IP Library Granted Patent US 9,133,183
Granted Patent B2
US 9,133,183 · App. 14/214,134 · Granted Sep 15, 2015

Imidazolidinones and analogs exhibiting anti-cancer and anti-proliferative activities

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Quick Facts
Patent No.
US 9,133,183
App. No.
14/214,134
Granted
Sep 15, 2015
Kind
B2
Abstract

Described are compounds of Formula I which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-1R), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c-FMS, c-KIT, or PDGFR kinases.

Claims (61)

1. A compound of Formula I,

or a pharmaceutically acceptable salt, enantiomer, stereoisomer, or tautomer thereof,

wherein

A is selected from the group consisting of C1-C6 alkyl, deutero-C1-C6 alkyl wherein the alkyl chain is partially or completely deuterated, branched C3-C8alkyl, fluoroC 1 -C6alkyl wherein the alkyl is fully or partially fluorinated, C3-C8carbocyclyl, and a 4-8 membered heterocyclic ring, and wherein the A moiety may be further substituted with one, two, or three R3 moieties;

W is C5-C6heteroaryl, —NHC(O)R6, —NHC(O)R7, —NHC(O)N(R8)R9, —C(O)R11, or phenyl, wherein the C5-C6heteroaryl and phenyl moieties are optionally substituted by one, two, or three R5;

each X1, X2, X3 and X4 is individually and independently hydrogen, C1-C6 alkyl, halogen, or fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated;

Z1 is N or CX3;

Z2 is CX4 or N;

Z3 is CH or N;

each R1 and R2 is individually and independently H, C1-C6 alkyl, fluoroC1-C6alkyl wherein the alkyl is fully or partially fluorinated, hydroxyl, C1-C6 alkoxy, fluoroC1-C6alkoxy wherein the alkyl group is fully or partially fluorinated, or cyano;

each R3 is individually and independently H, halogen, C1-C6 alkyl, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, branched C3-C8 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluoro-C1-C6 alkoxy wherein the alkyl chain is partially or completely fluorinated, branched C3-C6 alkoxy, hydroxyl, or cyano;

each R4 is individually and independently hydrogen, C1-C6 alkyl, or branched C3-C8 alkyl;

each R5 is individually and independently hydrogen, C1-C6 alkyl, deutero-C1-C6 alkyl wherein the alkyl chain is partially or completely deuterated, branched C3-C8 alkyl, halogen, cyano,

fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, —(CH 2 ) m —C(O)NR8(R9), —(CH 2 ) m —C(O)R7, —(CH 2 ) m —C(O)R6, —(CH 2 ) m —CN, —(CH 2 ) m —OR8, —(CH 2 ) m —NR8(R9), or —(CH 2 ) m —R7, wherein each alkylene may be further substituted with one or more C1-C6alkyl;

each R6 is individually and independently hydrogen, C1-C6 alkyl, branched C3-C8 alkyl, C3-C8 cycloalkyl, —(CH 2 ) m —CN, —(CH 2 ) m —OR8, —(CH 2 ) m —NR8(R9), or —(CH 2 ) m —R7, wherein each alkylene may be further substituted with one or more C1-C6alkyl;

each R7 is independently and individually selected from the group consisting of

and wherein the symbol (##) is the point of attachment to respective R5 or R6 moieties containing a R7 moiety;

each R7 is optionally substituted with —(R10) p ;

each R8 and R9 is individually and independently H, C1-C6 alkyl, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, or branched C3-C8 alkyl;

each R10 is individually and independently C1-C6 alkyl, —(CH 2 ) m —CN, —(CH 2 ) m —OR3, —(CH 2 ) m —NR8(R9), or —(CH 2 ) m —C(O)—R6, wherein each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;

R11 is —N(R8)R9 or R7;

each m is individually and independently 0, 1, 2, or 3;

each n is individually and independently 0, 1, 2, or 3;

each p is individually and independently 0, 1, 2, or 3; and

each q is individually and independently 0, 1, 2, or 3.

