Kinase inhibitors

1. A compound of formula I,

wherein

R 1A represents

C 1-6 alkoxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, which latter four groups are optionally substituted by one or more substituents selected from C 1-2 alkyl, halo, hydroxy, and C 1-2 alkoxy, H, halo, cyano,

phenyl or Het 1 , which latter two groups are optionally substituted with one or more substituents selected from C 1-2 alkyl and C 1-2 alkoxy,

or R 1A and R 1B together represent a structural fragment selected from the following

wherein the wavy lines represent the points of attachment to the phenyl ring,

A represents O, S or N(R A2 ),

R A1 represents H, C 1-4 alkyl or hydroxy,

R A2 represents H or C 1-4 alkyl;

R 1B represents —NR X S(O) 2 R Y1 , H, halo, cyano, —C 1-4 alkylene-CN, —C 1-4 alkylene-OH, —NR X R X1 , —C(O)OR X , —C(O)NR X R Y , —S(O) 2 NR X R Y , —NR X C(O)R Y , —NR X2 S(O) 2 NR X R Y , —NR X P(O)R Y1 R Y2 , —NR X C(O)OR Y1 or Het 1 optionally substituted with one or more substituents selected from halo, hydroxy, C 1-2 alkyl and C 1-2 alkoxy;

R X and R X1 independently represent H or C 1-6 alkyl, or R X and R X1 together represent C 3-6 n-alkylene or C 4-5 n-alkylene interrupted between C2 and C3 by —O— or —N(R X2 )—, or R X1 represents Het 1 optionally substituted with one or more substituents selected from halo, hydroxy, C 1-2 alkyl and C 1-2 alkoxy;

R Y , R Y1 and R Y2 independently represent C 1-6 alkyl, C 3-7 cycloalkyl, phenyl, benzyl, Het 1 or Het 2 , which latter six groups are optionally substituted by one or more substituents selected from C 1-2 alkyl, halo, hydroxy, C 1-2 alkoxy, NH 2 , N(H)—C 1-4 alkyl, N(C 1-4 alkyl) 2 , C(O)OH and C(O)O—(C 1-4 alkyl),

or R Y represents H,

or R X and R Y together represent C 3-6 n-alkylene or C 4-5 n-alkylene interrupted between C2 and C3 by —O— or —N(R X2 )—;

each R X2 independently represents H or C 1-4 alkyl;

R 1C and R 1E independently represent H, halo, cyano or methyl;

provided that at least one of R 1A , R 1B , R 1c and R 1E is other than H;

R 1D represents C 2-7 alkyl, trimethylsilyl, C 2-7 alkenyl, C 2-7 alkynyl, C 3-7 cycloalkyl, phenyl, Het 1 or Het 2 , which latter seven groups are optionally substituted by one or more substituents selected from C 1-2 alkyl, halo, cyano, hydroxy and C 1-2 alkoxy;

R 2 and R 3 , together with the C-atoms to which they are attached, form a fused phenyl or pyridyl ring, which latter two rings are optionally substituted by one or more substituents selected from C 1-3 alkyl, C 1-3 haloalkyl, cyano and halo,

or one of R 2 and R 3 represents H, halo, cyano, C 1-3 alkyl or C 1-3 haloalkyl and the other independently represents halo, cyano, C 1-3 alkyl or C 1-3 haloalkyl,

or R 2 and R 3 together combine to form C 3-5 alkylene or C 3-5 alkenylene, which latter two groups are optionally substituted by one or more substituents selected from C 1-3 alkyl, C 1-3 haloalkyl, cyano and halo;

X 1 represents N or CH;

L represents a direct bond or C 1-2 alkylene;

X 2 and X 3 both represent CR Z or one of X 2 and X 3 represents N and the other represents CR Z ;

R Z represents hydrogen, halo, cyano, hydroxy, C 1-3 alkyl or C 1-3 alkoxy, which latter two groups are optionally substituted by one or more halo atoms;

