- INDOLE AMIDE DERIVATIVES AND RELATED COMPOUNDS FOR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
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This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.
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- Thrombin inhibitors
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Novel five-membered heterocyclic amidines, their preparation and use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. Pharmaceutical compositions which contain the compounds as active ingredients, and use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents.
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Page column 34
(2010/02/06)
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- Synthesis of 4-Hydroxy-N--2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-Dioxide and oxoacetic Acid. Major Metabolites of Isoxicam
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4-Hydroxy-N--2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (2), the major oxidative human metabolite of isoxicam (1), and oxoacetic acid (3), the major rat metabolite of isoxicam (1), were synthesized. 2 was synthesized by condensation of the known benzothiazine ester 8 with the isoxazolamine 9b. 9b was synthesized via a nine-step sequence starting with 5-methyl-3-isoxazolecarboxylic acid (14).NBS bromination of 14 gave 5-(bromomethyl)-3-isoxazolecarboxylic acid, which was coverted to the carbamate ester via a Curtius rearrangement of the acid azide.Displacement of bromine with silver acetate gave the acetoxy compound 21.Hydrolysis of 21 gave the unstable 3-isoxazolamine derivative 9a, which was converted to the OSiMe3 derivative 9b.The compound 3 was synthesized by reaction of ethyl oxalyl chloride with 5-methyl-3-isoxazolamine followed by base hydrolysis.
- Sircar, Jagadish C.,Capiris, Thomas,Bobovski, Thomas P.,Schwender, Charles F.
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p. 5723 - 5727
(2007/10/02)
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