Abstract: The disclosed embodiments detail improved methods for the synthesis of diketopiperazines from amino acids. In particular improved methods for the cyclocondensation and purification of N-protected 3,6-(aminoalkyl)-2,5-diketopiperazines from N-protected amino acids. Disclosed embodiments describe methods for the synthesis of 3,6-bis-[N-protected aminoalkyl]-2,5-diketopiperazine comprising heating a mixture of an amino acid in the presence of a catalyst in an organic solvent. The catalyst is selected from the group comprising sulfuric acid, phosphoric acid, p-toluenesulfonic acid, 1-propylphosphonic acid cyclic anhydride, tributyl phosphate, phenyl phosphonic acid and phosphorous pentoxide among others. The solvent is selected from the group comprising: dimethylacetamide, N-methyl-2-pyrrolidone, diglyme, ethyl glyme, proglyme, ethyldiglyme, m-cresol, p-cresol, o-cresol, xylenes, ethylene glycol and phenol among others.
Type:
Grant
Filed:
August 15, 2016
Date of Patent:
February 5, 2019
Assignee:
MannKind Corporation
Inventors:
John J. Freeman, Adrienne Stamper, Melissa Heitmann
Abstract: Provided herein are thiophene compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders, including but not limited to, psychosis and schizophrenia.
Type:
Grant
Filed:
February 8, 2013
Date of Patent:
January 29, 2019
Assignees:
SUNOVION PHARMACEUTICALS INC., PGI DRUG DISCOVERY LLC
Inventors:
John Emmerson Campbell, Una Campbell, Taleen G. Hanania, Liming Shao
Abstract: The present application relates to thienopyrrole derivatives, compounds of Formulas (I) and (Ia), wherein R, R1, R2 and R3 are as defined in the specification, pharmaceutical compositions containing such compounds and to their use in therapy. The compounds of the application can be useful for inhibiting KDM1 and the prevention and/or treatment of cancer, infectious disease, or a disease characterized by aberration of cellular energy metabolism, e.g., obesity.
Type:
Grant
Filed:
September 4, 2015
Date of Patent:
January 22, 2019
Assignee:
Istituto Europeo di Oncologia S.r.l.
Inventors:
Paola Vianello, Luca Sartori, Mario Varasi, Ciro Mercurio, Elisa Zagarri, Anna Cappa, Alessia Romussi, Manuela Villa, Giuseppe Meroni, Loris Moretti
Abstract: The present invention relates to crystalline forms of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide (Compound 1) and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor and are therefore useful in the treatment of CB2 receptor-mediated disorders, for example, osteoarthritis; pain; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation for example; atherosclerosis; undesired immune cell activity, and inflammation associated with a disorder selected from: osteoarthritis, anaphylaxis, Behcet's disease, graft rejection, vasculitis, gout, spondylitis, viral disease, bacterial disease, lupus, inflammatory bowel disease, autoimmune hepatitis, and type 1 diabetes mellitus; age-related macular degeneration; cough;
Type:
Grant
Filed:
August 26, 2016
Date of Patent:
January 22, 2019
Assignee:
Arena Pharmaceuticals, Inc.
Inventors:
Anthony C. Blackburn, Sangdon Han, Robert M. Jones, Antonio Garrido Montalban, Biman B. Pal, Jaimie Karyn Rueter
Abstract: A process for producing bis-anhydrohexitol ether compositions and in particular isohexide glycidyl ether compositions, one of the originalities of which is azeotropic distillation carried out under reduced pressure. Such compositions are used to produce epoxy resins, the function thereof being to form a three-dimensional macromolecular network. The compositions obtained according to the process are rich in diepoxy derivatives of isosorbide to the detriment of monoepoxy derivatives, only the first participating in the formation of the three-dimensional network. The crosslinking density is therefore increased, thereby making it possible to obtain a material which is more chemically resistant and mechanically stronger and which has a higher glass transition temperature (Tg), compared with the same materials obtained with bis-anhydrohexitol ether compositions according to the prior art.
Abstract: The present invention relates to canagliflozin Monohydrate and its crystalline forms, which as compared to the prior art, have higher stability in water or aqueous system, are more suitable for wet granulation processes or suspension preparations and have good storage stability; the present invention also relates to preparation methods of canagliflozin Monohydrate and its crystalline forms, pharmaceutical compositions thereof and uses thereof in preparation of drugs for treating diseases such as diabetes, diabetes complications, obesity and so on.