R 4 represents

—Q 1 -[C(R 6c )(R 6d )—(CH 2 ) 0-1 CH 2 —O] 1-12 —CH 2 (CH 2 ) 0-1 CH 2 —R 6a ,

-Q 2 -C(R 6c )(R 6d )—[C 1-5 alkylene]-R 6a , which C 1-5 alkylene group is optionally substituted by oxo,

—S(O) n R 6b ,

—COR 6b ,

—CH 2 OH,

or, when R 1B represents either —C(O)NR X R Y , in which R Y represents optionally substituted Het 1 or optionally substituted Het 2 , or —NR X2 S(O) 2 NR X R Y then R 4 may alternatively represent H, halo, cyano, hydroxy, C 1-3 alkyl or C 1-3 alkoxy, which latter two groups are optionally substituted by one or more halo atoms;

R 5 represents C 2-3 alkynyl, H, cyano, —C(O)NH 2 , hydroxy or halo, or R 5 represents C 1-3 alkoxy or C 1-3 alkyl, which latter two groups are optionally substituted by one or more halo atoms;

R 6a represents OR 7a , N(R 7b )R 7c or CO 2 H;

R 6b represents C 1-8 alkyl, C 3-8 cycloalkyl, phenyl, Het 1 or Het 2 , which latter five groups are optionally substituted by one or more substituents selected from halo, hydroxyl, C 1-3 alkyl and C 1-3 alkoxy;

R 6c and R 6d independently represent H or methyl;

R 7a to R 7c independently represent H or C 1-4 alkyl optionally substituted by one or more halo atoms, or R 7b and R 7c , together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated, partially unsaturated or fully aromatic and which heterocyclic group contains one N atom (the atom to which R 7b and R 7c are attached) and, optionally, one or more further heteroatoms selected from O, S and N, and which heterocyclic group is optionally substituted by one or more substituents selected from halo, hydroxy, oxo, C 1-4 alkyl and C 1-4 alkoxy;

Q 1 and Q 2 independently represent C(O)NH, O or S(O) p ; and

n and p independently represent 0, 1 or 2,

Het 1 represents, independently upon each occurrence, a 5- or 6-membered heterocyclic group that is fully aromatic, which group contains one or more heteroatoms selected from N, O and S;

Het 2 represents, independently upon each occurrence, a 4- to 7-membered heterocyclic group that is fully saturated or partially unsaturated, which group contains one or more heteroatoms selected from N, O and S;

or a pharmaceutically acceptable salt thereof.

2. A compound as claimed in claim 1 that is a compound of formula Ia, Ib or Ic,

or a pharmaceutically acceptable salt thereof, wherein R 1A to R 1E , R 2 to R 5 , X 1 to X 3 and R Z are as defined in claim 1 .

3. A compound as claimed in claim 1 , wherein R 1A represents H, halo, C 1-4 alkyl or C 1-4 alkoxy, which latter two groups are optionally substituted by one or more fluoro atoms.

4. A compound as claimed in claim 1 , wherein R 1B represents H, halo, cyano, —NR X R X1 , —C(O)OR X , —C(O)NR X R Y , —S(O) 2 NR X R Y , —NR X C(O)R Y , —NR X S(O) 2 R Y1 , —NR X C(O)OR Y1 , Het 1 , —NR X2 S(O) 2 NR X R Y , —CH 2 OH or —CH 2 CN.

5. A compound as claimed in claim 1 , wherein R X1 represents Het 1 or R X and R X1 independently represent H or C 1-4 alkyl, or R X and R X1 together represent C 4-5 n-alkylene optionally interrupted between C2 and C3 by —O— or —N(R X2 )—, wherein R X2 represents H or C 1-2 alkyl.

6. A compound as claimed in claim 1 , wherein

R Y represents H, benzyl or Het 2 optionally substituted by one or more substituents selected from methyl, halo, hydroxy and methoxy,

or R Y and R Y1 independently represent C 1-4 alkyl, C 3-6 cycloalkyl or phenyl, which latter three groups are optionally substituted by one or more substituents selected from methyl, halo, hydroxy, methoxy, NH 2 , N(H)—C 1-2 alkyl, N(C 1-2 alkyl) 2 , C(O)OH and C(O)O—(C 1-2 alkyl),

or R X and R Y together represent C 4-5 n-alkylene optionally interrupted between C2 and C3 by —O— or —N(R X2 )—, wherein R X2 represents H or C 1-2 alkyl.

