Cyanopyridine derivatives useful in the treatment of cancer and other disorders

1. A compound of Formula (I)

or a pharmaceutically acceptable acid salt or basic salt thereof,

wherein A is unsubstituted or substituted 2H,3H-benzo[e]1,4-dioxan-6-yl, 2H,4H-benzo[e]1,3-dioxan-6-yl, or 2H,4H-benzo[e]1,3-dioxan-8-yl wherein the substituents of the substituted 2H,3H-benzo[e]1,4-dioxan-6-yl, 2H,4H-benzo[e]1,3-dioxan-6-yl, or 2H,4H-benzo[e]1,3-dioxan-8-yl are substituted by (R 3 ) n wherein n is an integer 0, 1, 2, 3, 4, 5, or 6 and

each R 3 is independently

halogen,

R 4 ,

OR 4 ,

S(O)R 4 ,

C(O)R 4 ,

C(O)NR 4 R 5 ,

oxo,

cyano or

NO 2 ; and

R 4 and R 5 are independently hydrogen, C 1-6 alkyl, or up to per-halogenated C 1-6 alkyl,

B is selected from the group consisting of

p is an integer 0, 1, 2, 3, or 4, each R 1 is independently

halogen,

C 1-5 haloalkyl,

NO 2 ;

C(O)NR 4 R 5

C 1-6 alkyl,

C 1-6 dialkylamine,

C 1-3 alkylamine,

CN,

amino,

hydroxyl or C 1-3 alkoxy

SCH 3 ,

methylsulfonyl,

R 4 and R 5 are independently hydrogen, C 1-6 alkyl, or up to per-halogenated C 1-6 alkyl,

L is O or S,

m is an integer 0, 1, 2, or 3, and

each R 2 is independently C 1-5 alkyl, C 1-5 haloalkyl, C 1-3 alkoxy, N-oxo or N-hydroxy.

2. A compound of claim 1 , wherein L is oxygen.

3. A compound of claim 1 , wherein R 1 is fluorine, chlorine, bromine, methyl, NO 2 , C(═O)NH 2 , methoxy, trifluoromethyl.

4. A compound of claim 1 , wherein R 2 is methyl, ethyl, propyl, or oxygen.

5. A compound of claim 1 , wherein R 3 is trifluoromethyl, methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, chlorine, fluorine, bromine, cyano, methoxy, acetyl, trifluromethyl sulfonyl, trifuoromethoxy, or trifluoromethylthio.

6. A compound which is

{[4-(2-cyano(4-pyridyloxy))-2-(trifluoromethyl)phenyl]amino}-N-(2,2,3,3-tetrafluorobenzo[e]1,4-dioxan-6-yl)carboxamide;

{[2-chloro-4-(2-cyano(4-pyridyloxy))phenyl]amino}-N-(2,2,3,3-tetrafluorobenzo[e]1,4-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2-fluorophenyl]amino}-N-(2,2,3,3-tetra-fluorobenzo[e]1,4-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2,6-difluorophenyl]amino}-N-(2 ,2,3 ,3-tetrafluorobenzo[e]1,4-dioxan-6-yl )carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2,5-difluorophenyl]amino}-N-(2,2,3 ,3-t-etrafluorobenzo[e]1,4-dioxan-6-yl)carboxamide;

{[3-chloro-4-(2-cyano(4-pyridyloxy))phenyl]amino}-N-(2,2,3,3-tetrafluorobenzo[e]1,4-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2-methyl phenyl]amino}-N-(2,2,3,3-tetr-afluorobenzo[e]1,4-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-3- methyiphenyl]amino}-N-(2,2 ,3,3-tetrafluorobenzo[e]1,4-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2-nitrophenyl]amino}-N-(2,2,3,3-tetrafluo-robenzo[e]1,4-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))phenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2-fluorophenyl]amino}-N-(2,2,4,4-tetrafluorob-enzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[3-chloro-4-(2-cyano(4-pyridyloxy))phenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[2-chloro-4-(2-cyano(4-pyridyloxy))phenyl]amino}-N-(2,2,4,4-tetraflu-orobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-3-fluorophenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2-(trifluoromethyl)phenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2 ,3-difluorophenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2,- 5-difluorophenyl]amino}-N-(2,2 14,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2,6-difluorophenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyl)oxy)-3-methoxyphenyl]amino}-N-(2,2,4,4-tetrafluoro-benzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[3-bromo-4-(2-cyano(4-pyridyloxy))phenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-2-methylphenyl]amino}-N-(2,2,4,4-tetraflu-orobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyloxy))-3-methylphenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

