Compounds for alzheimer's disease
The invention provides novel compounds useful for the treatment of neurodegenerative disorders including Alzheimer's disease and dementia. The compounds have a substituents chosen from -L-C(═O)OH, -L-CH═CHC(═O)OH, -L-C(═O)NH 2 , -L-C(═O)NH(C 1-3 alkyl), -L-C(═O)N(C 1-3 alkyl) 2 , -L-S(═O) 2 (C 1-3 alkyl), -L-S(═O) 2 NH 2 , -L-S(═O) 2 N(C 1-3 alkyl) 2 , -L-S(═O) 2 NH(C 1-3 alkyl), -L-C(═O)NHOH, -L-C(═O)CH 2 NH 2 , -L-C(═O)CH 2 OH, -L-C(═O)CH 2 SH, -L-C(═O)NHCN, -L-NHC(═O)OR o , -L-C(═O)NHR o , -L-NH(C═O)NHR o , -L-C(═O)N(R o ) 2 , -L-NH(C═O)N(R o ) 2 , -L-sulfo, -L-(2,6 difluorophenol), -L-phosphono, and -L-tetrazolyl, where L is a linker.
1. A compound of Formula II, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition having such a compound,
Wherein one of R2 and R4 is —COOH, while the other is —H;
R1, R3, and R5, independent of one another, are chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3 alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3 alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1- 3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3 alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ;
R6 is hydro;
one of R7, R8 or R9 is haloalkyl, while the other two are, independent of one another, chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3 alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3 alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3 alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , —C(═O)—N-morpholino, -cyclohexyl, -morpholino, -pyrrolidinyl, -piperazinyl, —(N-methyl)-piperazinyl, —OCH 2 -phenyl, -pyridinyl, methylenedioxy, ethylenedioxy, —C(═O)OCH 2 CH 3 substituted furanyl, para-(C(═O)OCH 2 CH 3 )-phenyl, and —O—Si(CH 3 ) 2 (C(CH 3 ) 3 ); or optionally two adjacent of R6-R9 can be taken together to form a 4-7 member optionally substituted aryl or cycloalkyl ring;
R10 is hydro; and
R11 is an optionally substituted phenyl or heterocyclic group.
2. The compound of claim 1 wherein R1, R3, and R5, are independently chosen from hydro, hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3 alkyl) 2 , —NH(C 1-3 alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3 alkyl), —C(═O)N(C 1-3 alkyl) 2 , —S(═O) 2 (C 1-3 alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3 alkyl) 2 , —S(═O) 2 NH(C 1-3 alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , and —NO 2 ; and
R11 is an optionally substituted phenyl group.
3. The compound of claim 1 wherein
one of R7, R8 or R9 is trifluoromethyl.
4. The compound of claim 3 , wherein
R7 is trifluoromethyl.
5. The compound of claim 1 , wherein
R8 is trifluoromethyl.
6. The compound of claim 3 , wherein
R9 is trifluoromethyl.
7. The compound of claim 3 , wherein
R11 is a halo-substituted phenyl group.
8. The compound of claim 7 , wherein
R11 is a 3,4-dichloro-substituted phenyl group.
9. An orally available unit dosage form having a compound according to claim 1 .
10. The unit dosage form of claim 9 having from 1 mg to 2000 mg of said compound.
11. The unit dosage form of claim 9 having from 1 mg to 1000 mg of said compound.
12. The unit dosage form of claim 9 having from 1 mg to 800 mg of said compound.