- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
-
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
- -
-
Paragraph 001999; 002001
(2021/01/22)
-
- Liganding Functional Tyrosine Sites on Proteins Using Sulfur-Triazole Exchange Chemistry
-
Tuning reactivity of sulfur electrophiles is key for advancing click chemistry and chemical probe discovery. To date, activation of the sulfur electrophile for protein modification has been ascribed principally to stabilization of a fluoride leaving group (LG) in covalent reactions of sulfonyl fluorides and arylfluorosulfates. We recently introduced sulfur-triazole exchange (SuTEx) chemistry to demonstrate the triazole as an effective LG for activating nucleophilic substitution reactions on tyrosine sites of proteins. Here, we probed tunability of SuTEx for fragment-based ligand discovery by modifying the adduct group (AG) and LG with functional groups of differing electron-donating and -withdrawing properties. We discovered the sulfur electrophile is highly sensitive to the position of modification (AG versus LG), which enabled both coarse and fine adjustments in solution and proteome activity. We applied these reactivity principles to identify a large fraction of tyrosine sites (~30%) on proteins (~44%) that can be liganded across >1500 probe-modified sites quantified by chemical proteomics. Our proteomic studies identified noncatalytic tyrosine and phosphotyrosine sites that can be liganded by SuTEx fragments with site specificity in lysates and live cells to disrupt protein function. Collectively, we describe SuTEx as a versatile covalent chemistry with broad applications for chemical proteomics and protein ligand discovery.
- Brulet, Jeffrey W.,Borne, Adam L.,Yuan, Kun,Libby, Adam H.,Hsu, Ku-Lung
-
p. 8270 - 8280
(2020/05/25)
-
- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
-
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
- -
-
Paragraph 002041; 002042; 002044
(2019/07/17)
-
- NOVEL TRIAZOLONE DERIVATIVES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
-
The present technology provides triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).
- -
-
Paragraph 0195-0196
(2019/10/15)
-
- NOVEL ARYL OR HETEROARYL TRIAZOLONE DERIVATIVES OR SALTS THEREOF, OR PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
-
The present technology provides aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The aryl or heteroaryl triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).
- -
-
Paragraph 0227; 0230
(2019/10/15)
-
- MOLECULES HAVING CERTAIN PESTICIDAL UTILITIES, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES RELATED THERETO
-
This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules,
- -
-
Paragraph 0230; 0231
(2016/02/16)
-
- MOLECULES HAVING CERTAIN PESTICIDAL UTILITIES, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES RELATED THERETO
-
This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules,
- -
-
Paragraph 0172-0173
(2016/02/18)
-
- Discovery of Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor CC-223
-
We report here the synthesis and structure-activity relationship (SAR) of a novel series of mammalian target of rapamycin (mTOR) kinase inhibitors. A series of 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were optimized for in v
- Mortensen, Deborah S.,Perrin-Ninkovic, Sophie M.,Shevlin, Graziella,Zhao, Jingjing,Packard, Garrick,Bahmanyar, Sogole,Correa, Matthew,Elsner, Jan,Harris, Roy,Lee, Branden G. S.,Papa, Patrick,Parnes, Jason S.,Riggs, Jennifer R.,Sapienza, John,Tehrani, Lida,Whitefield, Brandon,Apuy, Julius,Bisonette, René R.,Gamez, James C.,Hickman, Matt,Khambatta, Godrej,Leisten, Jim,Peng, Sophie X.,Richardson, Samantha J.,Cathers, Brian E.,Canan, Stacie S.,Moghaddam, Mehran F.,Raymon, Heather K.,Worland, Peter,Narla, Rama Krishna,Fultz, Kimberly E.,Sankar, Sabita
-
p. 5323 - 5333
(2015/08/03)
-
- MOLECULES HAVING CERTAIN PESTICIDAL UTILITIES, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES RELATED THERETO
-
This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules,
- -
-
Paragraph 0378; 0379
(2014/09/29)
-
- SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS
-
Compounds of Formula I: and salts thereof in which R1, R2, R2a, R3, n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.
- -
-
Page/Page column 49
(2011/04/14)
-
- MTOR KINASE INHIBITORS FOR ONCOLOGY INDICATIONS AND DISEASES ASSOCIATED WITH THE MTOR/P13K/AKT PATHWAY
-
Provided herein are Heteroaryl Compounds having the following structure: R2 N (I) or (II) wherein R1 -R4 are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, neurodegenerative diseases, diabetes, obesity, neurological disorders, age-related diseases, or cardiovascular conditions, comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.
- -
-
Page/Page column 133
(2010/06/17)
-
- INHIBITORS OF JANUS KINASES
-
The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.
- -
-
Page/Page column 108-109
(2009/01/23)
-
- SUBSTITUENT AND COORDINATION EFFECTS IN SINGLET REACTIONS OF 3-DIAZO-3H-1,2,4-TRIAZOLES WITH SUBSTITUTED BENZENES AND NITRO COMPOUNDS
-
3-Diazo-3H-1,2,4-triazoles convert to singlet 3H-1,2,4-triazol-3-ylidenes which (1) effect directed electrophilic substitutions of benzenes and (2) coordinate with benzenoid substituents and nitro compounds to give decomposition or rearrangement products.
- Glinka, J.,Fiscus, D.,Rao, C. B.,Shechter, H.
-
p. 3221 - 3224
(2007/10/02)
-