/protein, wherein the content of the dissolved CO2 (pCO2) in the medium is at a first value during the initial growth phase of the eukaryotic cells, allowing the eukaryotic cells to grow, and b) increasing or decreasing the content of the dissolved CO2 (pCO2) in the medium during the production phase of the eukaryotic cells to a second value.
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
The invention relates to the preparation of chiral compounds, in particular to the preparation of chiral compounds which may be used as intermediates for the preparation of anti-diabetic agents, preferably sitagliptin.
C07C 67/343 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms
C07C 227/08 - Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
C07C 229/34 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
The present invention relates to a granulate and a pharmaceutical composition comprising fesoterodine or a salt or a solvate thereof and stabilizer, in particular to a pharmaceutical composition comprising fesoterodine or a salt or a solvate thereof and sucrose, polyethylene glycol, cyclodextrin, and combinations thereof and to a process for its preparation. The granulate and the pharmaceutical composition are particularly useful as a medicament, especially for the treatment of urinary incontinence. The present invention relates to use of sucrose, polyethylene glycol, cyclodextrin, and combinations thereof for stabilizing fesoterodine or a salt or a solvate thereof in a pharmaceutical composition.
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
86.
DRY FORMULATION AND PHARMACEUTICAL COMPOSITION COMPRISING FESOTERODINE OR A SALT OR A SOLVATE THEREOF
The present invention relates to a new pharmaceutical composition of fesoterodine or a salt or a solvate thereof, in particular to a dry formulation. The present invention relates to a new process for the preparation of dry formulation of fesoterodine or a salt or a solvate thereof. The pharmaceutical composition is particularly useful as a medicament, especially for the treatment of urinary incontinence.
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
The present invention relates to the field of chemical technology, more specifically to a novel and effective way of residual solvent removal comprising the application of ultrasonic treatment.
The process for the synthesis of statins featuring the use of an early intermediate (4R,6S)-6-(dialkoxymethyl)tetrahydro-2H-pyran-2,4-diol which already possesses the desired stereochemistry corresponding to the final statin.
The present invention discloses a process for preparing an active pharmaceutical ingredient (API) or intermediates thereof, notably particular step in the synthesis of an intermediate useful for example in the preparation of statins, by using an enzyme capable of catalyzing oxidation or dehydrogenation. The invention further provides an expression system effectively translating said enzyme. In addition, the invention relates to a specific use of such enzyme for preparing API or intermediate thereof, and in particular for preparing statin or intermediate thereof.
The present invention belongs to the field of pharmaceutical industry and relates to a process for preparing a pharmaceutical composition comprising a pharmaceutically active ingredient (API) that is poorly soluble in water, a pharmaceutical composition obtained according to said process, to a dosage form comprising said pharmaceutical composition and to the use of said dosage forms for the treatment of hypercholesterolemia.
The present invention relates to the field of organic chemistry, more specifically to the synthesis of intermediate compounds which can be used in the synthesis of pharmaceutically active agents such as anacetrapib or derivatives thereof.
The present invention relates to a method for selecting for cells or cell lines that produce a recombinant protein/polypeptide in high yields, the method allowing for the selection of high producer cells or cell lines in an early phase of cell line development, the method comprising the step of determining the nuclear DNA content of the cells or cell lines, wherein the level of the nuclear DNA content of the cells or cell lines positively correlates with the capacity of the cells or cell lines to produce the recombinant protein/polypeptide.
The present invention relates to a process for the preparation of 3-aroyl -5- aminobenzofuran derivatives useful as antiarrhythmic drugs which avoids the use of nitro intermediates.
A p ha rmaceutical composition comprises a combination of thiazolidinedione or a pharmaceutically acceptable salt thereof as a first pharmaceutically active ingredient and a second pharmaceutically active ingredient different from thiazolidinedione, wherein the amount of said second pharmaceutically ingredient is larger than that of the first pharmaceutically active ingredient, and wherein the combination of said first and second pharmaceutically active ingredients are provided by a first granulate comprising the first and second pharmaceutically active ingredients and optionally at least one excipient, said first granulate being present in a second granulate comprising a further pharmaceutical excipient.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
96.
PHARMACEUTICAL COMPOSITIONS COMPRISING GLIMEPIRIDE AND POLYETHYLENE GLYCOL CASTOR OIL
The present invention relates to the field of a pharmaceutical technology. More specifically, the present invention relates to a pharmaceutical composition comprising glimepiride and a surface active agent. Surface active agent obtainable by reacting castor oil or hydrogenated castor oil with ethylene oxide, preferably hydrogenated castor oil, substantially improves dissolution glimepiride active pharmaceutical ingredient and at the same time, when both formulated into a pharmaceutical composition, ensures satisfying or exceeding other parameters like for example stability, hardness, friability and handling of said pharmaceutical composition.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/64 - Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
The invention relates to commercially viable process for the synthesis of key intermediates for the preparation of statins, in particular Rosuvastatin and Pitavastatin or respective pharmaceutically acceptable salts thereof. A new simple and short synthetic route for key intermediates is presented which benefits from the use of cheap and readily available starting materials, by which the conventionally most frequently used DIBAL-H as reducing agent can be avoided.
The present invention describes new mammalian expression vectors comprising a novel combination of regulatory elements and one or more selection marker gene(s). The vector allows for incorporation of at least one, preferably two or more genes of interest, its/their subsequent expression, and for selection of transfected cells using, e.g., G418 and/or MTX. The pDGPΔGOI vector as an example for a mammalian expression vector according to the present invention exhibits a 9555 bp sequence, one strand of which is represented by SEQ ID NO:2.
The present application discloses a process for demethylating aromatic methyl ethers by reaction with 3 -mercaptopropionic acid or salts thereof. One preferred example is the demethylation of venlafaxine forming 0 - desmethylvenlafaxine.
C07B 41/02 - Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
C07C 213/08 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
C07C 215/64 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
C07C 45/67 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by isomerisationPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton
C07C 49/84 - Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
C07C 201/12 - Preparation of nitro compounds by reactions not involving the formation of nitro groups
C07C 205/25 - Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups bound to carbon atoms of six-membered aromatic rings being part of a condensed ring system
C07C 253/30 - Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
C07C 255/53 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and hydroxy groups bound to the carbon skeleton
100.
A NOVEL SYNTHETIC APPROACH TO ß-AMINOBUTYRYL SUBSTITUTED COMPOUNDS
The present invention relates to process to prepare β-aminobutyryl compounds of formula (I), wherein Q is N, CH, C-CF3 or C-phenyl, preferably N, and R10 is H, C1-C4-alkyl or fluorinated C1C2-alkyl, preferably trifluoromethyl, and wherein X is halogen selected from fluoro, chloro, or bromo, preferably fluoro, same or different, and n is 1-4.
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