7. A compound of formula I, as claimed in claim 1 , or a compound of formula Ia or Ib:

R 1A to R 1E , R 2 to R 5 , X 1 to X 3 and R Z are as defined in claim 1 .

8. A compound as claimed in claim 1 , wherein:

R 1D represents trimethylsilyl, C 3-7 alkyl, C(C 1-2 alkyl) 2 -C≡CH, C 3-5 cycloalkyl, phenyl or Het 2 , which latter three groups are optionally substituted by one or more substituents selected from C 1-2 alkyl, halo and C 1-2 alkoxy; and

Het 2 represents a 5- or 6-membered heterocyclic group that is fully saturated or partially unsaturated, which group contains one or two heteroatoms selected from N, O and S.

9. A compound as claimed in claim 1 , wherein:

R 2 and R 3 , together with the C-atoms to which they are attached, form a fused phenyl ring, or R 2 and R 3 independently represent halo or C 1-2 alkyl; and/or

L represents a direct bond or CH 2 .

10. A compound of formula I, as claimed in claim 1 , or a compound of formula Ia:

R 1A to R 1E , R 2 to R 5 and X 1 to X 3 are as defined in claim 1 .

11. A compound as claimed in claim 1 , wherein:

R 4 represents

-Q 1 -[C(R 6c )(R 6d )CH 2 —O] 1-8 —CH 2 CH 2 —R 6a ,

-Q 2 -C(R 6c )(R 6d )—[C 1-4 alkylene]-R 6a , which C 1-4 alkylene group is optionally substituted by oxo,

—S(O) n R 6b ,

—COR 6b ,

CH 2 OH;

or, when R 1B represents either —C(O)NR X R Y , in which R Y represents optionally substituted Het 2 , or —NR X2 S(O) 2 NR X R Y , then R 4 may alternatively represent H; and

n represents 0 or 2.

12. A compound as claimed in claim 1 , wherein R 5 represents H, cyano, chloro, fluoro, C 2-3 alkynyl, C 1-2 alkyl or C 1-2 alkoxy, which latter two groups are optionally substituted by one or more fluoro atoms.

13. A compound as claimed in claim 1 , wherein:

R 6a represents CO 2 H, OH, O—C 1-2 alkyl or N(R 7b )R 7c ; or

R 6b represents C 1-5 alkyl or C 3-5 cycloalkyl.

14. A compound as claimed in claim 1 , wherein R 7b and R 7c independently represent H or methyl, or R 7b and R 7c , together with the N-atom to which they are attached, form a 4- to 7-membered heterocyclic group that is fully saturated, which heterocyclic group contains one N atom (the atom to which R 7b and R 7c are attached) and, optionally, one further heteroatom selected from O, S and N, and which heterocyclic group is optionally substituted by one or more C 1-2 alkyl groups.

15. A compound as claimed in claim 1 , wherein Q 1 and Q 2

independently represent C(O)NH or O.

16. A compound as claimed in claim 1 , wherein:

R 1A represents H or C 1-2 alkoxy optionally substituted by one or more fluoro atoms;

R 1B represents H, cyano, —C(O)OH, —C(O)N(CH 3 ) 2 , fluoro, chloro, or, particularly, —C(O)N(H)R Y , —NHS(O) 2 CH 3 , —N(H)S(O) 2 NR X R Y or Het 1 ;

R Y represents H, Het 2 , C 3-5 cycloalkyl or C 1-3 alkyl, which latter group is optionally substituted by hydroxy, methoxy, NH 2 , N(H)CH 3 , N(CH 3 ) 2 or C(O)OCH 3 ,

or R X and R Y together represent C 4-5 n-alkylene optionally interrupted between C2 and C3 by —O—;

R 1D represents branched C 4-6 alkyl, morpholinyl or cyclopropyl optionally substituted by methyl;

