Claims for Patent: 7,803,839

Summary for Patent: 7,803,839

Title:	Azetidines as MEK inhibitors for the treatment of proliferative diseases
Abstract:	Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof. Such compounds are MEK inhibitors and are useful in the treatment of proliferative diseases, such as cancer. Also disclosed are pharmaceutical compositions containing such compounds as well as methods of using the compounds and compositions of the invention in the treatment of cancer.
Inventor(s):	Naing Aay, Neel Kumar Anand, Charles M. Blazey, Owen Joseph Bowles, Joerg Bussenius, Simona Costanzo, Jeffry Kimo Curtis, Steven Charles Defina, Larisa Dubenko, Anagha Abhijit Joshi, Abigail R. Kennedy, Angie Inyoung Kim, Elena S. Koltun, Jean-Claire Limun Manalo, Csaba J. Peto, Kenneth D. Rice, Tsze H. Tsang
Assignee:	Exelixis Inc
Application Number:	US11/995,928
Patent Claims:	1. A compound of formula I: or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt, thereof, wherein A, X, R1, R2, R3, R4, R5, R6, and R7 are as defined in Group A, Group B, Group C, or Group D: Group A: A is phenylene optionally substituted with one, two, three or four groups selected from R10, R12, R14, and R16 where R10, R12, R14 and R16 are independently hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkoxy, hydroxy, alkoxy, amino, alkylamino, dialkylamino, haloalkyl, —NHS(O)2R8, —CN, —C(O)R8, —C(O)OR8, —C(O)NR8R8′ and NR8C(O)R8′; X is alkyl, halo, haloalkyl, or haloalkoxy; R1, R2, R3, R4, R5 and R6 are independently hydrogen, halo, nitro, —NR8R8′, —OR8, —NHS(O)2R8, —CN, —S(O)mR8, —S(O)2NR8R8′, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′, —NR8C(O)R8′e, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25C(NR25aR25b)═CH(NO2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl; where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, —OR8, —NR8R8′, —NR8S(O)2R9, —CN, —S(O)mR9, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′ and —NR8C(O)R8′; or one of R1 and R2 together with the carbon to which they are attached, R3 and R4 together with the carbon to which they are attached, and R5 and R6 together with the carbon to which they are attached form C(O) or C(═NOH); m is 0, 1, or 2; R7 is hydrogen, halo or alkyl; R8, R8′ and R8″ are independently selected from hydrogen, hydroxy, optionally substituted alkoxy, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl; where the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two three, four, or five groups independently selected from alkyl, halo, hydroxy, hydroxyalkyl, optionally substituted alkoxy, alkoxyalkyl, haloalkyl, carboxy, alkoxycarbonyl, alkenyloxycarbonyl, optionally substituted cycloalkyl, optionally substituted cycloalkyloxycarbonyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted aryloxycarbonyl, optionally substituted arylalkyl, optionally substituted arylalkyloxy, optionally substituted arylalkyloxycarbonyl, nitro, cyano, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, —S(O)nR31 (where n is 0, 1, or 2 and R31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —NR34SO2R34a (where R34 is hydrogen or alkyl and R34a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl), —SO2NR35R35a (where R35 is hydrogen or alkyl and R35a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl), —NR32C(O)R32a (where R32 is hydrogen or alkyl and R32a is alkyl, alkenyl, alkoxy, or cycloalkyl), —NR30R30′ (where R30 and R30′ are independently hydrogen, alkyl, or hydroxyalkyl), and —C(O)NR33R33a (where R33 is hydrogen or alkyl and R33a is alkyl, alkenyl, alkynyl, or cycloalkyl); and R9 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl; where the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, or five groups selected from halo, hydroxy, alkyl, haloalkyl, haloalkoxy, amino, alkylamino, and dialkylamino; R25 and R25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R25′ is hydrogen, alkyl, or alkenyl. 2. The Compound of claim 1 selected from Group A where A is phenylene optionally substituted with one or two groups selected from R10, R12, R14, and R16 where R10, R12, R14 and R16 are independently hydrogen or halo; X is halo; R1, R2, R5 and R6 are hydrogen; R3 is hydrogen, halo, hydroxy, alkoxy, or amino; R4 is hydrogen, —NR8R8′, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25C(NR25aR25b)═CH(NO2), alkyl, alkenyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three groups independently selected from —OR8, halo, nitro, —S(O)mR9, optionally substituted heterocycloalkyl, —NR8R8′, —NR8C(O)R8′, —NR8S(O)2R9, —NR8C(O)OR8′, and aryl; where the cycloalkyl is optionally substituted with one or two groups selected from —OR8 and —NR8R8′; where the heterocycloalkyl is optionally substituted with one or two groups independently selected from alkyl and —C(O)OR8; and where the heteroaryl is optionally substituted with —NR8R8′; or R3 and R4 together with the carbon to which they are attached form C(O) or C(═NOH); m is 0; R7 is halo; R8 and R8′ are independently selected from hydrogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heterocycloalkyl, heteroaryl, and cycloalkyl; where the R8 and R8′ alkyl are independently optionally substituted with one, two, or three groups independently selected from hydroxy, —NR30R30′ (where R30 and R30′ are independently hydrogen, alkyl, or hydroxyalkyl), optionally substituted heteroaryl, optionally substituted cycloalkyl), optionally substituted alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, —C(O)NR33R33a (where R33 is hydrogen or alkyl and R33a is alkyl, alkenyl, alkynyl, or cycloalkyl), optionally substituted aryloxy, —S(O)nR31 (where n is 0 and R31 is alkyl), carboxy, alkoxycarbonyl, and —NR32C(O)R32a (where R32 is hydrogen or alkyl and R32a is alkyl, alkenyl, alkoxy, or cycloalkyl); or where the alkyl is optionally substituted with one, two, three, four, or five halo; where the R8 and R8′ heteroaryl are independently optionally substituted with one or two groups independently selected from amino and alkyl; where the R8 and R8′ heterocycloalkyl are independently optionally substituted with one, two, or three groups independently selected from alkyl, alkoxycarbonyl, optionally substituted arylalkyl, hydroxy, alkoxy, and hydroxyalkyl; where the R8 and R8′ aryl are independently optionally substituted with one or two groups independently selected from hydroxy, alkoxy, halo, —NR32C(O)R32a (where R32 is hydrogen or alkyl and R32a is alkyl, alkenyl, alkoxy, or cycloalkyl), and —NR34SO2R34a (where R34 is hydrogen or alkyl and R34a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl); and where the R8 and R8′ cycloalkyl are independently optionally substituted with one, two, or three groups independently selected from hydroxy, hydroxyalkyl, alkoxy, carboxy, —C(O)NR33R33a (where R33 is hydrogen or alkyl and R33a is alkyl, alkenyl, alkynyl, or cycloalkyl), and optionally substituted cycloalkyl; and R9 is alkyl or aryl; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt or solvate thereof. 3. The compound of claim 1 where R3 is halo, nitro, —NR8R8′, —OR8, —NHS(O)2R8, —CN, —S(O)mR8, —S(O)2NR8R8′, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)NR8′R8, —NR8C(O)OR8′, —NR8C(O)R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25C(NR25aR25b)═CH(NO2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl; where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —OR8, —NR8R8′, —NR8S(O)2R9, —CN, —S(O)mR9, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′ and —NR8C(O)R8′; and R4 is as defined in claim 1; or R3 and R4 together with the carbon to which they are attached form C(O) or C(═NOH); or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 4. The compound of claim 1 where R3 and R4 are independently halo, nitro, —NR8R8′, —OR8, —NHS(O)2R8, —CN, —S(O)mR8, —S(O)2NR8R8′, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′, —NR8C(O)R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25C(NR25aR25b)═CH(NO2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl; where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —OR8, —NR8R8′, —NR8S(O)2R9, —CN, —S(O)mR9, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)NR8′R8′, —NR8C(O)OR8′ and —NR8C(O)R8′; or R3 and R4 together with the carbon to which they are attached form C(O) or C(═NOH); or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 5. The compound according to claim 1 wherein R7 is halo; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 6. The compound according to claim 1 wherein X is halo; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 7. The compound according to claim 1 wherein R1, R2, R5, and R6 are hydrogen; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 8. The compound of claim 1 where R4 is —NR8R8′ (where R8 is hydrogen, hydroxy, alkyl, alkoxy, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl and R8′ is hydroxy, alkoxy, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl), —NHS(O)2R8, —CN, —S(O)mR8, —S(O)2NR8R8′, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′, —NR8C(O)R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25C(NR25aR25b)═CH(NO2), alkenyl, or alkynyl; where the alkenyl and alkynyl are optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —OR8, —NR8R8′, —NR8S(O)2R9, —CN, —S(O)mR9, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′ and —NR8C(O)R8′; or R3 and R4 together with the carbon to which they are attached form C(O) or C(═NOH); or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 9. The compound of claim 1 where R3 is hydrogen, halo, hydroxy, amino, or alkoxy; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 10. The compound of claim 1 where R4 is hydrogen, —NR8R8′, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25C(NR25aR25b)═CH(NO2), alkyl, alkenyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three —OR8, halo, nitro, —S(O)mR9, optionally substituted heterocycloalkyl, —NR8R8′, —NR8C(O)R8′, —NR8S(O)2R9, —NR8C(O)OR8′, aryl; where the cycloalkyl is optionally substituted with one or two —NR8R8′; where the heterocycloalkyl is optionally substituted with one or two groups independently selected from alkyl and —C(O)OR8; and where the heteroaryl is optionally substituted with —NR8R8′; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 11. The compound of claim 1 where A is phenylene optionally substituted with one or two groups independently selected from R10, R12, R14, and R16 where R10, R12, R14 and R16 are independently hydrogen or halo; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 12. The compound of claim 1 where R3 is hydrogen; and R4 is hydrogen, —NR8R8′, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)R8′, alkyl, or heterocycloalkyl; where the alkyl is optionally substituted with one or two groups independently selected from —OR8 and —NR8R8′; and where the heterocycloalkyl is optionally substituted with —NR8R8′; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 13. The compound of claim 1 where R3 is alkoxy; and R4 is alkyl or heterocycloalkyl where