Chlorinated tetralin compounds and pharmaceutical compositions
The present disclosures are directed to chlorinated tetralin compounds and pharmaceutical compositions.
1 . A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 4 are independently hydrogen or halogen, and at least one of R 1 , R 2 , R 3 and R 4 is chloro.
2 . The compound of claim 1 , wherein the compound of Formula I is selected from the group consisting of:
(S)-2-(((S)-7-chloro-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl) amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide;
(S)-2-(((S)-6-chloro-8-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl) amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide; and
(S)-2-(((S)-8-chloro-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl) amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide.
3 . A pharmaceutical composition comprising a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 4 are independently hydrogen or halogen, and at least one of R 1 , R 2 , R 3 and R 4 is chloro.
4 . The pharmaceutical composition according to claim 3 , comprising a compound selected from the group consisting of:
(S)-2-(((S)-7-chloro-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl) amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide;
(S)-2-(((S)-6-chloro-8-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl) amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide; and
(S)-2-(((S)-8-chloro-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl) amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide.
5 . The pharmaceutical composition according to claim 3 , wherein the compound is(S)-2-(((S)-7-chloro-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl) amino)-N-(1-(2-methyl-1-(neopentylamino) propan-2-yl)-1H-imidazol-4-yl) pentanamide dihydrobromide, and the compound is present in an amount of about 1 μg to about 500 ug.
6 . The pharmaceutical composition according to claim 5 , wherein the compound is present in an amount of from about 5 μg to about 500 ug.
7 . The pharmaceutical composition according to claim 5 , wherein the compound is present in an amount of from about 10 μg to about 250 ug.
8 . The pharmaceutical composition according to claim 5 , wherein the compound is present in an amount of from about 10 μg to about 100 ug.
9 . The pharmaceutical composition according to claim 5 , wherein the compound is present in an amount of from about 10 μg to about 50 ug.
10 . The pharmaceutical composition according to claim 5 , wherein the compound is present in an amount of from about 12.5 ug to about 50 ug.
11 . The pharmaceutical composition according to claim 5 , further comprising a gamma-secretase inhibitor selected from the group consisting of nirogacestat, or a pharmaceutically acceptable salt thereof, crenigacestat, or a pharmaceutically acceptable salt thereof, AL101, or a pharmaceutically acceptable salt thereof, AL102, or a pharmaceutically acceptable salt thereof, semagacestat, or a pharmaceutically acceptable salt thereof, avagacestat, or a pharmaceutically acceptable salt thereof, and ianabecestat, or a pharmaceutically acceptable salt thereof.
12 . The pharmaceutical composition according to claim 5 , further comprising nirogacestat, or a pharmaceutically acceptable salt thereof.
13 . The pharmaceutical composition according to claim 5 , further comprising a pharmaceutically acceptable carrier.
14 . The pharmaceutical composition according to claim 5 , wherein the pharmaceutical composition is for oral administration.
15 . The pharmaceutical composition according to claim 5 , wherein the pharmaceutical composition is a tablet.
16 . The pharmaceutical composition according to claim 3 , further comprising a gamma-secretase inhibitor selected from the group consisting of nirogacestat or a pharmaceutically acceptable salt thereof, crenigacestat or a pharmaceutically acceptable salt thereof, AL101 or a pharmaceutically acceptable salt thereof, AL102 or a pharmaceutically acceptable salt thereof, semagacestat or a pharmaceutically acceptable salt thereof, and avagacestat or a pharmaceutically acceptable salt thereof.
17 . The pharmaceutical composition according to claim 3 , further comprising nirogacestat, or a pharmaceutically acceptable salt thereof.
18 . The pharmaceutical composition according to claim 4 , further comprising a gamma-secretase inhibitor selected from the group consisting of nirogacestat or a pharmaceutically acceptable salt thereof, crenigacestat or a pharmaceutically acceptable salt thereof, AL101 or a pharmaceutically acceptable salt thereof, AL102 or a pharmaceutically acceptable salt thereof, semagacestat or a pharmaceutically acceptable salt thereof, and avagacestat or a pharmaceutically acceptable salt thereof.
19 . The pharmaceutical composition according to claim 4 , further comprising nirogacestat, or a pharmaceutically acceptable salt thereof.