R 2 and R 3 , together with the C-atoms to which they are attached, form a fused phenyl ring, or R 2 and R 3 both represent chloro;

R 4 represents

-Q 1 -[C(H)(R 6c )CH 2 —O] 1-6 —CH 2 CH 2 —R 6a ,

—C(O)NH—CH 2 —[C 1-2 alkylene]-R 6a ,

—S(O) 2 -cyclopropyl

or, when R 1B represents either —C(O)N(H)R Y , in which R Y represents Het 2 , or —N(H)S(O) 2 NR X R Y , then R 4 may alternatively represent H;

R 5 represents H, —C≡CH or methoxy, which latter group is optionally substituted by one or more fluoro atoms;

R 6a represents O—CH 3 or N(R 7b )R 7c ;

R 7b and R 7c both represent methyl, or R 7b and R 7c , together with the N-atom to which they are attached, form a piperazinyl group optionally substituted by methyl, a pyrrolidinyl group or a morpholinyl group;

Q 1 represents C(O)NH or O;

Het 1 represents a 5-membered heterocyclic group that is fully aromatic, which group contains one to three heteroatoms selected from N and O; and/or

Het 2 represents a 4- to 6-membered heterocyclic group that is fully saturated or partially unsaturated, which group contains one or two heteroatoms selected from N, O and S.

17. A compound as claimed in claim 1 which is a compound selected from the group consisting of:

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-ethynyl-N-(2-morpholinoethyl)benzamide;

3-ethynyl-5-((4-((4-(3-(3-fluoro-5-morpholinophenyl)ureido)naphthalen-1-yl)oxy)-pyrimidin-2-yl)amino)-N-(2-morpholinoethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)methane-sulfonamide;

N-(5-(tert-butyl)-3-(3-(4-((2-((3-(cyclopropylsulfonyl)-5-methoxyphenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxyphenyl)methanesulfonamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxy-N-(2-morpholinoethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxy-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide;

1-(5-(tert-butyl)-2-methoxyphenyl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

5-(tert-butyl)-3-(3-(4-((2-((3-ethynyl-5-((2-morpholinoethyl)carbamoyl)phenyl)amino) pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxy-N-methylbenzamide;

N-(5-(tert-butyl)-3-(3-(2,3-dichloro-4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)ureido)-2-methoxyphenyl)-methanesulfonamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)methane sulfonamide;

1-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)-pyrimidin-4-yl)oxy)naphthalen-1-yl)-3-(2-methoxy-5-morpholinophenyl)urea;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-N-methylbenz amide;

N-(3-(3-(4-((2-((3-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy)-5-methoxyphenyl)amino)-pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-5-(tert-butyl)-2-methoxyphenyl)-methanesulfonamide;

N-(5-(tert-butyl)-3-(3-(4-((2-((3-(2-(2-(2-(dimethylamino)ethoxy)ethoxy)ethoxy)-5-methoxyphenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxyphenyl)-methanesulfonamide;

N-(5-(tert-butyl)-3-(3-(4-((2-((3-(difluoromethoxy)-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxyphenyl)-methanesulfonamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-morpholinoethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)-methanesulfonamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-N,N-dimethylbenzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzoic acid;

1-(5-(tert-butyl)-3-cyano-2-methoxyphenyl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxy-ethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

3-(tert-butyl)-5-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)-amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-N-methylbenzamide;

N-(3-(tert-butyl)-5-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)methanesulfonamide;

1-(3-amino-5-(tert-butyl)-2-methoxyphenyl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxy-ethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

3-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxybenzamido)ethoxy)ethoxy)-propanoic acid;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-morpholinoethyl)benzamide;

1-(5-(tert-butyl)-2-methoxy-3-(pyrimidin-2-ylamino)phenyl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-N-methylbenzamide;

3-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)propanoic acid;

3-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxyphenoxy)ethoxy)propanoic acid;

2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)-amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-N-methyl-5-morpholinobenzamide;

5-(tert-butyl)-N-cyclopropyl-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxy-ethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