the alkyl is substituted with —NR8R8; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 14. The compound of claim 1 where R3 is halo; and R4 is alkyl or heterocycloalkyl where the alkyl is substituted with —NR8R8′; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 15. The compound of claim 1 where and R3 and R4 together with the carbon to which they are attached form C(O) or C(═NOH); or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 16. The compound of claim 1 where R3 is hydroxy; and R4 is hydrogen, —C(O)NR8R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25c(NR25aR25b)═CH(NO2), alkyl, alkenyl, heterocycloalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three groups selected from —OR8, halo, nitro, —S(O)mR9, optionally substituted heterocycloalkyl, —NR8R8′, —NR8C(O)R8′, optionally substituted heteroaryl, —NR8S(O)2R9, —NR8C(O)OR8′, and aryl; where the cycloalkyl is optionally substituted with one or two groups independently selected from —NR8R8′ and —C(O)NR33R33a; where the heterocycloalkyl is optionally substituted with one, two or three groups independently selected from alkyl and —C(O)OR8; and where the heteroaryl is optionally substituted with —NR8R8′; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 17. The compound of claim 1 where R7 is iodo or bromo; X is fluoro or chloro; and R1, R2, R5, and R6 are hydrogen; and R10, R12, R14, and R16 are independently hydrogen or fluoro; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 18. The compound of claim 17 where R10 is 3-fluoro and R12, R14, and R16 are hydrogen or halo; R10 is 3-fluoro, R12 is 4-fluoro, and R14 and R16 are hydrogen; R10 is 4-fluoro, R12 is 5-fluoro, and R14 and R16 are hydrogen; R10 is 4-fluoro, R12 is 6-fluoro, and R14 and R16 are hydrogen; or R12 is 4-fluoro and R10, R14, and R16 are hydrogen; or a single stereoisomer or mixture of stereoisomers hereof and optionally as a pharmaceutically acceptable salt thereof. 19. The Compound of claim 1 where R3 is hydroxy; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 20. The Compound of claim 19 where R4 is —C(O)NR8R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), —CH2NR25C(NR25aR25b)═CH(NO2), alkyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl, cycloalkyl, heteroaryl, and heterocycloalkyl are independently optionally substituted with one, two, three, or four groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —OR8, —NR8R8, —NR8S(O)2R9, —CN, —S(O)mR9, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′ and —NR8C(O)R8′; or where the alkyl is optionally substituted with one, two, three, four, five, six or seven halo; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 21. The Compound of claim 20 where R4 is alkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with —NR8R8′; where the heterocycloalkyl is optionally substituted with alkyl or —C(O)OR8; and where the heteroaryl is optionally substituted with alkyl; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 22. The Compound of claim 1 where R1 is halo, nitro, —NR8R8′, —OR8, —NHS(O)2R8, —CN, —S(O)mR8, —S(O)2NR8R8, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)OR8′, —NR8C(O)NR8′R8″, —NR8C(O)OR8′, —NR8C(O)R8′, —CH2N(R25)(NR25aR25b), —CH2NR25C(═NH)(NR25aR25b), —CH2NR25C(═NH)(N(R25a)(NO2)), —CH2NR25C(═NH)(N(R25a)(CN)), —CH2NR25C(═NH)(R25), or —CH2NR25C(NR25aR25b)═CH(NO2), alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl; where the alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, or heterocycloalkyl are independently optionally substituted with one, two, three, four, five, six or seven groups independently selected from halo, alkyl, haloalkyl, nitro, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, —OR8, —NR8R8′, —NR8S(O)2R9, —CN, —S(O)mR9, —C(O)R8, —C(O)OR8, —C(O)NR8R8′, —NR8C(O)NR8′R8′, —NR8C(O)OR8′ and —NR8C(O)R8′; R3 is hydroxy; and R4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR8R8′ and where the heteroaryl is optionally substituted with alkyl; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 23. The compound according to claim 1 selected from the group consisting of: 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}-carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-one; 6-(azetidin-1-ylcarbonyl)-2,3-difluoro-N-(2-fluoro-4-iodophenyl)aniline; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- (hydroxymethyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- (trifluoromethyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-prop-2-en-1-ylazetidin- 3-ol; 3-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]propane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-ethylazetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-methylazetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-ethenylazetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-one; oxime; [1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]methanol; 1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]ethane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-hydroxyazetidine-3- carboxamide; 1,1-dimethylethyl [1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]carbamate; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(pyrrolidin-1- ylmethyl)azetidin-3-ol; 3-[(diethylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(dimethylamino)methyl]azetidin-3-ol; N-butyl-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidine-3- carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-prop-2-en-1- ylazetidine-3-carboxamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-2- methylpropanamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3- yl]formamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-3,4- dihydroxybutanamide; methyl [1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3- yl]carbamate; N-butyl-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2- yl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2R)-piperidin-2- yl]azetidin-3-ol; (R)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2- ylazetidin-3-ol; (S)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2- ylazetidin-3-ol; 3-(aminomethyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin- 3-ol; 3-[(1S)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-[(1R)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; (R)-(3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4- iodophenylamino)phenyl)methanone; (S)-(3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4- iodophenylamino)phenyl)methanone; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-ethylazetidine-3- carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2- hydroxyethyl)azetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2-piperidin-1- ylethyl)azetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-phenylazetidine-3- carboxamide; N-[2-(diethylamino)ethyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(morpholin-4- ylmethyl)azetidin-3-ol; 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}piperidin-4-ol; 3-{[bis(2-hydroxyethyl)amino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-2-(4- methylpiperazin-1-yl)acetamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(4-methylpiperazin-1- yl)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(4-methyl-1,4- diazepan-1-yl)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[methyl(1- methylpyrrolidin-3-yl)amino]methyl}azetidin-3-ol; 3-(1,4′-bipiperidin-1′-ylmethyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-N,N- bis(2-hydroxyethyl)glycinamide; 3-({4-[2-(diethylamino)ethyl]piperazin-1-yl}methyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- hydroxyethyl)(methyl)amino]methyl}azetidin-3-ol; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-2- piperidin-1-ylacetamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-N3-(2- hydroxyethyl)-N3-methyl-beta-alaninamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-N3,N3- bis(2-hydroxyethyl)-beta-alaninamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-N2,N2- diethylglycinamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-methylazetidin-3- amine; 1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-N,N- dimethylpyrrolidin-3-amine; 2-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3- yl]amino}ethanol; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]propane- 1,3-diamine; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-methyl-N-(2-pyridin-2- ylethyl)azetidin-3-amine; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-N2- methylglycinamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-ethylazetidin-3-amine; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2- methylpropyl)azetidin-3-amine; N-(cyclopropylmethyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine; N-(cyclohexylmethyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine; N-(cyclopentylmethyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine; 3-(azetidin-1-ylmethyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-[(2,3- dihydroxypropyl)oxy]azetidine-3-carboxamide; 2-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-2- yl]methyl}amino)ethanol; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-2- yl]methyl}ethane-1,2-diamine; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3- yl]glycinamide; 6-({3-[(dimethylamino)methyl]azetidin-1-yl}carbonyl)-2,3-difluoro-N-(2-fluoro-4- iodophenyl)aniline; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1- methylethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(3,4- dihydroxybutyl)azetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2,3- dihydroxypropyl)azetidine-3-carboxamide; 1-({2,4-difluoro-6-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine; 1-({4,5-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-amine; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3- carboxamide; 6-{[3-(aminomethyl)-3-(methyloxy)azetidin-1-yl]carbonyl}-2,3-difluoro-N-(2-fluoro-4- iodophenyl)aniline; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}acetamide; 2,3-difluoro-N-(2-fluoro-4-iodophenyl)-6-[(3-{[(1-methylethyl)amino]methyl}azetidin-1- yl)carbonyl]aniline; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(ethylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{2-[(1- methylethyl)amino]ethyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(2-hydroxy-1,1- dimethylethyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{1,1-dimethyl-2-[(1- methylethyl)amino]ethyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1- methylethyl)amino]methyl}azetidin-3-amine; 3-[(cyclopropylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2,2,2- trifluoroethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1H-imidazol-1- ylmethyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1,1- dimethylethyl)amino]methyl}azetidin-3-ol; 3-[(cyclopentylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxy-N-prop-2-en- 1-ylazetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2,3-dihydroxypropyl)- 