Fused aminodihydrothiazine derivatives
AssigneeEisai R&D Management Co., Ltd.
InventorsAdrian Hall, Christopher Neil Farthing, Jose Luis Castro Pineiro
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Abstract
The present invention relates to a fused aminodihydrothiazine derivative of formula (I): wherein X is hydrogen or fluorine; A is CH or N; Y is methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, methoxy, ethoxy, methoxymethyl or —C≡N; and pharmaceutically acceptable salts thereof; which compound has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.
Claims11
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein
- X is hydrogen or fluorine;
- A is CH or N;
- Y is methyl, ethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoroethyl, methoxy, ethoxy, methoxymethyl or —C≡N.
A compound selected from the group consisting of:
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro -4H-furo [3 ,4-d] [1, 3] thiazin-7a-yl)-4- fluorophenyl)-5-cyanopicolinamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-(trifluoromethyl) picolinamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-methylpyrazine-2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-methylpicolinamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-ethylpicolinamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-methoxypicolinamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-ethoxypyrazine-2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-(1,1-difluoroethyl)pyrazine-2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-(trifluoromethyl)pyrazine-2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4-fluorophenyl)-5-(methoxymethyl)pyrazine-2-carboxamide;
- N-{3-[(4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5-dihydro-4H-furo[3,4d] [1,3] thiazin-7 a(7H)-yl ] -4- fluorophenyl} -5-[(2H3)methyloxy] pyrazine-2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4,5-difluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4,5-difluorophenyl)-5-methoxypyrazine -2-carboxamide;
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4,5-difluorophenyl)-5-methylpyrazine -2-carboxamide;
- and
- N-(3-((4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [1,3] thiazin-7a-yl)-4,5-difluorophenyl)-5-(fluoromethyl) -pyrazine-2-carboxamide;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.