5-(tert-butyl)-N-(2-hydroxyethyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxy-ethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-methoxyethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)methanesulfonamide;

methyl 2-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamido)acetate;

N-benzyl-5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

5-(tert-butyl)-3-(3-(4-((2-((3-ethynyl-5-((2-morpholinoethyl)carbamoyl)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxy-N-methylbenzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-N-(2,5,8,11,14,17,20-heptaoxadocosan-22-yl)-5-methoxy-benzamide;

5-(tert-butyl)-N-ethyl-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

5-(tert-butyl)-N-isopropyl-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-N-(2-methoxyethyl)benzamide;

2-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzamido)acetic acid;

N-(3-(3-(4-((2-((3-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy)-5-methoxyphenyl)-amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-5-(tert-butyl)-2-methoxyphenyl)methane-sulfonamide;

5-(tert-butyl)-N-(2-(dimethylamino)ethyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-benzamide;

3-((4-((4-(3-(5-(tert-butyl)-3-carbamoyl-2-methoxyphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-morpholinoethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-3-carbamoyl-2-methoxyphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(2-morpholinoethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(2-morpholinoethyl)benzamide;

N-(5-(tert-butyl)-3-(3-(4-((2-((3-(cyclopropanecarbonyl)-5-methoxyphenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxyphenyl)methanesulfonamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-N-(oxetan-3-yl)-benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(2-(2-methoxyethoxy)ethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-3-carbamoyl-2-methoxyphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)benzenesulfonamide;

(R)-3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-ethynyl-N-(1-morpholinopropan-2-yl)benzamide;

(S)-3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-ethynyl-N-(1-morpholinopropan-2-yl)benzamide;

N-(5-(tert-butyl)-3-(3-(4-((2-((4-chloro-3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxyphenyl)-methanesulfonamide;

1-(5-(tert-butyl)-2-methoxy-3-(1,3,4-oxadiazol-2-yl)phenyl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

(S)-5-(tert-butyl)-3-(3-(4-((2-((3-ethynyl-5-((1-morpholinopropan-2-yl)carbamoyl)phenyl)-amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxy-N-methylbenzamide;

(R)-5-(tert-butyl)-3-(3-(4-((2-((3-ethynyl-5-((1-morpholinopropan-2-yl)carbamoyl)phenyl)-amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxy-N-methylbenzamide;

3-((4-((4-(3-(3-(tert-butyl)-5-carbamoylphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide;

1-(5-(tert-butyl)-2-oxo-2,3-dihydrobenzo[d]oxazol-7-yl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

1-(5-(tert-butyl)-2-methylbenzo[d]oxazol-7-yl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxy-ethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

3-((4-((4-(3-(3-(tert-butyl)-5-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(2-morpholinoethyl)benzamide;

(S)-3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(1-(2-(2-methoxyethoxy)ethoxy)propan-2-yl)benzamide;

(R)-3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynyl-N-(1-(2-(2-methoxyethoxy)ethoxy)propan-2-yl)benzamide;

N-(5-(tert-butyl)-2-ethoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)methanesulfonamide;

1-(5-(tert-butyl)-2-methoxy-3-(1H-1,2,3-triazol-5-yl)phenyl)-3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)urea;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)-1,1,1-trifluoro-methanesulfonamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)cyclohexane-sulfonamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)piperidine-1-sulfonamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)dimethylamino-sulfonamide;

5-(tert-butyl)-2-methoxy-N-(oxetan-3-yl)-3-(3-(4-((2-(phenylamino)pyridin-4-yl)oxy)-naphthalen-1-yl)ureido)benzamide;

5-(tert-butyl)-N-(2-(dimethylamino)ethyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-benzamide;

N-(4-(tert-butyl)-6-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)-amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-[1,1′-biphenyl]-2-yl)methanesulfonamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)morpholine-4-sulfonamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-N-(oxetan-3-yl)benzamide;

N-(5-(tert-butyl)-3-(3-(4-((2-((3-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)-5-methoxyphenyl)-amino)pyrimidin-4-yl)oxy)naphthalen-1-yl)ureido)-2-methoxyphenyl)methanesulfonamide;