3-hydroxyazetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1H-1,2,3-triazol-1- ylmethyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2,2- dimethylpropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(propylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- methylpropyl)amino]methyl}azetidin-3-ol; 3-{[(cyclopropylmethyl)amino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- {[(phenylmethyl)amino]methyl}azetidin-3-ol; 3-{[(cyclohexylmethyl)amino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-[(butylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(1-ethylpyrrolidin-2- yl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- hydroxyethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2- (dimethylamino)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2-hydroxy-1,1- dimethylethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2-(4- methylphenyl)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(prop-2-en-1- ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2-(1- methylpyrrolidin-2-yl)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2,3-dihydro-1H- inden-2-ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(tetrahydrofuran-2- ylmethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2-(tetrahydro-2H- pyran-4-yl)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(1S,2S)-2- hydroxycyclopentyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1,1-dimethylprop-2- yn-1-yl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3-pyrrolidin-1- ylpropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1,2- dimethylpropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2-(1H-imidazol-4- yl)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[1-methyl-2- (methyloxy)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[3- (ethyloxy)propyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1- ethylpropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3,3- dimethylbutyl)amino]methyl}azetidin-3-ol; ethyl 4-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}amino)piperidine-1-carboxylate; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[3- (methylthio)propyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2- (ethyloxy)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[3- (dimethylamino)propyl]amino}methyl)azetidin-3-ol; 3-[(cyclobutylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino] phenyl}carbonyl)azetidin-3-ol; 3-({[3-(diethylamino)propyl]amino}methyl)-1-({3,4-difluoro-2-[(2-fluoro- 4-iodophenyl(amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[3- (1H-imidazol-1-yl)propyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2- (methylthio)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[1- (phenylmethyl)piperidin-4-yl]amino}methyl)azetidin-3-ol; 3-({[2,2-bis(methyloxy)ethyl]amino}methyl-1-({3,4-difuro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[1,1,3,3- tetramethylbutyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[1,1- (dimethylpropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2,3- (dihydro-1H-iden-1-)ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2- (phenylmethyl)oxyl]cyclopentyl}amino)amethyl]azetidin-3-ol; 3-{[(3-amino-2-hydroxypropyl)amino]methyl}-1-({3,4-difluoro-2-[(2- fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- ({[2-hydroxy-1-(phenylmethyl)ethyl]amino}methyl)azetidin-3-ol; 3-[(cyclooctylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-{[(1-cyclohexylethyl)amino]methyl}-1-({3,4-difluro-2-[(2- fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-[(cycloheptylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- {[(2-pyridin-3-ylethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- ({[(methylthio)propyl]amino}methyl)azetidin-3-ol; N-cyclohexyl-N2-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}-2-methylalaninamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(tetrahydro-2H- pyran-4-ylmethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3- hydroxypropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2-pyridin-4- ylethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[1- (phenylmethyl)pyrrolidin-3-yl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2-(2- thienyl)ethyl]amino}methyl)azetidin-3-ol; 3-[({2-[bis(1-methylethyl)amino]ethyl}amino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2- (phenyloxy)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(phenylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- hydroxypropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[({2-[(1- methylethyl)oxy]ethyl}amino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1-ethylpiperidin-3- yl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2- (methyloxy)ethyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-nitropropyl)azetidin- 3-ol; 3-(1-aminoethyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin- 3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(1-methylpiperidin- 4-yl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[4- (dimethylamino)butyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2-furan-2- ylethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{1-[(1,1- dimethylethyl)amino]ethyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- ethylbutyl)amino]methyl}azetidin-3-ol; 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}pyrrolidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({(2S)-2- [(methyloxy)methyl]pyrrolidin-1-yl}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- hydroxyphenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(4- hydroxyphenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3- hydroxyphenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(phenyloxy)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1r,3r,5R,7R)- tricyclo[3.3.1.13,7]dec-2-ylamino]methyl}azetidin-3-ol; 