- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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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.
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Paragraph 00567; 00569; 001389; 001390
(2021/01/22)
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- Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway
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Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.
- Němec, Václav,Hylsová, Michaela,Maier, Luká?,Flegel, Jana,Sievers, Sonja,Ziegler, Slava,Schr?der, Martin,Berger, Benedict-Tilman,Chaikuad, Apirat,Val?íková, Barbora,Uldrijan, Stjepan,Drápela, Stanislav,Sou?ek, Karel,Waldmann, Herbert,Knapp, Stefan,Paruch, Kamil
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p. 1062 - 1066
(2019/01/04)
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- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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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.
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Paragraph 00609; 00610; 00612; 001431; 001432; 001433
(2019/07/17)
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- IMIDAZO [1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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The invention provides substituted imidazo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidinyl carboxamide compounds described herein include substituted 2-heterocyclyl-4-alkyl-imidazo[1,5-a]pyrirnidine-8-carboxamide compounds and variants thereof.
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Paragraph 00218; 00296; 00597
(2017/11/04)
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- CONFORMATIONALLY CONSTRAINED CARBOXYLIC ACID DERIVATIVES USEFUL FOR TREATING METABOLIC DISORDERS
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The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I or the general formula III: where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.
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- AMINO NICOTINIC AND ISONICOTINIC ACID DERIVATIVES AS DHODH INHIBITORS
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A compound of formula (I) wherein : - one of the groups G1represents a nitrogen atom or a group CRc and the other represents a group CRc; - G2 represents a nitrogen atom or a group CRd; - R1 represents a group selected from hydrogen atoms, halogen atoms, C1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C3-8 cycloalkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - R2 represents a group selected from hydrogen atoms, halogen atoms, hydroxyl groups, C1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, C1-4 alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C3-8 cycloalkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - Ra, Rb and Rc independently represent groups selected from hydrogen atoms, halogen atoms, C1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C1-4alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - Rd represents a group selected from hydrogen atoms, halogen atoms, hydroxyl groups, C1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C1-4 alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C3-8 cycloalkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - one of the groups G3 and G4 is a nitrogen atom and the other is a CH group; - M is a hydrogen atom or an pharmaceutically acceptable cation with the proviso that, when at least one of the groups Ra and Rb represent a hydrogen atom and G2 is a group CRd, then Rd represents a groups selected from C1-4 alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, C3-8 cycloalkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; and the pharmaceutically acceptable salts and N-oxides thereof.
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Page/Page column 28
(2008/12/06)
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