5-(tert-butyl)-2-methoxy-N-(oxetan-3-yl)-3-(3-(4-((2-(phenylamino)pyrimidin-4-yl)oxy)-naphthalen-1-yl)ureido)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-(pyrrolidin-1-yl)ethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-(piperidin-1-yl)ethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-(4-methylpiperazin-1-yl)ethyl)benzamide;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-(phenylamino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)morpholine-4-sulfonamide;

N-(2-aminoethyl)-5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide;

5-tert-butyl-2-methoxy-N-(oxetan-3-yl)-3-[[4-[[2-(2-pyridylmethylamino)-4-pyridyl]oxy]-1-naphthyl]carbamoylamino]benzamide;

5-tert-butyl-2-methoxy-3-[[4-[[2-(3-methoxyanilino)-4-pyridyl]oxy]-1-naphthyl]-carbamoylamino]-N-(oxetan-3-yl)benzamide; 3-[[4-[(2-anilino-4-pyridyl)oxy]-2,3-difluorophenyl]carbamoylamino]-5-tert-butyl-2-methoxy-N-(oxetan-3-yl)benzamide;

3-[[4-[(2-anilino-4-pyridyl)oxy]-1-naphthyl]carbamoylamino]-5-tert-butyl-2-methoxy-N-tetrahydropyran-4-yl-benzamide;

3-[[4-[(2-anilino-4-pyridyl)oxy]-1-naphthyl]carbamoylamino]-5-tert-butyl-2-methoxy-N-(1-methyl-4-piperidyl)benzamide;

3-[[4-[(2-anilino-4-pyridyl)oxy]-1-naphthyl]carbamoylamino]-5-tert-butyl-2-methoxy-N-[(3R)-tetrahydrofuran-3-yl]benzamide;

3-[[4-[(2-anilino-4-pyridyl)oxy]-1-naphthyl]carbamoylamino]-5-tert-butyl-2-methoxy-N-[(3S)-tetrahydrofuran-3-yl]benzamide;

1-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-[[2-[3-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]-5-methoxy-anilino]-4-pyridyl]oxy]-1-naphthyl]urea;

1-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-[[2-[3-(hydroxymethyl)-5-methoxyanilino]-4-pyridyl]oxy]-1-naphthyl]urea;

5-tert-butyl-3-[[4-[[2-[3-(hydroxymethyl)-5-methoxyanilino]-4-pyridyl]oxy]-1-naphthyl]carbamoylamino]-2-methoxybenzamide;

5-tert-butyl-3-[[4-[[2-[3-(hydroxymethyl)-5-methoxyanilino]-4-pyridyl]oxy]-1-naphthyl]carbamoylamino]-2-methoxy-N-methyl-benzamide;

3-[[4-[[4-[[5-tert-Butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-(2-morpholino-2-oxo-ethyl)benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(hydroxymethyl)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]-oxy]-2-pyridyl]amino]-5-ethynyl-N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-ethynyl-N-[2-(4-methylpiperazin-1-yl)ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-ethynyl-N-(3-morpholinopropyl)benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]pyrimidin-2-yl]amino]-5-methoxy-N-[2-(4-methylpiperazin-1-yl)ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]pyrimidin-2-yl]amino]-5-methoxy-N-(3-morpholinopropyl)benzamide;

5-tert-butyl-3-[[4-[2-[3-ethynyl-5-(2-morpholinoethylcarbamoyl)anilino]pyrimidin-4-yl]oxy-1-naphthyl]carbamoylamino]-2-methoxy-benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-(2-methyl-2-morpholino-propyl)benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-(2-thiomorpholinoethyl)benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-[2-(1-oxo-1,4-thiazinan-4-yl)ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-N-[2-(1,1-dioxo-1,4-thiazinan-4-yl)ethyl]-5-methoxybenzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-N-[2-(3,3-dimethylmorpholin-4-yl)ethyl]-5-methoxybenzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-N-[2-(2,2-dimethylmorpholin-4-yl)ethyl]-5-methoxybenzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-N-[2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]ethyl]-5-methoxy-benzamide;