3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin- 3-yl]methyl}amino)propane-1,2-diol; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}-L-alanine; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(phenylthio)methyl]azetidin-3-ol; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}-D-alanine; methyl N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}alaninate; 3-[({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin- 3-yl]methyl}amino)oxy]propane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(5-methyl-1,3,4- oxadiazol-2-yl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1- methylbutyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1- methylpropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- methylbutyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(pentylamino)methyl]azetidin-3-ol; 3-[(cyclohexylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[1- (ethylamino)ethyl]azetidin-3-ol; 3-[(azepan-3-ylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2-(dimethylamino)- 1-methylethyl]amino}methyl)azetidin-3-ol; N-cyclopropyl-1-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}amino)cyclopentanecarboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[2-(2,3-dihydro-1H- indol-3-yl)ethyl]amino}methyl)azetidin-3-ol; N2-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}-N-ethyl-2-methylalaninamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2- methylhydrazino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- [(hydroxyamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- {[(methyloxy)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- {[(ethyloxy)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[1- (ethylamino)propyl]azetidin-3-ol; 3-[(azetidin-3-ylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1,3-thiazol-2- ylamino)methyl]azetidin-3-ol; 1,1-dimethylethyl [3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)- 3-hydroxyazetidin-3-yl]methyl}amino)propyl]carbamate; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(pyrrolidin-2- ylmethyl)amino]methyl}azetidin-3-ol; 1,1-dimethylethyl 4-[({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)- 3-hydroxyazetidin-3-yl]methyl}amino)methyl]piperidine-1-carboxylate; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(2- hydroxyphenyl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(3- hydroxyphenyl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(4- hydroxyphenyl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(4- hydroxybutyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- hydroxyethyl)oxy]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(1S,2S)-2- hydroxycyclohexyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(1,1-dimethyl-2- pyrrolidin-1-ylethyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(1-methyl-1H- imidazol-4-yl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(1-methyl-1H- imidazol-5-yl)methyl]amino}methyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[(2S)-2- (methyloxy)cyclopentyl]amino}methyl)azetidin-3-ol; 3-{[1,1′-bi(cyclohexyl)-2-ylamino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[3- (methyloxy)phenyl]amino}methyl)azetidin-3-ol; 1-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin- 3-yl]methyl}amino)cyclopentanecarboxylic acid; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(4- fluorophenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1,3,5-triazin-2- ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(trans-4- hydroxycyclohexyl)amino]methyl}azetidin-3-ol; 3-[(cyclopent-3-en-1-ylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; N-[4-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}amino)phenyl]acetamide; N-[3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}amino)phenyl]acetamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-methylpyrrolidin-2- yl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1H-1,2,4-triazol-3- ylamino)methyl]azetidin-3-ol; 3-[1-(diethylamino)propyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin- 3-yl]methyl}amino)-5-(hydroxymethyl)cyclopentane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-piperidin-2-ylazetidin- 3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3- fluorophenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-methylpiperidin-2- yl)azetidin-3-ol; 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}guanidine; 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}-3-nitroguanidine; N-{1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin- 3-yl]ethyl}acetamide; (2R)-N-{1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]ethyl}-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(piperidin-4- ylmethyl)amino]methyl}azetidin-3-ol; 3-{[(3-aminopropyl)amino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[({[2-(4- methylpiperazin-1-yl)phenyl]methyl}amino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2- hydroxycyclohexyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2,2,3,3,3- pentafluoropropyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3,3,3- trifluoropropyl)amino]methyl}azetidin-3-ol; N-[3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}amino)phenyl]methanesulfonamide; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}methanesulfonamide; 3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin- 3-yl]methyl}amino)-1H-pyrazol-5-ol; (1R,2S)-4-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}amino)cyclopentane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- ({[1-(hydroxymethyl)cyclohexyl]amino}methyl)azetidin-3-ol; 3-{[(3-chlorophenyl)amino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-{[(4-chlorophenyl)amino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-[(5-amino-3-methyl-1H-pyrazol-1-yl)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(5-methyl-1H- pyrazol-3-yl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-ethylpyrrolidin-2- yl)azetidin-3-ol; (2R)-N-{(1S)-1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]ethyl}-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[4- (methyloxy)phenyl]amino}methyl)azetidin-3-ol; 3-(1-amino-2-methylpropyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-{[(4-aminophenyl)amino]methyl}-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2-hydroxy-2- methylcyclopentyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{1-[(4- hydroxycyclohexyl)amino]ethyl}azetidin-3-ol; methyl (2xi)-2-deoxy-2-({[1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]methyl}amino)-beta-D-arabino- hexopyranoside; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyridin-2-ylazetidin-3- ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-({[1- (hydroxymethyl)cyclopentyl]amino}methyl)azetidin-3-ol; 1-cyano-3-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}guanidine; 6-({3-[(ethylamino)methyl]-3-fluoroazetidin-1-yl}carbonyl)-2,3-difluoro-N-(2-fluoro-4- iodophenyl)aniline; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-nitroethyl)azetidin- 3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3-fluoro-4- hydroxyphenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2-fluoro-4- hydroxyphenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[1- (methylamino)ethyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1H-pyrrol-2- yl)azetidin-3-ol; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3- yl]methyl}benzenecarboximidamide; 3-({[(E)-1-amino-2-nitroethenyl]amino}methyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-methyl-1- nitroethyl)azetidin-3-ol; 3-(1-amino-1-methylethyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-[(1H-benzimidazol-2-ylamino)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1H-imidazol-2- ylamino)methyl]azetidin-3-ol; methyl {1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3- hydroxyazetidin-3-yl]ethyl}carbamate; 3-(1H-benzimidazol-2-yl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[1- (dimethylamino)ethyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(pyrimidin-2- ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(pyridin-2- ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-methyl-1H- imidazol-2-yl)azetidin-3-ol; 3-(1-aminobutyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-[amino(phenyl)methyl]-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(5-methyl-1H- imidazol-2-yl)azetidin-3-ol; 1,1-dimethylethyl (2S)-2-[1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]piperidine-1-carboxylate; 1-({2-[(4-bromo-2-chlorophenyl)amino]-3,4-difluorophenyl}carbonyl)-3-piperidin-2- ylazetidin-3-ol; 3-(1-amino-3-hydroxypropyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1H-imidazol-2- ylmethyl)azetidin-3-ol; 3-(1-aminocyclopentyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-(2-aminocyclohexyl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 3-(2-aminocyclopentyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)- azetidin-3-ol; 1-({2-[(4-bromo-2-fluorophenyl)amino]-3,4-difluorophenyl}carbonyl)-3-piperidin-2- ylazetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(3-methyl-1- nitrobutyl)azetidin-3-ol; 3-(2-aminopyrimidin-4-yl)-1-({3,4-difluoro-2-[(2-fluoro-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S,2S)-2- hydroxycyclohexyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S,2R)-2- hydroxycyclohexyl]azetidin-3-ol; 1-({3-fluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2- yl]azetidin-3-ol; 1-({4-fluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2- yl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(6-methylpiperidin-2- yl)azetidin-3-ol; and 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-piperazin-2-ylazetidin- 3-ol; (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(trans)- 2-hydroxycyclohexyl]azetiden-3-ol; (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(cis)- 2-hydroxycyclohexyl]azetiden-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S)- 1-(methylamino)ethyl]azetidin-3-ol; and a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof. 24. A pharmaceutical composition comprising a compound of claim 1 or a single stereoisomer or mixture of stereoisomers thereof, optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 25. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2-ylazetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 26. The Compound of claim 23 named (R)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2-ylazetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 27. The Compound of claim 23 named (S)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2-ylazetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 28. The Compound of claim 23 named (3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)methanone, optionally as a pharmaceutically acceptable salt thereof. 29. The Compound of claim 23 named (R)-(3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)methanone, optionally as a pharmaceutically acceptable salt thereof. 