2. The compound of claim 1 , wherein W is selected from the group consisting of pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, —NHC(O)R6, —NHC(O)R7, —NHC(O)N(R8)R9, —C(O)N(R8)R9 and phenyl.

3. The compound of claim 2 , wherein the compound is a compound of Formula Ia,

or a pharmaceutically acceptable salt, enantiomer, stereoisomer, or tautomer thereof,

wherein the A moiety is selected from the group consisting of C1-C6 alkyl, branched C3-C8alkyl, fluoroC1-C6alkyl wherein the alkyl is fully or partially fluorinated, C3-C8-carbocyclyl, and a 4-8 membered heterocyclic ring.

4. The compound of claim 3 , wherein W is pyrazolyl, optionally substituted with —(R5) p .

5. The compound of claim 4 , wherein Z1 is N and X1 and X2 are independently selected from C1-C6alkyl and hydrogen.

6. The compound of claim 4 , wherein Z1 is CX3 and X1, X2 and X3 are individually and independently halogen, hydrogen, or C1-C6 alkyl.

7. The compound of claim 2 , wherein the compound is a compound of Formula Ib,

or a pharmaceutically acceptable salt, enantiomer, stereoisomer, or tautomer thereof,

wherein A is C1-C6 alkyl, branched C3-C8alkyl, fluoroC1-C6alkyl wherein the alkyl is fully or partially fluorinated, C3-C8carbocyclyl, or a 4-8 membered heterocyclic ring and q is 0 or 1.

8. The compound of claim 7 , wherein W is pyrazolyl, optionally substituted with —(R5) p .

9. The compound of claim 8 , wherein Z1 is N and X1 and X2 are independently selected from C1-C6alkyl or hydrogen.

10. The compound of claim 8 , wherein Z1 is CX3 and X1, X2 and X3 are individually and independently halogen, hydrogen, or C1-C6 alkyl.

11. The compound of claim 3 , wherein the compound is a compound of Formula Ic,

or a pharmaceutically acceptable salt, enantiomer, stereoisomer, or tautomer thereof.

12. The compound of claim 11 , wherein W is pyrazolyl, optionally substituted with —(R5) p .

13. The compound of claim 12 , wherein Z1 is N and X1 and X2 are independently selected from C1-C6alkyl or hydrogen.

14. The compound of claim 12 , wherein Z1 is CX3 and X1, X2 and X3 are individually and independently halogen, hydrogen, or C1-C6 alkyl.

15. The compound of claim 1 selected from the group consisting of N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro -2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-(1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran -4-yl)imidazolidine-1-carboxamide, 2-oxo-3-(tetrahydro-2H-pyran-4-yl)-N-(5-((2-(1-(trideuteromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)imidazolidine-1-carboxamide, N-(5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-(1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro -2H-pyran-4-yl)imidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl) -2-oxoimidazolidine-1-carboxamide, 3-(3-methoxypropyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, (S)—N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydrofuran-3-yl)imidazolidine-1-carboxamide, 3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridine -4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, 3-cyclohexyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, (S)-3-(1-methoxypropan-2-yl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-(1-methoxycyclopropyl)ethyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(3-methoxypropyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-3-(oxetan -3-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2-(trifluoromethoxy)ethyl)imidazolidine-1-carboxamide, 3-cyclohexyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, (S)—N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo -3-(tetrahydrofuran-3-yl)imidazolidine-1-carboxamide, 3-(3-methoxy-3-methylbutyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(4,4-difluorocyclohexyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(4,4-difluorocyclohexyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, (R)—N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydrofuran-3-yl)imidazolidine-1-carboxamide, (R)—N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo -3-(tetrahydrofuran-3-yl)imidazolidine-1-carboxamide, 3-cyclopentyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclopentyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclohexyl-4,4-dimethyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclohexyl-4,4-dimethyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(tert-butyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(tert-butyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-isopropyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-isopropyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, (R)—N-(6-methyl-5-((2-(1-(trideuteromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridine -2-yl)-2-oxo-3-(tetrahydrofuran-3-yl)imidazolidine-1-carboxamide, (S)-3-(1-methoxypropan-2-yl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridine-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-(trideuteromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 4-methyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, 3-methyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl) -2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, 3-methyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclopropyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclopropyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-3-(oxetan-3-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(6-methyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, N-(6-methyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro -2H-pyran-4-yl)imidazolidine-1-carboxamide, 3-(cyanomethyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, 3-cyclopentyl-N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1 -carboxamide, 3-cyclopentyl-N-(6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1 -carboxamide (R)-3-(1-methoxypropan-2-yl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2-(4-(1-methylpiperidin-4-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-ethyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, N-(6-ethyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, 3-cyclopropyl-N-(6-methyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-methyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)oxy)pyridine -2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclopropyl-N-(4,6-dimethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclopentyl-N-(4,6-dimethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-methyl-N-(6-methyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-methyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, 3-cyclopentyl-N-(6-methyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, N-(5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, 3-cyclopentyl-N-(6-ethyl-5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(4-(1-methylpiperidin-4-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, 3-methyl-N-(4-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl) -2-oxoimidazolidine-1-carboxamide, 3-cyclopropyl-N-(6-methyl-5-((2-(4-(1-methylpiperidin-4-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-methyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro -2H-pyran-4-yl)imidazolidine-1-carboxamide, 3-ethyl-N-(4-methyl-5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-methyl-N-(4-methyl-5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl) -2 -oxoimidazolidine-1-carboxamide, 4-((6-(3-(tert-butyl)-2-oxoimidazolidine-1-carboxamido)pyridin-3-yl)oxy)-N -methylpicolinamide, N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo -3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(2-fluoro-3-methyl-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo -3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(4-((2-(1H-pyrazol-4-yl)pyridin-4-yl)oxy)-5-chloro-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(3-chloro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(4-((2-acetamidopyridin-4-yl)oxy)-5-chloro-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(2-methoxyethyl)-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(2-(1-methoxycyclopropyl)ethyl)-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(2-methoxyethyl)-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-4-((2-(3,3-dimethylureido)pyridin-4-yl)oxy)-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(3-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(3-methoxypropyl)-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(oxetan-3-yl)-2-oxoimidazolidine-1-carboxamide, (S)—N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(1-methoxypropan-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo -3-(2-(trifluoromethoxy)ethyl)imidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-cyclohexyl-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(3-methoxy-3-methylbutyl)-2-oxoimidazolidine-1-carboxamide, N-(5-bromo-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo -3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(4,4-difluorocyclohexyl)-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-cyclopentyl-2-oxoimidazolidine-1-carboxamide, N-(5-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-3-(2-hydroxy-3,3-dimethylbutyl)-2-oxoimidazolidine-1-carboxamide, N-(3-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo -3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-chloro-4-((2-(2-cyanoacetamido)pyridin-4-yl)oxy)-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, 4-((6-(3-ethyl-2-oxoimidazolidine-1-carboxamido)pyridin-3-yl)oxy)-N -methylpicolinamide, N-(5-((2-(3,3-dimethylureido)pyridin-4-yl)oxy)pyridin-2-yl)-3-(2-methoxyethyl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(5-((2-(2-methyloxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-isopropyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2-acetamidopyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-(3,3-dimethylureido)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-acetamidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, and N-(5-((2-acetamidopyridin-4-yl)oxy)-6-methylpyridin-2-yl)-3-ethyl-2-oxoimidazolidine -1-carboxamide.

