Abstract: Provided herein are methods for evaluating the effect of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide or a pharmaceutically acceptable stereoisomer, tautomer, solid form, polymorph, salt, hydrate, clathrate, or solvate thereof in a patient with an assay based on UVB-irradiation and phosphorylated c-Jun expression. The analyses allow for evaluation of dose-response and identification of patient populations who are sensitive to 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide or a pharmaceutically acceptable stereoisomer, tautomer, solid form, polymorph, salt, hydrate, clathrate, or solvate thereof.
Abstract: Provided herein are methods for treating or preventing glioblastoma multiforme (GBM) characterized by O6-methylguanine-DNA methyltransferase (MGMT) expression and/or promoter methylation status, comprising administering an effective amount of a Dihydropyrazino-Pyrazine Compound to a patient having glioblastoma multiforme (GBM) characterized by O6-methylguanine-DNA methyltransferase (MGMT) expression and/or promoter methylation status.
Abstract: Provided herein are methods for the preparation of substituted pyrazino[2,3-b]pyrazines of the formula (II): the method comprising contacting a compound of formula (VI): with R1—Y in a solvent, in the presence of a palladium catalyst, wherein said contacting occurs in the presence of a base, wherein R1-R3, Y, the palladium catalyst and the base are as defined herein.
Type:
Grant
Filed:
August 18, 2017
Date of Patent:
January 1, 2019
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Jan Elsner, Roy L. Harris, Branden Gingsee Lee, Deborah Mortensen, Garrick K. Packard, Patrick Papa, Jason Parnes, Sophie Perrin-Ninkovic, Jennifer Riggs, John Sapienza, Graziella I. Shevlin, Lida Tehrani, Jingjing Zhao
Abstract: Provided herein are Aminopurine Compounds having the following structures: wherein R1, R2, and R3 are as defined herein, compositions comprising an effective amount of an Aminopurine Compound, and methods for treating or preventing a cancer, for example, melanoma.
Type:
Grant
Filed:
July 5, 2017
Date of Patent:
December 11, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Matthew Alexander, Joshua Hansen, Dehua Huang, Robert Hubbard, Raj K. Raheja, Kimberly Schwarz, Marianne Sloss, Eduardo Torres, JingJing Zhao
Abstract: Provided are pharmaceutical compositions and dosage forms of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, or a pharmaceutically acceptable stereoisomer, tautomer, solid form, polymorph, salt, hydrate, clathrate, or solvate thereof. Also provided are methods of treating, managing, or preventing various disorders, such as diseases or disorders treatable or preventable by inhibition of a JNK pathway in mammals using such pharmaceutical compositions or dosage forms. Further provided are salts of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide and methods of preparation of such salts.
Type:
Grant
Filed:
September 18, 2017
Date of Patent:
November 20, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Nathan Andrew Boersen, Indrajit Ghosh, Lianfeng Huang, Daozhong Zou
Abstract: Provided herein are compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, solid forms, isotopologues and metabolites thereof, and methods of their use for the treatment of a disease, disorder, or condition.
Abstract: Provided herein are formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one.
Type:
Grant
Filed:
October 23, 2017
Date of Patent:
August 21, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Anil Menon, Darshan K. Parikh, Dora Visky, Nathan Boersen, Thomas Lee, Xiaozhang Liang
Abstract: Provided herein are formulations, solid forms and methods of use relating to (1s,4s)-4-(2-(((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)amino)-8-((2,4,6-trichlorophenyl)amino)-9H-purin-9-yl)-1-methylcyclohexane-1-carboxamide.
Type:
Grant
Filed:
March 31, 2017
Date of Patent:
August 14, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Zheng Chen, Paul F. Fernandez, Tracy L. Gaebele, Lianfeng Huang, Matthew J. Jackson, Matthew M. Kreilein, Xiaoling Lu, Wenju Wu, Jean Xu
Abstract: Provided herein are Diaminopyrimidine Compounds having the following structures: wherein R1, R2, R3, and R4 are as defined herein, compositions comprising an effective amount of a Diaminopyrimidine Compound, and methods for treating or preventing liver fibrotic disorders or a condition treatable or preventable by inhibition of a JNK pathway.
