Alpha-7 nicotinic acetylcholine receptor modulators and uses thereof-I
View Patent ↗The present invention relates to chemical compounds of formula (I), with the substituents as described in the specification, useful in the positive modulation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR). The invention also relates to the use of these compounds in the treatment or prevention of a broad range of diseases in which the positive modulation of α7 nAChR is advantageous, including neurodegenerative and neuropsychiatric diseases and also neuropathic pain and inflammatory diseases.
1. A compound represented by formula (Ia′), or a pharmaceutically acceptable salt thereof:
wherein
n is 1;
R 2 is selected from C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, phenyl, F, or Cl;
R 3 is selected from hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, F, Cl, or CN; or
R 2 and R 3 together form C 4-9 cycloalkyl or C 4-9 cycloalkenyl;
R 4 is selected from optionally substituted heteroaryl, optionally substituted heterocyclyl, or optionally substituted aryl; and
R 5 is independently selected from hydrogen, or C 1 -C 4 alkyl;
wherein the optional substituents are each independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, —OH, phenyl, benzyl, phenoxy, benzyloxy, benzoyl, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl) 2 , —CN, —NO 2 , mercapto, —P═O(OH)NH 2 , —S(O) 2 NH 2 , —S(O) 2 NHC 1-4 alkyl, —S(O) 2 N(C 1-4 alkyl) 2 , C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, CO 2 H, —S(O)R′″, and —S(O) 2 R″″, wherein R′″ is lower alkyl or cycloalkyl and wherein R″″ is lower alkyl, cycloalkyl or OH.
2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 and R 3 are both C 1 -C 3 alkyl (preferably methyl), or R 2 and R 3 together form a C 4 -C 9 cycloalkyl ring.
3. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 and R 3 are both F.
4. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 and R 3 are both methyl.
5. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 is methyl, and R 3 is hydrogen.
6. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 and R 3 together form a C 4 -C 9 cycloalkyl ring, preferably cyclopentyl or cyclohexyl ring.
7. A compound or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, represented by the following: