Fused aminodihydrothiazine derivatives
A compound represented by the general formula: or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C 6-14 aryl group or the like, L is —NR e CO— or the like (wherein R e is a hydrogen atom or the like), Ring B is a C 6-14 aryl group or the like, X is a C 1-3 alkylene group or the like, Y is a single bond or the like, Z is a C 1-3 alkylene group or the like, R 1 and R 2 are each independently a hydrogen atom or the like, and R 3 , R 4 , R 5 and R 6 are independently a hydrogen atom, a halogen atom or the like, 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.
1. A compound represented by the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 3 and R 4 are independently selected from the group consisting of H and C 1-6 alkyl, wherein the C 1-6 alky is optionally substituted by 1, 2, or 3 substituents;
R 7a , R 7b , and R 7C are independently selected from the group consisting of H and X;
R 8a , R 8b , and R 8C are independently selected from the group consisting of H, X, CH m X n , and OCH m X n ; wherein
m is 0, 1, or 2;
n is 1, 2, or 3; and
X is halogen selected from the group consisting of fluorine, chlorine, bromine and iodine.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are H; and only one of R 7a , R 7b , and R 7C is X.
3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 8a , R 8b , and R 8C are independently selected from the group consisting of H, X, and CH m X n .
4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 7b and R 7c are H and R 7a is X.
5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 8a , R 8b , and R 8C are independently selected from the group consisting of H and X.
6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 8a and R 8C are H and R 8b is X.
7. The compound of claim 6 , wherein R 7a is fluorine.
8. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 7 as an active ingredient.
9. A method of treating a neurodegenerative disease, comprising administering an effective amount of the pharmaceutical composition according to claim 8 to a subject in need thereof, wherein the neurodegenerative disease is Alzheimer-type dementia or Down's syndrome.
10. A method of treating Alzheimer's disease, comprising administering an effective amount of the pharmaceutical composition according to claim 8 to a subject in need thereof.