Substituted pyrrolo[2,3-d]pyrimidines for the treatment of cancer and proliferative disorders
Disclosed are substituted pyrrolo[2,3-d]pyrimidine compounds. The disclosed compounds are shown to be useful in inhibiting the growth of cancer cell lines and treating cancer and cell proliferative disorders and have a general Formula I as indicated:
1. A compound having a Formula I:
wherein:
R 2 is hydrogen, halogen, or amino;
R 4 is hydrogen, halogen, amino, or C 1 -C 3 alkyl optionally substituted at one or more positions with halogen;
R 5 and R 6 are each independently hydrogen, or C 1 -C 3 alkyl optionally substituted at one or more positions with halogen; wherein at least one of R 5 and R 6 is trifluoromethyl;
R 7 is —(CH 2 ) n — where n is 1 or 2;
R 8 is methoxy, amino, or a 4-, 5-, or 6-membered carbocyclic or heterocyclic ring that is saturated or unsaturated, the carbocyclic or heterocyclic ring optionally substituted at one or more carbon atoms with halogen, hydroxyl, methoxy, oxo, methylcarboxyl, methylamido, or methylhydroxyl; and the heterocyclic ring is optionally substituted at a nitrogen heteroatom with a substituent selected from
C 1 -C 3 alkyl,
or
R 8 is selected from
2. The compound of claim 1 , wherein R 4 is halogen.
3. The compound of claim 2 , wherein R 4 is chlorine.
4. The compound of claim 1 having a Formula IA:
wherein: R 2 , R 4 , R 6 , and R 8 are as defined for Formula I.
5. The compound of claim 4 , wherein R 8 is a ring selected from piperidinyl, phenyl, pyridinyl, and oxanyl, which may be substituted at one or more carbon atoms with halogen or methoxy, and which may be substituted at a nitrogen heteroatom with a substituent selected from
6. A compound having a formula selected from:
7. The compound of claim 1 having a Formula IB:
wherein: R 2 , R 4 , R 6 , and R 8 are as defined for Formula I.
8. The compound of claim 7 , wherein R 8 is a ring selected from piperidinyl, phenyl, pyridinyl, and oxanyl, which may be substituted at one or more carbon atoms with halogen or methoxy, and which may be substituted at a nitrogen heteroatom with a substituent selected from
9. The compound of claim 7 , having a formula selected from:
10. A pharmaceutical composition comprising an effective amount of the compound of claim 1 together with a carrier, excipient, or diluent.
11. A compound having a Formula I:
wherein:
R 2 is hydrogen, halogen, or amino;
R 4 is hydrogen, hydroxyl, halogen, acetyl, amino, methylsulfonyl, cyano, or C 1 -C 3 alkyl optionally substituted at one or more positions with halogen;
R 5 and R 6 are each independently hydrogen, halogen, amino, or C 1 -C 3 alkyl optionally substituted at one or more positions with halogen; wherein at least one of R 5 and R 6 is C 1 -C 3 alkyl substituted at one or more positions with halogen;
R 7 is —(CH 2 ) n — where n is 1, 2, or 3;
R 8 is hydrogen, C 1 -C 3 alkyl optionally substituted at one or more positions with halogen, C 1 -C 3 alkoxy, amino, or a saturated 4-, 5-, or 6-membered carbocyclic or heterocyclic ring, the carbocyclic or heterocyclic ring optionally substituted at one or more carbon atoms with halogen, hydroxyl, methoxy, oxo, methylcarboxyl, methylamido, or methylhydroxyl; and the heterocyclic ring is optionally substituted at a nitrogen heteroatom with a substituent selected from
C 1 -C 3 alkyl,
or
R 8 is selected from
12. A compound having a formula:
wherein:
R 2 is hydrogen, halogen, or amino;
R 4 is hydrogen, hydroxyl, halogen, acetyl, amino, methylsulfonyl, cyano, or C 1 -C 3 alkyl optionally substituted at one or more positions with halogen;
R 5 and R 6 are each independently hydrogen, amino, or C 1 -C 3 alkyl optionally substituted at one or more positions with halogen;
R 7 is —(CH 2 )—;
R 8 is piperidin-4-yl optionally substituted at the nitrogen heteroatom with a substituent selected from
13. The compound of claim 12 , having a formula selected from:
14. The compound of claim 12 having a Formula IF:
wherein:
R 2 is hydrogen, halogen, or amino;
R 4 is halogen; and
R 9 is hydrogen, or R 9 is selected from
15. The compound of claim 14 , having a formula selected from:
16. A pharmaceutical composition comprising an effective amount of the compound of claim 6 together with a carrier, excipient, or diluent.
17. A pharmaceutical composition comprising an effective amount of the compound of claim 11 together with a carrier, excipient, or diluent.
18. A pharmaceutical composition comprising an effective amount of the compound of claim 12 together with a carrier, excipient, or diluent.