30. The Compound of claim 23 named (S)-(3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)methanone, optionally as a pharmaceutically acceptable salt thereof). 31. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[1-(methylamino)ethyl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 32. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S)-1-(methylamino)ethyl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 33. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[piperidin-2-yl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 34. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2R)-piperidin-2-yl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 35. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 36. The Compound of claim 23 named (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(cis)-2-hydroxycyclohexyl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 37. The Compound of claim 23 named (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(trans)-2-hydroxycyclohexyl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 38. The Compound of claim 23 named 3-(1-aminoethyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 39. The Compound of claim 23 named 3-[(1R)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 40. The Compound of claim 23 named 3-[(1S)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 41. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(pyrrolidin-1-ylmethyl)azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 42. The Compound of claim 23 named 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]methyl}piperidin-4-ol, optionally as a pharmaceutically acceptable salt thereof. 43. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-methylazetidin-3-amine, optionally as a pharmaceutically acceptable salt thereof. 44. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(methyloxy)amino]methyl}azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 45. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-methylpyrrolidin-2-yl)azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 46. The Compound of claim 23 named 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-piperazin-2-ylazetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof. 47. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2-ylazetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 48. A pharmaceutical composition comprising (R)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2-ylazetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 49. A pharmaceutical composition comprising (5)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyrrolidin-2-ylazetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 50. A pharmaceutical composition comprising (3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)methanone optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 51. A pharmaceutical composition comprising (R)-(3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)methanone optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 52. A pharmaceutical composition comprising (S)-(3-(1-aminopropyl)-3-hydroxyazetidin-1-yl)(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)methanone optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 53. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[1-(methylamino)ethyl]azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 54. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S)-1-(methylamino)ethyl] azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 55. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[piperidin-2-yl]azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 56. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2R)-piperidin-2-yl]azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 57. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 58. A pharmaceutical composition comprising (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(cis)-2-hydroxycyclohexyl]azetidin-3-ol, optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 59. A pharmaceutical composition comprising (±)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(trans)-2-hydroxycyclohexyl]azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 60. A pharmaceutical composition comprising 3-(1-aminoethyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 61. A pharmaceutical composition comprising 3-[(1R)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 62. A pharmaceutical composition comprising 3-[(1S)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 63. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(pyrrolidin-1-ylmethyl)azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 64. A pharmaceutical composition comprising 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]methyl}piperidin-4-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 65. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-methylazetidin-3-amine optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 66. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(methyloxy)amino]methyl}azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 67. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-methylpyrrolidin-2-yl)azetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. 68. A pharmaceutical composition comprising 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-piperazin-2-ylazetidin-3-ol optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent.