Beta-carbolines useful for treating inflammatory disease
View Patent ↗This invention provides beta-carboline compounds of formula III-A-aa: wherein Q, G, R 1 , R 2 , R 3 , and R 6b are as described in the specification. The compounds are useful for treating diseases such as inflammatory diseases and cancer.
1. A compound of formula III-A-aa:
or a pharmaceutically acceptable salt thereof wherein,
Q is —CH 2 — or CH(R 9 );
G is morpholinyl optionally substituted by 1-2 R 10 ;
R 1 is hydrogen, halo,C 1-2 alkyl, amino, or (C 1-2 alkyl) 1-2 amino
R 2 is hydrogen, halo, C 1-2 aliphatic, C 1-2 alkoxy, or C 1-2 haloalkyl;
R 3 is hydrogen, halo, C 1-2 aliphatic, C 1-2 alkoxy, or C 1-2 haloalkyl;
each R 6b is independently methyl;
each R 7 is independently selected from hydrogen or C 1-4 aliphatic, or two R 7 on the same nitrogen atom are taken together with the nitrogen to form a 5-6 membered heteroaryl or heterocyclyl ring;
each R 8 is independently C 1-4 aliphatic;
each R 9 is independently selected from a C 1-3 aliphatic;
each R 10 is independently selected from R 11 , T-R 11 , or V-T-R 11 ;
each R 11 is independently selected from C 1-6 aliphatic, halo, —OR 7 , —CN, —SR 8 , —S(O) 2 R 8 , —C(O)R 7 , —CO 2 R 7 , —N(R 7 ) 2 , —C(O)N(R 7 ) 2 , —N(R 7 )C(O)R 7 , —N(R 7 )CO 2 R 7 , or —N(R 7 )C(O)N(R 7 ) 2 ;
T is a straight or branched C 1-4 alkylene chain; and
V is —O—, —N(R 7 )—, —S—, —S(O) 2 —, —C(O)—, or —CO 2 —.
2. The compound of claim 1 , wherein the compound has the (S) stereochemistry and is represented by the structure (S)-III-A-aa:
3. The compound of claim 2 , wherein the optionally substituted morpholinyl group is N-morpholinyl.
4. The compound of claim 3 where:
G is unsubstituted or is substituted by 1-2 groups independently selected from: C 1-3 alkyl, HO-alkyl, alkoxycarbonyl, mono- or dialkylaminocarbonyl, or HO 2 C-alkyl; and
R 6b is methyl.
5. A compound selected from:
6. A pharmaceutical composition comprising a compound of claim 1 , 2 , 3 , 4 , or 5 , and a pharmaceutically acceptable carrier.