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NOVEL TETRAHYDRO-1H-PYRIDO [4,3-b] INDOLE DERIVATIVES AS CB1? RECEPTOR LIGANDS

Compounds of Formulae I, or pharmaceutically acceptable salts thereof: wherein R1, R2 and R3 are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Metabolomics and the diagnosis of human diseases-a guide to the markers and pathophysiological pathways affected

This review was designed as a handbook of metabolomic markers of high significance for a wide range of human diseases. This is the first report to collate results from recent studies in a format that allows ready identification of key metabolites by cross-comparisons of results from one disease to another. All the data presented in this work were obtained by previous research carried out exclusively during clinical trials in humans. Also, discussion of the pathophysiological pathways linked to the markers described is provided. The clinical assays focused on non-targeted or targeted metabolomics and metabolite profiling (focused assays which only refer to a limited array of known biomarkers, applying discriminatory and bioinformatic tools to them) as well as predictive modelling based on clinical trials. The data also highlight pathways and biological compounds that are disrupted at early stages of the diseases, in order to help elucidate target compounds and the pathophysiology of the considered diseases for early prognosis and diagnosis using noninvasive samples (saliva, sputum, serum, plasma, blood, urine, tissue, faecal water or faeces). In the tables, the candidate metabolites for biomarkers of diagnosis, or the biomarkers themselves, are detailed, indicating the type of sample in which they were detected and their up-or down-regulation (if calculated). The metabolites derived from each study have been filtered carefully, according to the analytical platform, and biostatistical discriminant analyses developed. Among the pool of data provided, those reaching a level of significance of p=0.05-0.0001, according to the Bonferroni correction, Steel-Dwass t-or Wilcoxon matched pair tests, are shown.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones and 1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-ones as PDE1 Inhibitors

The present invention provides 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones and 1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-ones of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Deacylative transformations of ketones via aromatization-promoted C?C bond activation

Carbon?hydrogen (C?H) and carbon?carbon (C?C) bonds are the main constituents of organic matter. Recent advances in C?H functionalization technology have vastly expanded our toolbox for organic synthesis1. By contrast, C?C activation methods that enable editing of the molecular skeleton remain limited2?7. Several methods have been proposed for catalytic C?C activation, particularly with ketone substrates, that are typically promoted by using either ring-strain release as a thermodynamic driving force4,6 or directing groups5,7 to control the reaction outcome. Although effective, these strategies require substrates that contain highly strained ketones or a preinstalled directing group, or are limited to more specialist substrate classes5. Here we report a general C?C activation mode driven by aromatization of a pre-aromatic intermediate formed in situ. This reaction is suitable for various ketone substrates, is catalysed by an iridium/phosphine combination and is promoted by a hydrazine reagent and 1,3-dienes. Specifically, the acyl group is removed from the ketone and transformed to a pyrazole, and the resulting alkyl fragment undergoes various transformations. These include the deacetylation of methyl ketones, carbenoid-free formal homologation of aliphatic linear ketones and deconstructive pyrazole synthesis from cyclic ketones. Given that ketones are prevalent in feedstock chemicals, natural products and pharmaceuticals, these transformations could offer strategic bond disconnections in the synthesis of complex bioactive molecules.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION

The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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TRICYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS

The present invention relates to Tricyclic Heterocycle Compounds of Formula (I): (I) and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, R3, R4, R5, R6 and n are as defined herein. The present invention also relates to compositions comprising at least one Tricyclic Heterocycle Compound, and methods of using the Tricyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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BENZOFURO[3,2-c] PYRIDINES AND RELATED ANALOGS AS SEROTONIN SUB-TYPE 6 (5-HT6) MODULATORS FOR THE TREATMENT OF OBESITY, METABOLIC SYNDROME, COGNITION AND SCHIZOPHRENIA

The present invention relates to benzofuro[3,2-c]pyridine and azepine analogs as serotonin sub-type 6 (5-HT6) modulators, pharmaceutical compositions including these compounds, methods of preparation, and use thereof. These compounds are useful in the treatment of central nervous system disorders including obesity, metabolic syndrome, cognition, schizophrenia, attention deficit hyperactivity disorder, bipolar disorder, rare and orphan diseases, and sleep disorders. The subject compounds have the structure of formula (I) with the substituents being described herein.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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BIARYLMETHYL HETEROCYCLES

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are biased agonists, or beta-Arrestin agonists of the angiotensin II receptor, which may be used as medicaments.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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COMPOUNDS

Provided are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for example Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem