Aromatic heterocyclic compounds and their application in pharmaceuticals
Provided herein are novel aromatic heterocyclic compounds or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and their uses for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and methods for using such compounds or pharmaceutical compositions thereof to treat Alzheimer's disease.
1. A compound having Formula (I)
or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein:
m is 0, 1, 2 or 3;
n is 1, 2 or 3;
R 1 is F, Cl, Br or CF 3 ; R 2 is C 1-6 haloalkyl; R 4 is C 1-6 alkoxy; R 5 is
and wherein Q is N or CH and M is —NR 7 , and wherein R 7 is H, C 1-6 alkyl, C 3-6 cycloalkyl or oxetanyl; and each of A, X and Y is CH.
2. The compound according to claim 1 having Formula (II)
or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein:
m is 1, 2 or 3; and
n is 1.
3. The compound according to claim 1 , wherein R 2 is —CHF 2 , —CF 3 , —CH 2 CF 3 , —CF 2 CHF 2 , —CHFCF 3 , —CF 2 CF 3 , —CH 2 CF 2 CF 3 , or —CH 2 CF 2 CHF 2 .
4. The compound according to claim 1 , wherein each R 4 is independently methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, or tert-butoxy.
5. The compound according to claim 2 , wherein R 7 is H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , cyclopropyl, cyclobutyl, cyclopentyl, or oxetanyl.
6. The compound according to claim 1 having one of the following structures:
or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising the compound according to claim 1 , and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle or a combination thereof.