Abstract: A pyridinylmethylenepiperidine derivatives and uses thereof, specifically, the present invention relates to a novel pyridinylmethylenepiperidine compound and a pharmaceutical composition containing this compound, which may be used for activating 5-HT1F receptor. The present invention also relates to methods of preparing this compound and pharmaceutical composition, and their use in the manufacture of a medicament for treating a 5-HT1F receptor-related disease, especially migraine.
Abstract: A full continuous-flow preparation method of vitamin B1 includes: (S1) feeding 3-chloro-4-oxopentyl acetate, 2-methyl-4-amino-5-(aminomethyl) pyrimidine and carbon disulfide to a first continuous-flow reactor for addition; (S2) allowing the reaction mixture to flow into a first continuous filtration and reaction device to collect a filter cake; subjecting the filter cake and hydrochloric acid solution to cyclization; transporting the reaction mixture and an aqueous inorganic base solution to a micromixer and a second continuous-flow reactor for hydrolysis to obtain thiothiamine; (S3) transporting the thiothiamine to a third continuous-flow reactor with hydrogen peroxide for oxidation to obtain thiamine sulfate; and (S4) allowing the thiamine sulfate to enter a second continuous filtration and reaction device for filtration to collect a filter cake; and subjecting the filter cake to reaction with organic hydrochloric acid solution followed by filtration and drying to obtain vitamin B1.
Abstract: The present invention relates to salts and crystalline forms of 2-(3-(8-Amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-4-methylphenyl)-3,3,3-trifluoro-2-hydroxypropanamide, crystalline forms of 8-amino-N-(2-hydroxy-2-methylpropyl)-3-(2-methyl-5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)imidazo[1,2-a]pyrazine-6-carboxamide, and crystalline forms of 8-amino-N-(2-hydroxy-2-methylpropyl)-3-(2-(methyl-d3)-5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)imidazo[1,2-a]pyrazine-6-carboxamide, which are PI3K inhibitors useful in the treatment of cancer and other diseases.
Type:
Grant
Filed:
September 4, 2019
Date of Patent:
November 30, 2021
Assignee:
Incyte Corporation
Inventors:
Brent Douty, David M. Burns, Andrew P. Combs, Zhongjiang Jia, Daniel Levy, Eddy W. Yue
Abstract: Adrenergic receptor modulating compounds and methods of using the same are provided. Also provided are methods of treating a subject for a disease or condition associated with an adrenergic receptor including administering a therapeutically effective amount of the subject compound. Aspects of the disclosure include a method of modulating an inflammatory pathway in a cell, such as the production of TNF-alpha in the cell. The method can include contacting a cell with ?1-selective adrenergic receptor modulating compound to selectively activate a cAMP pathway over a beta-arrestin pathway in the cell. Pharmaceutical compositions and kits which include the subject compounds are provided.
Type:
Grant
Filed:
May 12, 2017
Date of Patent:
November 16, 2021
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
Mehrdad Shamloo, Alam Jahangir, Bitna Yi, Andrew Kelley Evans, Michael John Green
Abstract: Disclosed are benzimidazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein R1, R2, R3, R4, Y and X are as described herein. In certain embodiments, a compound disclosed herein activates AMPK, and can be used to treat disease by activating the AMPK pathway.
Type:
Grant
Filed:
August 15, 2017
Date of Patent:
November 16, 2021
Assignee:
Rigel Pharmaceuticals, Inc.
Inventors:
Simon Shaw, Xiang Xu, Sarkiz Issakani, Rajinder Singh, Yasumichi Hitoshi, Matthew Duncton, Nan Lin
Abstract: The present disclosure relates to crystalline particles of N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I) having specific surface area (SSA) in the range from about 8 to about 16 m2/g, preferably from about 10 to about 15 m2/g, and to the method for the preparation of such particles. Compound (I) is a potent androgen receptor (AR) modulator which is useful as a medicament for example in the treatment of prostate cancer.
