Raf inhibitor compounds
AssigneeEli Lilly and Company
InventorsDaniel L. Flynn, Michael D, Kaufman, Lakshminarayana Vogeti, Scott Wise, Wei-Ping Lu, Bryan Smith, Timothy Malcolm Caldwell, William C. Patt, James R. Henry, Philip A. Hipskind, Sheng-Bin Peng
Life of this patent
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Abstract
This invention provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I); and use of a compound of Formula (I) for treating specified cancers.
Claims20
A compound of formula I
- wherein
- W is C1-C6 alkyl, optionally substituted with one or more of Z1A, Z1B, Z1C, Z1D, or Z1E;
- C4-C8 cycloalkyl optionally substituted with one or two Z2A or Z2B substituents;
- or W is C4-C8 heterocyclyl optionally substituted with one or two Z2A or Z2B substituents;
- each Z1A, Z1B, Z1C, Z1D, Z1E is individually and independently C1-C6 alkyl, halogen, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, C1-C4alkoxy, hydroxyl, fluoroC1-C4alkoxy wherein the alkyl chain is partially or completely fluorinated, cyano, C3-C8 cycloalkyl optionally substituted with one or two Z2A or Z2B substituents, phenyl optionally substituted with one to three Z2A or Z2B, or R5;
- each Z2A and Z2B is individually and independently hydrogen, C1-C6 alkyl, halogen, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, hydrogen, C1-C4alkoxy, hydroxyl, or cyano;
- X1 is fluoro or H;
- X2 is methyl, halogen, or hydrogen;
- R1 is selected from C1-C4alkyl, or hydrogen;
- R2 is C1-C6 alkyl, hydrogen, —(CH2)n—OR3, —(CH2)n—NR3(R4), —(CH2)q—R5, —C(O)—R7, or R6-substituted C5-C6heteroaryl;
- each R3 and R4 is individually and independently H, C1-C6 alkyl;
- each R5 is independently and individually selected from the group consisting of
- and wherein the symbol (##) is the point of attachment to —(CH2)q— or Z1A-E;
- each R5 is optionally substituted with —(R6)p;
- each R6 is individually and independently C1-C6 alkyl, —(CH2)m—CN, —(CH2)m—OR3, —(CH2)m—NR3(R4), —(CH2)m—C(O)NR3(R4), or —(CH2)m—C(O)—R3, wherein each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;
- R7 is C1-C6alkyl, C3-C8 cycloalkyl, hydrogen, —(CH2)m—NR3(R4), —(CH2)m—R5, or —(CH2)m—OR3;
- each m is individually and independently 0, 1, 2, or 3;
- n is 2, 3, or 4;
- p is 0, 1, 2, 3, or 4;
- q is 0, 1, or 2.
A compound selected from 1-(3,3-dimethylbutyl)-3-(2-fluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-cyano-3-methylbutyl)-3-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3,3-dimethylbutyl)-3-(5-(2-ethyl-7-(methylamino)-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)urea, 1-(3,3-dimethylbutyl)-3-(5-(2-ethyl-7-(methylamino)-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)urea, 1-cycloheptyl-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3,3-dimethylbutyl)-3-(4-methyl-3-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3,3-dimethylbutyl)-3-(5-(2-ethyl-7-(methylamino)-1,6-naphthyridin-3-yl)-2-fluorophenyl)urea, 1-cycloheptyl-3-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-cyano-3-methylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-cyano-3-methylbutyl)-3-(2-fluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-(trifluoromethoxy)ethyl)urea, 1-(4,4-difluorocyclohexyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-((3,3-dimethylcyclobutyl)methyl)urea, 1-(3,3-dimethylcyclobutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3,3-dimethylcyclobutyl)-3-(2-fluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3-methyl-trans(3-fluorocyclobutyl))urea, 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3,3-dimethylbutyl)urea, 1-(3,3-dimethylbutyl)-3-(4-fluoro-3-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-((3,3-dimethylcyclobutyl)methyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(4,4-difluorocyclohexyl)-3-(2-fluoro-4-methyl-5-(7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-(1-(trifluoromethyl)cyclopropyl)ethyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea, 1-(trans-4-cyano-4-methylcyclohexyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(cis-4-cyano-4-methylcyclohexyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-(1-methylcyclopropyl)ethyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-(1-methoxycyclopropyl)ethyl)urea, 1-(cyclohexylmethyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-ethoxy-3-methylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-(1-methoxycyclopropyl)ethyl)urea, 1-(2-fluoro-4-methyl-5-(7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(4-methoxy-4-methylpentyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-((6-methylpyridin-3-yl)amino)-1,6-naphthyridin-3-yl)phenyl)-3-(3,3-dimethylbutyl)urea, N-(3-(5-(3-(3,3-dimethylbutyl)ureido)-2-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide,