5-(2-cyano(4-pyridyl )oxy)-2-{[N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl )carbamoyl]amino}benzamide

{[4-(2-cyano(4-pyridyloxy))-2-nitrophenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano-1 -hydroxy(4-pyridyloxy))phenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano-1 -hydroxy(4-pyridyloxy))-2-fluorophenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyl)oxy)-2-methylthiophenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl)carboxamide;

{[4-(2-cyano(4-pyridyl)oxy)-2-(methylsulfonyl)phenyl]amino}-N-(2,2,4,4-tetrafluorobenzo[3,4-e]1 ,3-dioxan-6-yl)carboxamide;

or a pharmaceutically acceptable salt thereof or an isolated stereolsomer thereof.

7. A compound of claim 1 , which is a pharmaceutically acceptable basic salt of an organic acid of formula (I).

8. A compound of claim 1 , which is a pharmaceutically acceptable acid salt of a compound of formula (I) which is a salt of an organic base or an inorganic base.

9. A compound of Formula Y

or a pharmaceutically acceptable salt thereof,

wherein Q is 2H,3H-benzo[e]1,4-dioxan-6-yl, 2H,4H-benzo[e]1,3-dioxan-6-yl, or 2H,4H-benzo[e]1,3-dioxan-8-yl, substituted with at least one halogen, each R 2 is independently C 1-5 alkyl, C 1-5 haloakyl, C 1-3 alkoxy, N-oxo or N-hydroxy; m is 0, 1, 2 or 3; and phenyl ring “B” is substituted by one or more fluorine atoms.

10. A compound of claim 9 wherein phenyl ring “B” is substituted by 2-4 fluorine atoms.

11. A compound of claim 9 wherein phenyl ring “B” is substituted by 2-4 fluorine atoms and Q is substituted by 2-4 fluorine atoms.

12. A compound of claim 9 wherein Q is 2,2,4,4-tetrafluorobenzo[3,4-e]1,3-dioxan-6-yl or 2,2,3,3-tetrafluorobenzo[e]1,4-dioxan-6-yl.

13. A compound of formula II below

wherein B of formula II is

wherein the urea group, —NH—C(O)—NH—, and the bridging group, L, are not bound to contiguous ring carbons of B, but rather have 1 or 2 ring carbons separating them,

A of the formula (II) is

wherein the variable n is 0,1,2,3, or 4, and R 3 is trifluoromethyl, methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, chlorine, fluorine, bromine, cyano, methoxy, acetyl, trifluoromethanesulfonyl, trifluoromethoxy, or trifluoromethylthio.

14. A compound of claim 13 wherein each R 3 substitutent is fluorine.

15. A compound of claim 13 wherein A of formula II is

and B of the formula II is phenylene, fluoro substituted phenylene or difluoro substituted phenylene.

16. A compound of formulae:

or a pharmaceutically acceptable salt thereof, or the nitrogen atom in the pyridine group is in the oxide form,

wherein

each R 1 is independently halogen or trifluoromethyl and each R 3 is independently halogen, R 4 , OR 4 , S(O)R 4 , C(O)R 4 , C(O)NR 4 R 5 , oxo

or cyano or nitro (NO 2 ),

the variable n is 0, 1, 2, 3 or 4 and

the variable p is 0, 1 or 2.

17. A compound as in claim 16 wherein R 3 is fluoro, trifluoromethyl, methyl or t-butyl.

18. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a physiologically acceptable carrier.