Abstract: The invention provides a compound of formula 1 or a pharmaceutically-acceptable salt thereof, that is useful as a JAK inhibitor. The invention also provides crystalline forms of the compound, pharmaceutical compositions comprising the compound, methods of using the compound to treat diseases amenable to a JAK inhibitor, and processes and intermediates useful for preparing the compound.
Type:
Grant
Filed:
October 18, 2019
Date of Patent:
November 2, 2021
Assignee:
Theravance Biopharma R&D IP, LLC
Inventors:
Robert Murray McKinnell, Venkat R. Thalladi, Hao Zhang, Paul R. Fatheree, Lan Jiang, Marta Dabros, Jerry Nzerem
Abstract: The invention provides a compound for use in the treatment of T-Cell Acute Lymphoblastic Leukaemia (T-ALL), the compound having the formula (1): or being a pharmaceutically acceptable salt thereof; wherein: n is 0, 1 or 2; Ar1 is selected from an optionally substituted phenyl, pyridyl, thienyl and furanyl; Q1 is selected from C(?O), S(?O) and SO2; A is absent or is NR2; R1 is selected from: hydrogen; an optionally substituted C1-6 non-aromatic hydrocarbon group; and optionally substituted 3- to 7-membered non-aromatic carbocyclic and heterocyclic rings containing one or two heteroatom ring members selected from O, N and S, and bridged bicyclic heterocyclic rings of seven to nine ring members of which one or two are nitrogen atoms, the carbocyclic and heterocyclic rings and bridged bicyclic heterocyclic rings; R2 is selected from hydrogen and C1-4 alkyl; or NR1R2 forms an optionally substituted 4- to 7-membered non-aromatic nitrogen-containing heterocyclic ring optionally containing a second hete
Abstract: The present invention provides methods for treating a cancer in a subject and for inhibiting tumor growth, metastasis or a dihydrorotate oxygenase enzyme activity of a tumor or cancer cell. At least one trisubstituted benzotriazole derivative with the formula (I) is administered to the subject or is contacted with the cancer cell. Compounds of formula (I) have substituents R1, R2 and R3 which have the meanings given in the specification, and pharmaceutically acceptable salts thereof.
Abstract: Disclosed are compounds of Formula (I) and (Ia): or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R4, R5, R6, and R7 are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.
Type:
Grant
Filed:
March 19, 2019
Date of Patent:
October 19, 2021
Assignee:
Plexxikon Inc.
Inventors:
Jiazhong Zhang, Hannah Powers, Aaron Albers, Phuongly Pham, Guoxian Wu, John Buell, Wayne Spevak, Zuojun Guo, Jack Walleshauser, Ying Zhang
Abstract: Disclosed are substituted heterocycle compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.
Type:
Grant
Filed:
August 31, 2018
Date of Patent:
October 12, 2021
Assignee:
Northwestern University
Inventors:
Gary E. Schiltz, Rama K. Mishra, Huiying Han, Sarki A. Abdulkadir, Javier Izquierdo-Ferrer, Atul D. Jain
Abstract: A zirconium metal-organic framework, which is a coordination product formed between zirconium ion clusters and a linker that links together adjacent zirconium ion clusters, wherein the linker is of formula (I) wherein R1 to R4 are independently hydrogen, an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted arylalkyl, an optionally substituted alkoxy, a hydroxyl, a carboxyl, a halo, a nitro, or a cyano, R5 is hydrogen, an optionally substituted alkyl, an optionally substituted alkoxy, an amino, a hydroxyl, a carboxyl, a halo, a nitro, or a cyano, and R6 and R7 are independently a hydrogen or an optionally substituted alkyl group having 1 to 4 carbon atoms. A method of detecting copper cations and/or chromate anions in a fluid sample with zirconium metal-organic framework.
Type:
Grant
Filed:
October 22, 2019
Date of Patent:
September 21, 2021
Assignee:
KING FAHD UNIVERSITY OF PETROLEUM AND MINERALS
Abstract: 12(S)-hydroxyeicosatrienoic acid (12(S)-HETrE) compounds and compositions comprising the same are disclosed. Methods of using the compounds in the prevention and treatment of thrombosis and thrombotic disorders are also disclosed.