Abstract: A method of increasing the insulin sensitivity of a mammalian cell by contacting the cell with a protein phosphatase 2A (PP2A) inhibitor having the structure:
Abstract: Furfural is produced from biomass material containing pentosan, in high yields, in a production process comprising treating the biomass with a solution containing at least one ?-hydroxysulfonic acid thereby hydrolyzing the biomass to produce a product stream containing at least one C5-carbohydrate compound in monomeric and/or oligomeric form, and dehydrating the C5-carbohydrate compound in the presence of a heterogeneous solid acid catalyst, in a biphasic reaction medium comprising an aqueous phase and a water-immiscible organic phase, at a temperature in the range of from about 100° C. to about 250° C. to produce a dehydration product stream containing furfural. An aqueous stream is separated from the dehydration product, which can be optionally recycled to the hydrolysis step.
Type:
Grant
Filed:
August 13, 2015
Date of Patent:
November 27, 2018
Assignee:
SHELL OIL COMPANY
Inventors:
Juben Nemchand Chheda, Paul Richard Weider, Robert Lawrence Blackbourn, Jean Paul Andre Marie Joseph Ghislain Lange
Abstract: The present invention relates to an alkyd resin as well as to a method for preparing such a resin, said alkyd resin resulting from the polycondensation: of at least one polyacid, preferably biosourced, or its acid anhydride preferably biosourced, of at least one component based on oil, preferably biosourced, or its corresponding fatty acid, preferably biosourced, of at least one polyol, preferably biosourced, having at least two hydroxyl groups, selected from polyols comprising at least one 1,4:3,6-dianhydrohexitol unit, of rosin or of at least one of its derivatives, wherein at least one polyacid is succinic acid, preferably biosourced, or its anhydride, preferably biosourced; and wherein the percentage by dry weight of rosin or its derivatives based on the total dry weight of succinic acid and of its anhydride and of rosin or its derivatives is comprised between about 10% and about 80%.
Type:
Grant
Filed:
August 5, 2014
Date of Patent:
November 20, 2018
Assignees:
A Et A Mader, Roquette Freres
Inventors:
Cyril Barquant, Joël Roussel, Clothilde Buffe, Laura Crowther-Alwyn
Abstract: The present invention relates to fungicidal N-cycloalkyl-N-[(heterocyclylphenyl)methylene] carboxamide derivatives and their thiocarbonyl derivatives, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions.
Type:
Grant
Filed:
April 18, 2013
Date of Patent:
November 13, 2018
Assignee:
BAYER CROPSCIENCE AG
Inventors:
Christoph Braun, Pierre Cristau, Peter Dahmen, Philippe Desbordes, Mazen Es-Sayed, Helene Lachaise, Philippe Rinolfi, Jan-Peter Schmidt, Tomoki Tsuchyia, Jean-Pierre Vors, Ulrike Wachendorff-Neumann
Abstract: The present invention relates to deuterated 1-piperazino-3-phenyl-indanes and salts thereof with activity at dopamine receptors D1 and D2 as well as the 5HT2 receptors in the central nervous system, to medicaments comprising such compounds as active ingredients, to the use of such compounds in the treatment of diseases in the central nervous system, and to methods of treatment comprising administration of such compounds.
Type:
Grant
Filed:
February 17, 2017
Date of Patent:
November 6, 2018
Assignee:
H. LUNDBECK A/S
Inventors:
Morten Jorgensen, Peter Hongaard Andersen, Klaus Gjervig Jensen
Abstract: The invention provides crystalline (2S)-3-[(3S,4S)-3-[(1R)-1-hydroxyethyl]-4-(4-methoxy-3-{[1-(5-methylpyridin-2-yl)azetidin-3-yl]oxy}phenyl)-3-methylpyrrolidin-1-yl]-3-oxopropane-1,2-diol, and pharmaceutical compositions thereof. The invention further provides methods of using this compound to treat overactive bladder.
Abstract: Isoandrographolide-19-propionate for treatment of non-alcoholic fatty liver disease (NALFD) relates to the compound isoandrographolide-19-propionate (IAN-19P), having the structural formula: and pharmaceutically acceptable salts thereof. The compound is synthesized by reaction of isoandrographolide with anhydrous propionic acid in the presence of N,N?-dicyclohexylcarbodiimide and 4-dimethylaminopyridine. In vitro testing shows that isoandrographolide-19-propionate has lower toxicity than andrographolide, but has significantly high activity at a concentration of 50 ?M. IAN-19P produced normal triglyceride levels and significantly lowered lipoperoxide formation in palmitate-oleate induced steatotic HepG2 cells, and also lowered ALT leakage from the treated cells.