5-tert-butyl-3-[[4-[[2-[3-ethynyl-5-(hydroxymethyl)anilino]-4-pyridyl]oxy]-1-naphthyl]carbamoylamino]-2-methoxybenzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-[2-(4-methyl-1,4-diazepan-1-yl)ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-(2-piperazin-1-ylethyl)benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-N-[2-[2-(2-hydroxyethoxy)ethoxy]ethyl]-5-methoxybenzamide;

3-[[[4-[[4-[[5-tert-Butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]pyrimidin-2-yl]amino]methyl]-N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]benzamide;

3-[[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]pyrimidin-2-yl]amino]methyl]-N-(2-morpholinoethyl)benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-[2-(2-methoxyethoxy)ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethyl]-benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-N-[2-(4-hydroxy-1-piperidyl)ethyl]-5-methoxybenzamide;

1-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-[2-[3-methoxy-5-[2-[2-(2-methoxyethoxy)ethoxy]ethylsulfinyl]anilino]pyridin-4-yl]oxy-1-naphthyl]urea;

1-[5-tert-Butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-[2-[3-methoxy-5-[2-[2-(2-methoxyethoxy)ethoxy]ethylsulfonyl]anilino]pyridin-4-yl]oxy-1-naphthyl]urea;

5-tert-butyl-3-[[4-[[2-[3-(hydroxymethyl)-5-methoxyanilino]-4-pyridyl]oxy]-1-naphthyl]-carbamoylamino]-2-methoxy-N-(oxetan-3-yl)benzamide;

3-[[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]pyrimidin-2-yl]amino]methyl]-5-methoxy-N-[2-[2-(2-methoxyethoxy)ethoxy]-ethyl]benzamide;

3-[[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]pyrimidin-2-yl]amino]methyl]-5-methoxy-N-(2-morpholinoethyl)benzamide;

1-[5-tert-butyl-3-(cyanomethyl)-2-methoxyphenyl]-3-[4-[[2-[3-methoxy-5-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]anilino]-4-pyridyl]oxy]-1-naphthyl]urea;

3-[[4-[[4-[[5-tert-butyl-3-(cyanomethyl)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-(2-morpholinoethyl)benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(cyanomethyl)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-ethynyl-N-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-[2-(1,4-oxazepan-4-yl)ethyl]benzamide;

3-[[4-[[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]-1-naphthyl]oxy]-2-pyridyl]amino]-5-methoxy-N-[2-(4-oxo-1-piperidyl)ethyl]benzamide; and

5-tert-butyl-3-[[4-[[2-[3-ethynyl-5-(hydroxymethyl)anilino]-4-pyridyl]oxy]-1-naphthyl]carbamoylamino]-2-methoxy-N-methyl-benzamide,

and a pharmaceutically acceptable salt thereof.

18. A compound as claimed in claim 1 which is a compound selected from the group consisting of:

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-morpholinoethyl)benzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-N-methylbenzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide; and

5-(tert-butyl)-2-methoxy-N-(oxetan-3-yl)-3-(3-(4-((2-(phenylamino)pyridin-4-yl)oxy)-naphthalen-1-yl)ureido)benzamide,

and a pharmaceutically acceptable salt thereof.

19. A compound as claimed in claim 1 , wherein the compound is not:

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide;

3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxy-N-(2-morpholinoethyl)benzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy)-ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-N-methylbenzamide;

5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-(2-methoxyethoxy)ethoxy) ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)benzamide; and/or

5-(tert-butyl)-2-methoxy-N-(oxetan-3-yl)-3-(3-(4-((2-(phenylamino)pyridin-4-yl)oxy)-naphthalen-1-yl)ureido)benzamide,

or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical formulation comprising a compound as defined in claim 1 , or pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.

21. A combination product comprising

(A) a compound as defined in claim 1 , or pharmaceutically acceptable salt thereof, and

(B) another therapeutic agent,

wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.