Type:
Grant
Filed:
June 23, 2017
Date of Patent:
September 7, 2021
Assignees:
THE REGENTS OF THE UNIVERSITY OF MICHIGAN, THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Inventors:
Michael Holinstat, Theodore R. Holman, Andrew White
Abstract: The compound 2-(4-tert-Butylphenyl)-1H-benzo[d]imidazol-5-ol: and its use are disclosed. The compound activates Ppargc1a and, as a consequence, is useful for treating neuroinflammation and for treating a variety of neurodegenerative diseases.
Type:
Grant
Filed:
October 13, 2020
Date of Patent:
September 7, 2021
Assignee:
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Inventors:
Samuel D. Banister, Edgar Engleman, Khoa D. Nguyen, Mark Smith
Abstract: The present invention provides novel derivative of ?-lactam antibiotics, such as meropenem. The inventive compounds include compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are particles (e.g., nanoparticles) and pharmaceutical compositions thereof that are mucus penetrating. The inventive particles and pharmaceutical compositions may be useful in delivering an inventive compound to the respiratory tract of a subject. The invention further provides methods of using and kits including the inventive compounds, particles thereof, and/or pharmaceutical compositions thereof for treating and/or preventing a pulmonary disease (e.g., a respiratory tract infection).
Type:
Grant
Filed:
July 11, 2019
Date of Patent:
August 17, 2021
Assignee:
Kala Pharmaceuticals, Inc.
Inventors:
Winston Zapanta Ong, Pawel Wojciech Nowak, Jinsoo Kim, Elizabeth M. Enlow, James Bourassa, Yen Cu, Alexey Popov, Hongming Chen
Abstract: Disclosed herein, inter alia, compounds and methods of use thereof for the modulation of USP7 activity.
Type:
Grant
Filed:
September 20, 2019
Date of Patent:
August 10, 2021
Assignee:
RAPT THERAPEUTICS, INC.
Inventors:
Berenger Biannic, Xinping Han, Dennis X. Hu, Paul Robert Leger, Jack Maung, Akinori Okano, Jacob Bradley Schwarz, David Juergen Wustrow, Kyle Young, Gene Cutler, Yamini Ohol-Gupta
Abstract: The disclosed subject matter provides methods of using nitroxyl donating compounds and pharmaceutical compositions comprising such compounds in a dose escalation regimen.
Type:
Grant
Filed:
January 2, 2018
Date of Patent:
August 10, 2021
Assignee:
Bristol-Myers Squibb Company
Inventors:
Paul D. Kessler, William R. Ewing, Maria Borentain, Tushar Garimella, Elyse G. Stock
Abstract: The invention provides modulators of indoleamine 2,3-dioxygenase (IDO1) and their use in the prophylaxis and/or treatment of IDO1-mediated diseases. Specifically, the present invention provides compounds according to Formula (I) an enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof.
Type:
Grant
Filed:
November 3, 2017
Date of Patent:
August 3, 2021
Assignee:
Phenex Discovery Verwaltungs-GmbH
Inventors:
Christoph Steeneck, Olaf Kinzel, Simon Anderhub, Martin Hornberger, Gerald Kleymann, Thomas Hoffmann
Abstract: Disclosed in the present invention is an aminopyrimidine five-membered heterocyclic compound, and an intermediate, preparation method, pharmaceutical composition and application thereof. The aminopyrimidine five-membered heterocyclic compound provided by the present invention has a significant antagonistic effect on adenosine A2A receptors, and may be used as an antagonist for adenosine A2A receptors to effectively relieve or treat immune tolerance, diseases of the central nervous system, inflammatory diseases and like related diseases, while the preparation method is simple.
Abstract: The present disclosure provides a compound of Formula (I?): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein R1, R2, Rx, X1, n, n1, and q are as defined herein, and methods of making and using same.
Type:
Grant
Filed:
March 31, 2020
Date of Patent:
July 6, 2021
Inventors:
Rohan Eric John Beckwith, Simone Bonazzi, Artiom Cernijenko, Aleem Fazal, Ritesh Bhanudasji Tichkule, Michael Scott Visser