Quinolone analogs
The present invention provides quinolone analogs which may inhibit cell proliferation and/or induce cell apoptosis. The present invention also provides methods of preparing quinolone analogs, and methods of using the same.
1. A compound having formula (1):
or a pharmaceutically acceptable salt thereof;
wherein A is absent if Z 3 is N, and H, halo or C 1-10 alkyl when Z 3 is C;
B is absent if Z 1 is N, or is H or halo if Z 1 is C;
V is H, halo or C 1-10 alkyl;
X is an amino substituent selected from an optionally substituted piperidine, pyrrolidine, piperazine, morpholine, or thiomorpholine ring, or is a C 1-10 thioalkyl group substituted with pyrazine;
Z 1 and Z 3 are each independently C or N;
Z 2 and Z 4 are both C;
Z is NR 1 or S;
W together with N and Z form a 5-membered ring that is fused to a phenyl ring of the formula
U is NR 1 R 2 or NR 1 —(CR 1 2 ) n —NR 3 R 4 ;
in each NR 1 R 2 , R 1 and R 2 together with N form an optionally substituted ring selected from piperidine, pyrrolidine, piperazine, morpholine, and thiomorpholine;
in NR 3 R 4 , R 3 and R 4 together with N may form an optionally substituted ring selected from piperidine, pyrrolidine, piperazine, morpholine, and thiomorpholine;
R 1 and R 3 are independently H or C 1-6 alkyl;
R 4 is H, a C 1-10 alkyl or C 2-10 alkenyl;
each R 5 is independently H, amino, alkoxy, amido, halogen, or cyano; or R 5 is C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl, each optionally substituted by halo; and
n is 1-6.
2. The compound of claim 1 , wherein U is NR 1 R 2 , wherein R 1 and R 2 together with N form an optionally substituted piperidine, pyrrolidine, piperazine, morpholine, or thiomorpholine ring.
3. The compound of claim 1 , wherein U is NR 1 —(CR 1 2 ) n —NR 3 R 4 ; n is 1-4; and R 3 and R 4 in NR 3 R 4 together form an optionally substituted piperidine, pyrrolidine, piperazine, morpholine, or thiomorpholine.
4. The compound of claim 1 , wherein U is NH—(CH 2 ) n —NR 3 R 4 wherein R 3 and R 4 together with N form an optionally substituted pyrrolidine.
5. The compound of claim 1 , wherein U is (2-pyrrolidin-1-yl)ethanamino.
6. The compound of claim 1 , wherein A is halo.
7. The compound of claim 1 , wherein X is a C 1-10 thioalkyl group substituted with pyrazine.
8. The compound of claim 1 , wherein each of Z 1 , Z 2 , Z 3 and Z 4 are C.
9. The compound of claim 1 , wherein three of Z 1 , Z 2 , Z 3 and Z 4 is C, and either Z 1 or Z 3 is N.
10. The compound of claim 1 , wherein Z 1 and Z 3 are N.
11. The compound of claim 1 , wherein Z 1 is N.
12. The compound of claim 1 , wherein R 1 is methyl.
13. The compound of claim 1 , wherein at least one of B, A, or V is halo, and the corresponding adjacent Z 1 , Z 3 or Z 4 is C.
14. The compound of claim 1 , wherein V is H.
15. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.
16. A compound having the formula
or a pharmaceutically acceptable salt thereof.
17. A pharmaceutical composition comprising the compound of claim 16 , and pharmaceutically acceptable carrier.