- N-(3-(3-(3-(3,3-dimethylbutyl)ureido)-4-fluorophenyl)-2-ethyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(5-(3-(3,3-dimethylbutyl)ureido)-2-fluorophenyl)-2-ethyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(4-fluoro-3-(3-(3-fluoro-3-methylbutyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)isobutyramide, N-(3-(5-(3-(4,4-difluorocyclohexyl)ureido)-4-fluoro-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(5-(3-(2-cyclopropylethyl)ureido)-4-fluoro-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(3-(3-(4,4-difluorocyclohexyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(4-fluoro-2-methyl-5-(3-(2-(trifluoromethoxy)ethyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(5-(3-(3-cyano-3-methylbutyl)ureido)-2,4-difluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide,
- 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-cyano-3-methylbutyl)urea, 1-(3-fluoro-3-methylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-fluoro-cis(3-methylcyclobutyl))-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea,
- 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3,3-dimethylcyclobutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-fluoro-3-methylbutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-methoxy-3-methylbutyl)urea, 1-(5-(7-amino-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-fluoro-3-methylbutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-cycloheptylurea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(2-(1-(trifluoromethyl)cyclopropyl)ethyl)urea, 1-(2-cyclopropylethyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-cycloheptyl-3-(2-fluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-fluoro-3-methylbutyl)-3-(2-fluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3,3,3-trifluoropropyl)urea, difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(4,4-difluorocyclohexyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(4,4,4-trifluoro-3,3-dimethylbutyl)urea, difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(4,4,4-trifluorobutyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3,3,3-trifluoropropyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea, 1-(3-fluoro-3-methylbutyl)-3-(2-fluoro-4-methyl-5-(7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-(1-methylcyclopropyl)ethyl)urea,
- 1-(5-(7-(ethylamino)-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-fluoro-3-methylbutyl)urea, 1-(3-fluoro-3-methylbutyl)-3-(2-fluoro-5-(7-(isopropylamino)-2-methyl-1,6-naphthyridin-3-yl)-4-methylphenyl)urea, 1-(2-cyclobutylethyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-cyclobutylethyl)-3-(2-fluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(4,4-difluoropentyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-fluoro-trans(3-methylcyclobutyl))-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(4-fluoro-4-methylpentyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(4,4,4-trifluoro-3,3-dimethylbutyl)urea, N-(3-(3-(3-(3,3-dimethylbutyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(5-(3-(3,3-dimethylbutyl)ureido)-4-fluoro-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(5-(3-(3,3-dimethylbutyl)ureido)-2,4-difluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide,
- N-(3-(5-(3-(3,3-dimethylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(3-(3-cycloheptylureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(3-(3-cyclohexylureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(3-(3-cyclopentylureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(3-(3-(2-cyclopentylethyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(3-(3-(2-cyclopropylethyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide,
- N-(3-(3-(3-(3,3-dimethylcyclobutyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(4-fluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)propionamide, N-(3-(2,4-difluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide,
- N-(3-(2,4-difluoro-5-(3-(3-hydroxy-3-methylbutyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(4-fluoro-2-methyl-5-(3-(3,3,3-trifluoropropyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(4-fluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, N-(3-(4-fluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(4-fluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)isobutyramide,
