Composition and methods for treating glioblastoma
View Patent ↗The disclosure provides methods of treating glioblastoma, methods of screening for compounds that treat glioblastoma, and pharmaceutical compositions useful the treatment of glioblastoma.
1. A compound of formula:
or pharmaceutically acceptable salts, wherein
X is CH or N;
R 11 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, halogen, —NO 2 , —CN, —OR 15 , or —NR 16 R 17 , each being optionally substituted with one to four R 20 ;
R 12 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, halogen, —NO 2 , —CN, —OR 15 , or —NR 16 R 17 , each being optionally substituted with one to four R 20 ;
R 14 and R 13 taken together with the atoms to which they are attached form a 5-, 6-, or 7-membered heterocyclyl group optionally substituted with one to four R 20 ;
R 15 , R 16 , and R 17 are independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl
R 18 and R 19 are each independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halogen, —NO 2 , —CN, —OR 15 , or —NR 16 R 17 , each being optionally substituted with one to four R 20 ,
R 20 is halogen, —CN, —OH, —NO 2 , —NH 2 , —NH(C 1 -C 6 alkyl), —N(C 1 -C 6 alkyl) 2 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; and
m is an integer 1 or 2.
2. The compound according to claim 1 , wherein X is CH.
3. The compound according to claim 1 , wherein R 11 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy.
4. The compound according to claim 3 , wherein R 11 is methyl or methoxy.
5. The compound according to claim 1 , wherein R 12 is H.
6. The compound according to claim 1 , wherein R 13 and R 14 taken together with the atoms to which they are attached form a 6-membered heterocyclyl optionally substituted with one to four R 20 .
7. The compound according to claim 1 , wherein R 18 and R 19 are each independently H, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halogen, or —OH.
8. The compound according to claim 1 , which is:
9. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and one or more pharmaceutically acceptable diluents, preservatives, solubilizers, emulsifiers, adjuvants, excipients, or carriers.
10. The compound according to claim 1 , wherein R 12 is H or C 1 -C 6 alkyl optionally substituted with R 20 .