22. A process for the preparation of a compound according to claim 1 which process comprises:

(a) reaction of a compound of formula II,

with a compound of formula III,

wherein one of Z 1 and Z 2 is a structural fragment of formula IV

and the other of Z 1 and Z 2 is a structural fragment of formula V

where R 1A to R 1E , R 2 to R 5 , L and X 1 to X 3 are as defined in any one of claims 1 to 21 ;

(b) reaction of a compound of formula IIa,

wherein Z 1 is as defined above, with a suitable azide-forming agent,

which reaction is followed, without isolation, by thermal rearrangement of the intermediate acyl azide (of formula Z 1 —C(O)—N 3 ) to provide, in situ, a compound of formula II, which compound is then reacted with a compound of formula III as defined above;

(c) reaction of a compound of formula IIb,

wherein LG 1 represents a leaving group and Z 1 is as defined above, with a compound of formula III, as defined above;

(d) reaction of a compound of formula VI,

wherein LG 2 represents a leaving group and R 1A to R 1E , R 2 , R 3 and X 1 are as defined in any one of claims 1 to 18 , with a compound of formula VII,

wherein R 4 , R 5 , L, X 2 and X 3 are as defined in claim 1 ;

(e) for compounds of formula I in which R 4 represents

—S(O) 1-2 —[C(R 6c )(R 6d )—(CH 2 ) 0-1 CH 2 —O] 1-12 —CH 2 (CH 2 ) 0-1 CH 2 —R 6a ,

—S(O) 1-2 —C(R 6c )(R 6d )—[C 1-5 alkylene]-R 6a ,

—S(O) 1-2 R 6b ,

oxidation of a corresponding compound of formula I in which, respectively, R 4 represents

—S—[CH 2 (CH 2 ) 0-1 CH 2 —O] 1-12 —CH 2 (CH 2 ) 0-1 CH 2 —R 6a ,

—S—CH 2 —[C 1-5 alkylene]-R 6a ,

—S—R 6b ,

wherein R 6a to R 6d are as defined in claim 1 ;

(f) for compounds of formula I in which R 4 represents

—C(O)NH—[C(R 6c )(R 6d )—(CH 2 ) 0-1 CH 2 —O] 1-12 —CH 2 (CH 2 ) 0-1 CH 2 —R 6a or

—C(O)NH—C(R 6c )(R 6d )—[C 1-5 alkylene]-R 6a ,

reaction of a compound of formula VIIa,

wherein R 4′ represents H or a C 1-3 alkyl group and R 1A to R 1E , R 2 , R 3 , R 5 , L and X 1 to X 3 are as defined in claim 1 , with a compound of formula VIIb or VIII,

H 2 N—[C(R 6c )(R 6d )—(CH 2 ) 0-1 CH 2 —O] 1-12 —CH 2 (CH 2 ) 0-1 CH 2 —R 6a VIIb

H 2 N—C(R 6c )(R 6d )—[C 1-5 alkylene]-R 6a or VIIc

wherein R 6a , R bc and R 6d are as defined in claim 1 ;

(g) for compounds of formula I in which R 1 represents —C(O)NR X R Y , reaction of a compound of formula VIId,

wherein R 1A , R 1C , R 1D , R 1E , R a , R b , X 1 to X 3 , L, R 4 and R 5 are as defined in claim 1 and R X represents H or C 1-4 alkyl, with a compound of formula VIIe,

R X and R Y are as defined in claim 1 ; or

(h) deprotection of an protected derivative of a compound of formula I, wherein the protected derivative bears a protecting group on an 0- or N-atom of the compound of formula I.

23. A method of treating an inflammatory disease, said method comprising administering to a subject an effective amount of a compound as defined in claim 1 , or pharmaceutically acceptable salt thereof, wherein the inflammatory disease is uveitis, Crohn's disease, ulcerative colitis, asthma, COPD or keratoconjunctivitis sicca (dry eye).

24. The method of claim 23 , wherein said uveitis is selected from the group consisting of posterior uveitis, anterior uveitis and pan uveitis.