Type:
Grant
Filed:
June 7, 2017
Date of Patent:
August 7, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Mercedes Delgado, Jan Elsner, Paul Erdman, Robert Hilgraf, Laurie Ann LeBrun, Meg McCarrick, Mark A. Nagy, Stephen Norris, David A. Paisner, Yoshitaka Satoh, Marianne Sloss, Jayashree Tikhe, Won Hyung Yoon
Abstract: Provided herein are methods for treating or preventing a cancer, comprising administering an effective amount of a TOR kinase inhibitor and an effective amount a second active agent to a patient having a cancer.
Type:
Grant
Filed:
July 20, 2017
Date of Patent:
June 26, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Kimberly Elizabeth Fultz, Tam Minh Tran, Shuichan Xu, Weiming Xu
Abstract: Provided herein are formulations, processes, solid forms and methods of use relating to the Compound for formula 1: having the name 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and tautomers thereof.
Abstract: Provided herein are methods for treating or preventing chronic lymphocytic leukemia, comprising administering an effective amount of a Dihydropyrazino-Pyrazine Compound to a patient having chronic lymphocytic leukemia.
Type:
Grant
Filed:
October 21, 2016
Date of Patent:
May 29, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Heather Raymon, Shuichan Xu, Antonia Lopez-Girona, Toshiya Tsuji, Kristen Mae Hege
Abstract: Provided herein are formulations, processes, solid forms and methods of use relating to the compound of formula (I): having the name 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and tautomers thereof.
Abstract: Provided herein are compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, solid forms, isotopologs and metabolites thereof, and methods of their use for the treatment of a disease, disorder, or condition.
Type:
Grant
Filed:
September 19, 2017
Date of Patent:
May 22, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Marie Georges Beauchamps, Antonio Christian Ferretti, Juan Antonio Gamboa, Kevin Klopfer, William Edward Konnecke, Matthew Michael Kreilein, Anil Menon, Amanda Nicole Miklos, John Fitzgerald Traverse
Abstract: Provided herein are methods for treating or preventing a solid tumor, non-Hodgkin lymphoma or multiple myeloma in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having a solid tumor, non-Hodgkin lymphoma or multiple myeloma.
Type:
Grant
Filed:
September 27, 2016
Date of Patent:
April 10, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Shuichan Xu, Kristen Mae Hege, Antonia Lopez-Girona, Heather Raymon, Rama K. Narla, Rajesh Chopra
Abstract: Provided herein are methods for treating or preventing a cancer, comprising administering an effective amount of a Dihydropyrazino-Pyrazine Compound and an effective amount of an androgen receptor antagonist to a patient having a cancer.
Type:
Grant
Filed:
April 16, 2014
Date of Patent:
April 10, 2018
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Heather Raymon, Toshiya Tsuji, Rama K. Narla, Kristen Mae Hege
Abstract: Provided herein are formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one.
Type:
Grant
Filed:
May 10, 2016
Date of Patent:
November 28, 2017
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Matthew Michael Kreilein, Thomas Lee, Ying Li, Jean Xu, William Wei-Hwa Leong, Benjamin Cohen
Abstract: Provided herein are formulations, processes, solid forms and methods of use relating to 2 -(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide.
Type:
Grant
Filed:
May 12, 2016
Date of Patent:
November 14, 2017
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Hon-Wah Man, Jean Xu, Marie Georges Beauchamps, Mohit Atul Kothare, Nanfei Zou, Ying Li, Lianfeng Huang, Daozhong Zou
Abstract: Provided are pharmaceutical compositions and dosage forms of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, or a pharmaceutically acceptable stereoisomer, tautomer, solid form, polymorph, salt, hydrate, clathrate, or solvate thereof. Also provided are methods of treating, managing, or preventing various disorders, such as diseases or disorders treatable or preventable by inhibition of a JNK pathway in mammals using such pharmaceutical compositions or dosage forms. Further provided are salts of 2-(tert-butylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide and methods of preparation of such salts.
Type:
Grant
Filed:
December 15, 2015
Date of Patent:
October 24, 2017
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Nathan Andrew Boersen, Indrajit Ghosh, Lianfeng Huang, Daozhong Zou
Abstract: Provided herein are compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, solid forms, isotopologues and metabolites thereof, and methods of their use for the treatment of a disease, disorder, or condition.
Type:
Grant
Filed:
February 8, 2017
Date of Patent:
October 24, 2017
Assignee:
Signal Pharmaceuticals, LLC
Inventors:
Marie Georges Beauchamps, Antonio Christian Ferretti, Juan Antonio Gamboa, Kevin Klopfer, William Edward Konnecke, Matthew Michael Kreilein, Anil Menon, Amanda Nicole Miklos, John Fitzgerald Traverse