335013-18-8Relevant articles and documents
Synthesis of a high specific activity methyl sulfone tritium isotopologue of fevipiprant (NVP-QAW039)
Luu, Van T.,Goujon, Jean-Yves,Meisterhans, Christian,Frommherz, Matthias,Bauer, Carsten
, p. 188 - 195 (2015)
The synthesis of a triple tritiated isotopologue of the CRTh2 antagonist NVP-QAW039 (fevipiprant) with a specific activity >3TBq/mmol is described. Key to the high specific activity is the methylation of a bench-stable dimeric disulfide precursor that is
ANTIMICROBIAL COMPOUNDS AND METHODS
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Paragraph 00599; 00600, (2020/07/31)
The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
ANTIMICROBIAL COMPOUNDS AND METHODS
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Paragraph 00392; 00393, (2020/07/31)
The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
NEW HETEROCYCLIC COMPOUNDS AS MONOACYLGLYCEROL LIPASE INHIBITORS
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Page/Page column 64; 237, (2020/03/05)
The invention provides new heterocyclic compounds having the general formula (I) wherein A, L, X, m, n, R1 and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds, methods of using the compounds and methods of determining the monoacylglycerol lipase (MAGL) inhibitory activity of the compounds.
NEW HETEROCYCLIC COMPOUNDS AS MONOACYLGLYCEROL LIPASE INHIBITORS
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Page/Page column 245, (2020/03/05)
The invention provides new heterocyclic compounds having the general formula (I) wherein A, L, X, m, n, R1 and R2 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
Design of N-Benzoxaborole Benzofuran GSK8175 - Optimization of Human Pharmacokinetics Inspired by Metabolites of a Failed Clinical HCV Inhibitor
Chong, Pek Y.,Shotwell, J. Brad,Miller, John,Price, Daniel J.,Maynard, Andy,Voitenleitner, Christian,Mathis, Amanda,Williams, Shawn,Pouliot, Jeffrey J.,Creech, Katrina,Wang, Feng,Fang, Jing,Zhang, Huichang,Tai, Vincent W.-F.,Turner, Elizabeth,Kahler, Kirsten M.,Crosby, Renae,Peat, Andrew J.
supporting information, p. 3254 - 3267 (2019/03/19)
We previously described the discovery of GSK5852 (1), a non-nucleoside polymerase (NS5B) inhibitor of hepatitis C virus (HCV), in which an N-benzyl boronic acid was essential for potent antiviral activity. Unfortunately, facile benzylic oxidation resulted in a short plasma half-life (5 h) in human volunteers, and a backup program was initiated to remove metabolic liabilities associated with 1. Herein, we describe second-generation NS5B inhibitors including GSK8175 (49), a sulfonamide-N-benzoxaborole analog with low in vivo clearance across preclinical species and broad-spectrum activity against HCV replicons. An X-ray structure of NS5B protein cocrystallized with 49 revealed unique protein-inhibitor interactions mediated by an extensive network of ordered water molecules and the first evidence of boronate complex formation within the binding pocket. In clinical studies, 49 displayed a 60-63 h half-life and a robust decrease in viral RNA levels in HCV-infected patients, thereby validating our hypothesis that reducing benzylic oxidation would improve human pharmacokinetics and lower efficacious doses relative to 1.
PYRAZOLE COMPOUNDS AS CRTH2 ANTAGONISTS
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Page/Page column 41, (2012/10/18)
The present invention relates to pyrazole compounds of formula (I) and pharmaceutically acceptable salts thereof having CRTH2 antagonistic activity, wherein L, Y1, Y2, Y3, Y4, Y5, Z, R1, R
SUBSTITUTED AMINOTHIAZOLONE INDAZOLES AS ESTROGEN RELATED RECEPTOR-ALPHA MODULATORS
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Page/Page column 154, (2011/06/28)
The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.
RENIN INHIBITORS
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Page/Page column 24, (2009/04/25)
The present invention relates to biphenyl compounds of formula (I). These compounds are renin inhibitors of a non- peptidic nature and of low molecular weight. The invention further relates to a pharmaceutical composition containing said compounds, as wel
QUINOXALINE DERIVATIVES AS INHIBITORS OF THE TYROSINE KINASE ACTIVITY OF JANUS KINASES
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Page/Page column 37, (2009/01/24)
The present invention relates to quinoxaline compound of the formula (I): wherein R1 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R7; R2 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R8; R3, R4, R5 and R6 are each independently hydrogen or R9; and R7, R8 and R9 are each independently selected from organic and inorganic substituents, their use in therapy of diseases, in particular diseases mediated by the tyrosine kinase activity of Janus kinases, including JAK-2 and JAK-3 kinases