Type:
Grant
Filed:
January 8, 2018
Date of Patent:
September 4, 2018
Assignee:
KING SAUD UNIVERSITY
Inventors:
Naif Abdullah Al-Dhabi, Savarimuthu Ignacimuthu, P. Pandikumar, Erenius Toppo, Sylvester Darvin
Abstract: A new class of ligands derived from benzo[h]quinoline are described and these ligands are used to prepare several novel transition metal complexes. The complexes are preferably of the group VIII transition metals iron, ruthenium or osmium, with the benzo[h]quinolone ligands acting as tridentate ligands. The complexes described are proved to be very active catalysts for the reduction of ketones and aldehydes to alcohols, via hydrogen transfer and hydrogenation reactions. These compounds hence can be usefully employed as catalysts in said reduction reactions.
Type:
Grant
Filed:
March 16, 2016
Date of Patent:
July 3, 2018
Assignee:
UNIVERSITA' DEGLI STUDI DI UDINE
Inventors:
Pierluigi Rigo, Walter Baratta, Katia Siega, Giorgio Adolfo Chelucci, Maurizio Ballico, Santo Magnolia
Abstract: Compounds and compositions comprising compounds that inhibit glutaminase are described herein. Also described herein are methods of using the compounds that inhibit glutaminase in the treatment of cancer.
Type:
Grant
Filed:
November 21, 2013
Date of Patent:
July 3, 2018
Assignee:
Agios Pharmaceuticals, Inc.
Inventors:
Rene M. Lemieux, Janeta Popovici-Muller, Francesco G. Salituro, Jeffrey O. Saunders, Jeremy Travins, Shunqi Yan
Abstract: The invention provides simple small molecule, non-heme iron catalyst systems with broad substrate scope that can predictably enhance or overturn a substrate's inherent reactivity preference for sp3-hybridized C—H bond oxidation. The invention also provides methods for selective aliphatic C—H bond oxidation. Furthermore, a structure-based catalyst reactivity model is disclosed that quantitatively correlates the innate physical properties of the substrate to the site-selectivities observed as a function of the catalyst. The catalyst systems can be used in combination with oxidants such as hydrogen peroxide to effect highly selective oxidations of unactivated sp3 C—H bonds over a broad range of substrates.
Type:
Grant
Filed:
September 9, 2014
Date of Patent:
March 27, 2018
Assignee:
The Board of Trustees of the University of Illinois
Abstract: Malonic ester derivatives of the formula (I) in which the symbols A1, A2, Y, R10, p, X, R2, G, Q, L2 and R1 are each as defined in the description, and salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).
Type:
Grant
Filed:
August 26, 2014
Date of Patent:
March 27, 2018
Assignee:
BAYER CROPSCIENCE AKTIENGESELLSCHAFT
Inventors:
Stefan Hillebrand, Matthias Riedrich, Sebastian Hoffmann, Mark James Ford, Joachim Telser, Mazen Es-Sayed, Guenter Hoemberger, Pierre Wasnaire, Ulrike Wachendorff-Neumann, Tomoki Tsuchiya, Valerie Toquin
Abstract: The invention relates to a method for producing a hydrazine of general formula (I) and the pharmaceutically acceptable salts thereof from an amine of formula (II), characterised in that said method uses a urea of formula (III) as a synthesis intermediate.
Type:
Grant
Filed:
December 27, 2013
Date of Patent:
March 6, 2018
Assignee:
AVIRAGEN THERAPEUTICS, INC.
Inventors:
Marta Blumenfeld, Delphine Compere, Marco A. Ciufolini
Abstract: A composition and method are disclosed for capturing CO2. A pollutant/greenhouse gas can be converted into a valuable organic compound using a nontoxic reducing agent. CO2 may be economically captured from the atmosphere, from products of combustion, or from byproducts of various chemical processes. The method reduces CO2 in a three-step reaction cycle, in which a binuclear metal-organic compound converts CO2 to oxalate in a redox cycle under mild conditions.
Type:
Grant
Filed:
October 13, 2014
Date of Patent:
February 27, 2018
Inventors:
Andrew W. Maverick, Uttam R. Pokharel, Frank R. Fronczek
Abstract: The present invention relates to a process for the preparation of Compound (A): wherein the process comprises contacting atazanavir base (Compound (II)) with sulphuric acid in a combination of two or more solvents and isolating compound (A). The present invention also relates to substantially pure Compound (A), and to Compound (A) devoid of mesityl oxide impurity.
Type:
Grant
Filed:
February 12, 2014
Date of Patent:
February 13, 2018
Assignee:
Cipla Limited
Inventors:
Rajendra Narayanrao Kankan, Srinivas Laxminarayan Pathi, Venugopalarao Chinimilli