Rilyazine derivatives and compositions for the treatment of cancer
View Patent ↗The present application discloses Rilyazine analogs, methods for their preparation, and the treatment of cancer by the administration of an effective amount of the Rilyazine analogs to a patient in need thereof.
1. A compound selected from the group consisting of:
wherein:
each R 1 is independently selected from the group consisting of hydrogen, halo, nitro, trifluoromethyl, trifluoromethoxy, methoxy, carboxy, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH3)2, —SCH3, —CN, (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl and heteroaryl;
each R 2 is independently selected from the group consisting of hydrogen, (C 1 -C 12 )alkyl, (C 1 -C 12 )alkoxy, —C(O)(C 1 -C 12 )alkyl, (C 3 -C 10 )cycloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein each of (C 1 -C 12 )alkyl, (C 1 -C 12 )alkoxy, —C(O)(C 1 -C 12 )alkyl, (C 3 -C 10 )cycloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halo, nitro, trifluoromethyl, trifluoromethoxy, methoxy, carboxy, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , -SCH 3 , —CN, (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl and heteroaryl; and
each R 3 is independently selected from the group consisting of hydrogen, halo, nitro, trifluoromethyl, trifluoromethoxy, methoxy, carboxy, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —SCH 3 , —CN, (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl and heteroaryl;
as a single stereoisomer, a mixture of stereoisomers, and a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein:
each R 2 is independently selected from the group consisting of (C 1 -C 12 )alkyl, (C 1 -C 12 )alkyl-aryl, (C 1 -C 12 )alkoxy, —C(O)(C 1 -C 12 )alkyl, (C 3 -C 10 )cycloalkyl, aryl and heteroaryl, wherein each of (C 1 -C 12 )alkyl, (C 1 -C 12 )alkoxy, —C(O)(C 1 -C 12 )alkyl, (C 3 -C 10 )cycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halo, nitro, trifluoromethyl, trifluoromethoxy, methoxy, carboxy, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , -SCH 3 , —CN, (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl and heteroaryl.
3. The compound of claim 2 , wherein:
R 1 and R 3 are each hydrogen; and
each R 2 is independently selected from the group consisting of —CH 2 CH 3 , -cyclohexyl, —CH 2 C 6 H 5 , -phenyl, -2-pyridinyl and -CH 2 -2-pyridinyl.
4. The compound of claim 1 wherein:
the compound is RL-D;
R 1 and R 3 are each hydrogen; and
each R 2 is independently selected from the group consisting of (C 1 -C 12 )alkyl, (C 1 -C 12 )alkyl-aryl, (C 1 -C 12 )alkoxy, —C(O)(C 1 -C 12 )alkyl, (C 3 -C 10 )cycloalkyl, aryl and heteroaryl, wherein each of (C 1 -C 12 )alkyl, (C 1 -C 12 )alkoxy, —C(O)(C 1 -C 12 )alkyl, (C 3 -C 10 )cycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halo, nitro, trifluoromethyl, trifluoromethoxy, methoxy, carboxy, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —SCH 3 , —CN, (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl and heteroaryl.
5. The compound of claim 1 , wherein:
R 1 and R 3 are each hydrogen; and
each R 2 is independently selected from the group consisting of:
wherein R 4 and R 5 are each independently hydrogen, (C 1 -C 6 )alkyl, F, Cl, Br, I, nitro, trifluoromethyl, trifluoromethoxy, methoxy, carboxy, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —SCH 3 and —CN.
6. The compound of claim 5 , wherein:
R 4 is hydrogen; and
R 5 is 2-, 3- or 4-substituted with (C 1 -C 3 )alkyl;
as a single isomer or mixture of stereoisomers.
7. The compound of claim 1 selected from the group consisting of:
8. The compound of claim 7 , wherein the compound is:
9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , and a pharmaceutically acceptable excipient.