16. A pharmaceutical composition, comprising a compound of claim 15 and a pharmaceutically acceptable carrier.

17. A compound selected from the group consisting of 3-(tert-butyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(tert-butyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-isopropyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-isopropyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-methyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl) -2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, 3-ethyl-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-cyclopropyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2-(4-(1-methylpiperidin-4-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(6-methyl-5-((2-(4-(4-methylpiperazin-1-yl)phenyl)pyridin-4-yl)oxy)pyridine -2-yl)-2-oxoimidazolidine-1-carboxamide, 3-ethyl-N-(5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, N-(5-((2-(1-methyl-1H-imidazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(2,2,2-trifluoroethyl)imidazolidine-1-carboxamide, and 3-ethyl-N-(4-methyl-5-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide.

18. A pharmaceutical composition, comprising a compound of claim 17 and a pharmaceutically acceptable carrier.

19. A compound selected from the group consisting of 3-(2-methoxyethyl) -N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine -1-carboxamide, 3-(3-methoxypropyl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, (S)-3-(1-methoxypropan-2-yl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(3-methoxypropyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, (S)-3-(1-methoxypropan-2-yl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-(trideuteromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide, and (R)-3-(1-methoxypropan-2-yl)-N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide.

20. A pharmaceutical composition, comprising a compound of claim 19 and a pharmaceutically acceptable carrier.

21. A compound selected from the group consisting of N-(5-((2-(1-methyl -1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((2-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro -2H-pyran-4-yl)imidazolidine-1-carboxamide, 2-oxo-3-(tetrahydro-2H-pyran-4-yl)-N-(5-((2-(1-(trideuteromethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)imidazolidine-1-carboxamide, N-(5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H -pyran-4-yl)imidazolidine-1-carboxamide, N-(5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide, and N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide.

22. A pharmaceutical composition, comprising a compound of claim 21 and a pharmaceutically acceptable carrier.

23. The compound of claim 1 which is 3-ethyl-N-(6-methyl-5-((2-(1-methyl -1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide.

24. A pharmaceutical composition, comprising the compound of claim 23 and a pharmaceutically acceptable carrier.

25. The compound of claim 1 which is 3-(2-methoxyethyl)-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxoimidazolidine-1-carboxamide.

26. A pharmaceutical composition, comprising the compound of claim 25 and a pharmaceutically acceptable carrier.

27. The compound of claim 1 which is 3-methyl-N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2 -oxoimidazolidine-1-carboxamide.

28. A pharmaceutical composition, comprising the compound of claim 27 and a pharmaceutically acceptable carrier.

29. The compound of claim 1 which is N-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide.

30. A pharmaceutical composition, comprising the compound of claim 29 and a pharmaceutically acceptable carrier.

31. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

32. The composition of claim 31 further comprising an additive selected from adjuvants, excipients, diluents, or stabilizers.

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Dec 24, 2015
From: BRIGHTSTAR ASSOCIATES, LLC
To: DECIPHERA PHARMACEUTICALS, LLC
Reel/Frame 037359/0831 →
SECURITY INTEREST Recorded Aug 10, 2015
From: DECIPHERA PHARMACEUTICALS, LLC
To: BRIGHTSTAR ASSOCIATES LLC
Reel/Frame 036288/0037 →
SECURITY INTEREST Recorded Aug 10, 2015
From: DECIPHERA PHARMACEUTICALS, LLC
To: BRIGHTSTAR ASSOCIATES LLC
Reel/Frame 036315/0091 →
SECURITY INTEREST Recorded Aug 10, 2015
From: DECIPHERA PHARMACEUTICALS, LLC
To: BRIGHTSTAR ASSOCIATES LLC
Reel/Frame 036315/0188 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 6, 2014
From: FLYNN, DANIEL L.; KAUFMAN, MICHAEL D.; SAMARAKOON, THIWANKA; CALDWELL, TIMOTHY MALCOLM; VOGETI, LAKSHMINARAYANA; AHN, YU MI; PATT, WILLIAM C.; YATES, KAREN M.
To: DECIPHERA PHARMACEUTICALS, LLC
Reel/Frame 033895/0562 →