- N-(3-(4-fluoro-3-(3-(3,3,3-trifluoropropyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(2,4-difluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide,
- N-(3-(2,4-difluoro-5-(3-(4,4,4-trifluorobutyl)ureido)phenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(5-(3-(2-cyclopropylethyl)ureido)-2,4-difluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)cyclopropanecarboxamide, N-(3-(4-fluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)formamide, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3,3-dimethylbutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(4,4,4-trifluoro-3,3-dimethylbutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-(3,3-dimethylbutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3,3-dimethylbutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-(3-fluoro-3-methylbutyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-phenethylurea, 3-(3-(3-(3-(3,3-dimethylbutyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)-1,1-dimethylurea, N-(3-(3-(3-(3,3-dimethylbutyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)azetidine-1-carboxamide, 3-(3-(4-fluoro-5-(3-(3-fluoro-3-methylbutyl)ureido)-2-methylphenyl)-2-methyl-1,6-naphthyridin-7-yl)-1,1-dimethylurea, 1-(3,3-dimethylbutyl)-3-(2-fluoro-5-(7-((2-hydroxyethyl)amino)-2-methyl-1,6-naphthyridin-3-yl)-4-methylphenyl)urea, 1-(2,4-difluoro-5-(7-(2-hydroxyethylamino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)-3-(3,3-dimethylbutyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-isopentylurea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2,4,4-trimethylpentan-2-yl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-isopentylurea, 1-(3-fluoro-3-methylbutyl)-3-(2-fluoro-5-(7-((2-hydroxyethyl)amino)-2-methyl-1,6-naphthyridin-3-yl)-4-methylphenyl)urea, 1-((3,3-difluorocyclobutyl)methyl)-3-(2-fluoro-5-(7-((2-hydroxyethyl)amino)-2-methyl-1,6-naphthyridin-3-yl)-4-methylphenyl)urea, 1-(3-cyano-3-methylbutyl)-3-(2-fluoro-5-(7-((2-hydroxyethyl)amino)-2-methyl-1,6-naphthyridin-3-yl)-4-methylphenyl)urea, (S)-1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea, (R)-1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-morpholinoethyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-(1-hydroxycyclopropyl)ethyl)urea, 1-(4,4-dimethylpentan-2-yl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3-methylbutyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3,3,3-trifluoro-2-hydroxypropyl)urea, (R)-1-(4,4-dimethylpentan-2-yl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, (S)-1-(4,4-dimethylpentan-2-yl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)urea, 1-(3-cyano-3-methylbutyl)-3-(2,4-difluoro-5-(7-((2-hydroxyethyl)amino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2,4-difluoro-5-(7-((2-hydroxyethyl)amino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)-3-(3-fluoro-3-methylbutyl)urea, 1-(2,4-difluoro-5-(7-((2-hydroxyethyl)amino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)-3-((3,3-difluorocyclobutyl)methyl)urea, (R)-1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3-methylbutyl)urea, (S)-1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3-methylbutyl)urea, (R)-1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea, (S)-1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea, 1-(2-cyclopropyl-2-hydroxyethyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(oxetan-2-ylmethyl)urea, 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-((tetrahydro-2H-pyran-2-yl)methyl)urea, or 1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(tetrahydrofuran-3-yl)urea.
A compound selected from 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(2,4-difluoro-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(3,3-dimethylbutyl)urea, 1-(3-fluoro-3-methylbutyl)-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-fluoro-cis(3-methylcyclobutyl))-3-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, 1-(3-fluoro-3-methylbutyl)-3-(2-fluoro-4-methyl-5-(7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)urea, N-(3-(3-(3-(3,3-dimethylbutyl)ureido)-4-fluorophenyl)-2-methyl-1,6-naphthyridin-7-yl)acetamide, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(2-(1-(trifluoromethyl)cyclopropyl)ethyl)urea, 1-(5-(7-amino-2-methyl-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-fluoro-3-methylbutyl)urea, (S)-1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea, or (R)-1-(2-fluoro-4-methyl-5-(2-methyl-7-(methylamino)-1,6-naphthyridin-3-yl)phenyl)-3-(2-hydroxy-3,3-dimethylbutyl)urea.
Dependencies are inferred from the claim text.