6-, 7-, or 8-substituted quinazolinone derivatives and compositions comprising and methods of using the same
Provided are quinazolinone compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof: wherein R 7 , R 8 , and R 9 are as defined herein. Methods of use, and pharmaceutical compositions of these compounds are also disclosed herein.
1. A compound of formula (II):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 7 is : halo; —(CH 2 ) n OH; or
(C 1 -C 6 )alkoyl, optionally substituted with one or more halo; or
—(CH 2 ) n NHR d , wherein R d is:
hydrogen;
(C 1 -C 6 )alkyl, optionally substituted with one or more halo;
—(CH 2 ) n —(6 to 10 membered aryl);
—C(O)—(CH 2 ) n —(6 to 10 membered aryl) or —C(O)—(CH 2 ) n —(6 to 10 membered heteroaryl), wherein the aryl or heteroaryl is optionally substituted with one or more of: halo; —SCF 3 ; (C 1 -C 6 )alkyl, itself optionally substituted with one or more halo; or (C 1 -C 6 )alkoxy, itself optionally substituted with one or more halo;
—C(O)—(C 1 -C 8 )alkyl, wherein the alkyl is optionally substituted with one or more halo;
—C(O)—(CH 2 ) n —(C 3 -C 10 -cycloalkyl);
—C(O)—(CH 2 ) n —NR e R f , wherein R e and R f are each independently:
hydrogen;
(C 1 -C 6 )alkyl, optionally substituted with one or more halo;
(C 1 -C 6 )alkoxy, optionally substituted with one or more halo; or
6 to 10 membered aryl, optionally substituted with one or more of:
halo; (C i -C 6 )alkyl, itself optionally substituted with one or more halo; or (C 1 -C 6 )alkoxy, itself optionally substituted with one or more halo;
—C(O)—(CH 2 ) n —(C 1 -C 6 )alkyl; or
—C(O)—(CH 2 ) n —(CH 2 ) n -(6 to 10 membered aryl);
R 8 is: hydrogen; —(CH 2 ) n OH; phenyl; —O—(C i -C 6 )alkyl; or (C 1 -C 6 )alkyl, optionally substituted with one or more halo;
R 9 is: hydrogen; or (C 1 -C 6 )alkyl, optionally substituted with one or more halo; and
n is 0, 1, or 2.
2. The compound of claim 1 , having a structure of formula (III):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R 10 is: halo; —(CH 2 ) n OH; or (C 1 -C 6 )alkoxy, optionally substituted with one or more halo;
R 11 is: hydrogen; —(CH 2 ) n OH; phenyl; —O—(C 1 -C 6 )alkyl; or (C 1 -C 6 )alkyl, optionally substituted with one or more halo;
R 12 is: hydrogen; or (C 1 -C 6 )alkyl, optionally substituted with one or more halo; and
n is 0, 1, or 2.
3. The compound of claim 2 , wherein R 10 is a halogen or hydroxyl.
4. The compound of claim 2 , wherein R 11 is hydrogen or methyl.
5. The compound of claim 2 , wherein R 12 is hydrogen or methyl.
6. The compound of claim 2 , which is:
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof
7. The compound of claim 1 having a structure of formula (IV):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R g is:
hydrogen;
(C 1 -C 6 )alkyl, optionally substituted with one or more halo;
—(CH 2 ) n —(6 to 10 membered aryl);
—C(O)—(CH 2 ) n —(6 to 10 membered aryl) or —C(O)—(CH 2 ) n —(6 to 10 membered heteroaryl), wherein the aryl or heteroaryl is optionally substituted with one or more of: halo; —SCF 3 ; (C 1 -C 6 )alkyl, itself optionally substituted with one or more halo; or (C 1 -C 6 )alkoxy, itself optionally substituted with one or more halo;
—C(O)—(C 1 -C 8 )alkyl, wherein the alkyl is optionally substituted with one or more halo;
—C(O)—(CH 2 ) n —(C 3 -C 10 -cycloalkyl);
—C(O)—(CH 2 ) n —NR h R i , wherein R h and R i are each independently:
hydrogen;
(C 1 -C 6 )alkyl, optionally substituted with one or more halo;
(C 1 -C 6 )alkoxy, optionally substituted with one or more halo; or
6 to 10 membered aryl, optionally substituted with one or more of: halo;
(C 1 -C 6 )alkyl, itself optionally substituted with one or more halo; or
1 (C 1 -C 6 )alkoxy, itself optionally substituted with one or more halo;
—C(O)—(CH 2 ) n —O—(C 1 -C 6 )alkyl; or
—C(O)—(CH 2 ) n —O—(CH 2 ) n -(6 to 10 membered aryl);
R 13 is: hydrogen; —(CH 2 ) n OH; phenyl; —O—(C 1 -C 6 )alkyl; or (C 1 -C 6 )alkyl, optionally substituted with one or more halo;
R 14 is: hydrogen; or (C 1 -C 6 )alkyl, optionally substituted with one or more halo; and
n is 0, 1, or 2.
8. The compound of claim 7 , wherein R g is hydrogen.
9. The compound of claim 7 , wherein R g is —C(O)—(C 1 -C 6 )alkyl.
10. The compound of claim 7 , wherein R g is —C(O)-phenyl, optionally substituted with one or more of methyl, halo, and (C 1 -C 6 )alkyl.
11. The compound of claim 7 , which is:
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
12. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.