- PYRIDINYL AND PYRAZINYL-(AZA)INDOLSULFONAMIDES
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The present invention relates to pyridinyl and pyrazinyl-(aza)indolsulfonamides having GPR17 modulator activity. The compounds have utility in the treatment of a variety of GPR17-associated disorders.
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Page/Page column 59; 71-72
(2020/01/11)
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- Heterocyclic compounds
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The invention concerns pharmaceutically useful compounds of the formula I, in which A1, A2, A3, A4, B1, m, Ar, W, X, Y, Z and R1 have any of the meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel compounds possess endothelin receptor antagonist activity and are useful, for example, in the treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.
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- N-heterocyclyl sulphonamide derivatives and their use as endothelin antagonists
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The invention concerns pharmaceutically useful N-heterocyclyl sulphonamide derivatives, their pharmaceutically acceptable salts, processes for their manufacture, their use for antagonising one or more actions of endothelin in a human or other warm-blooded animal, their use in methods of treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role.
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- N-heterocyclic sulfonamides having endothelin receptor activity
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The invention concerns pharmaceutically useful compounds of the formula I, in which R 1, R 2, R 3, n, m and Het have any of the meanings defined herein, and their pharmaceutically-acceptable salts, and pharmaceutical compositions containing them. The novel compounds possess endothelin receptor antagonist activity and are useful, for example, in the treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role. The invention further concerns processess for the manufacture of the novel compounds and the use of the compounds in medical treatment.
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- New non-peptide endothelin-a receptor antagonists: Synthesis, biological properties, and structure-activity relationships of 5-(dimethylamino)-N- pyridyl-, -N-pyrimidinyl-, -N-pyridazinyl-, and -N-pyrazinyl-1- naphthalenesulfonamides
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Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamide endothelin-A (ETA) antagonist 5- (dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide (BMS 182874). In each of these heterocycles, a small substituent such as halogen para to the position of attachment to the sulfonamide nitrogen atom was found to be advantageous for ETA receptor affinity. Of these heterocycles, 2- pyrazines offered the greatest scope for improving receptor affinity. Optimization of the substituents at the 3- and 5-positions in the pyrazine ring led to potent, ET(A)-selective compounds such as 5-(dimethylamino)-N- (5-chloro-3-methoxy-2-pyrazinyl)-1-naphthalenesulfonamide (7m, ET(A) pIC50 8.1). When dosed orally at 10 mg/kg to conscious, normotensive rats infused with big ET-1, compounds such as 7m showed significant inhibition of the pressor response with a duration of effect lasting for the 5-h course of the experiment.
- Bradbury, Robert H.,Bath, Colin,Butlin, Roger J.,Dennis, Michael,Heys, Christine,Hunt, Sarah J.,James, Roger,Mortlock, Andrew A.,Sumner, Neil F.,Tang, Eric K.,Telford, Berwick,Whiting, Elaine,Wilson, Campbell
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p. 996 - 1004
(2007/10/03)
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