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Last Updated: March 29, 2024

Details for Patent: 7,803,839


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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): Aay; Naing (San Mateo, CA), Anand; Neel Kumar (Burlingame, CA), Blazey; Charles M. (San Francisco, CA), Bowles; Owen Joseph (Pacifica, CA), Bussenius; Joerg (Foster City, CA), Costanzo; Simona (Los Altos, CA), Curtis; Jeffry Kimo (San Anselmo, CA), DeFina; Steven Charles (Burlingame, CA), Dubenko; Larisa (San Francisco, CA), Joshi; Anagha Abhijit (Fremont, CA), Kennedy; Abigail R. (Oakland, CA), Kim; Angie Inyoung (San Mateo, CA), Koltun; Elena S. (Foster City, CA), Manalo; Jean-Claire Limun (Daly City, CA), Peto; Csaba J. (Alameda, CA), Rice; Kenneth D. (San Rafael, CA), Tsang; Tsze H. (El Cerrito, CA)
Assignee: Exelixis, Inc. (South San Francisco, CA)
Filing Date:Oct 05, 2006
Application Number:11/995,928
Claims:1. A compound of formula I: ##STR00472## or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt, thereof, wherein A, X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 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 R.sup.10, R.sup.12, R.sup.14, and R.sup.16 where R.sup.10, R.sup.12, R.sup.14 and R.sup.16 are independently hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkoxy, hydroxy, alkoxy, amino, alkylamino, dialkylamino, haloalkyl, --NHS(O).sub.2R.sup.8, --CN, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8' and NR.sup.8C(O)R.sup.8'; X is alkyl, halo, haloalkyl, or haloalkoxy; R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8'e, --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), 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, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; or one of R.sup.1 and R.sup.2 together with the carbon to which they are attached, R.sup.3 and R.sup.4 together with the carbon to which they are attached, and R.sup.5 and R.sup.6 together with the carbon to which they are attached form C(O) or C(.dbd.NOH); m is 0, 1, or 2; R.sup.7 is hydrogen, halo or alkyl; R.sup.8, R.sup.8' and R.sup.8'' 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).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.34SO.sub.2R.sup.34a (where R.sup.34 is hydrogen or alkyl and R.sup.34a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl), --SO.sub.2NR.sup.35R.sup.35a (where R.sup.35 is hydrogen or alkyl and R.sup.35a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl), --NR.sup.32C(O)R.sup.32a (where R.sup.32 is hydrogen or alkyl and R.sup.32a is alkyl, alkenyl, alkoxy, or cycloalkyl), --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NR.sup.33R.sup.33a (where R.sup.33 is hydrogen or alkyl and R.sup.33a is alkyl, alkenyl, alkynyl, or cycloalkyl); and R.sup.9 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; R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25' 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 R.sup.10, R.sup.12, R.sup.14, and R.sup.16 where R.sup.10, R.sup.12, R.sup.14 and R.sup.16 are independently hydrogen or halo; X is halo; R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are hydrogen; R.sup.3 is hydrogen, halo, hydroxy, alkoxy, or amino; R.sup.4 is hydrogen, --NR.sup.8R.sup.8', --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three groups independently selected from --OR.sup.8, halo, nitro, --S(O).sub.mR.sup.9, optionally substituted heterocycloalkyl, --NR.sup.8R.sup.8', --NR.sup.8C(O)R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --NR.sup.8C(O)OR.sup.8', and aryl; where the cycloalkyl is optionally substituted with one or two groups selected from --OR.sup.8 and --NR.sup.8R.sup.8'; where the heterocycloalkyl is optionally substituted with one or two groups independently selected from alkyl and --C(O)OR.sup.8; and where the heteroaryl is optionally substituted with --NR.sup.8R.sup.8'; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.NOH); m is 0; R.sup.7 is halo; R.sup.8 and R.sup.8' are independently selected from hydrogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heterocycloalkyl, heteroaryl, and cycloalkyl; where the R.sup.8 and R.sup.8' alkyl are independently optionally substituted with one, two, or three groups independently selected from hydroxy, --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' 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)NR.sup.33R.sup.33a (where R.sup.33 is hydrogen or alkyl and R.sup.33a is alkyl, alkenyl, alkynyl, or cycloalkyl), optionally substituted aryloxy, --S(O).sub.nR.sup.31 (where n is 0 and R.sup.31 is alkyl), carboxy, alkoxycarbonyl, and --NR.sup.32C(O)R.sup.32a (where R.sup.32 is hydrogen or alkyl and R.sup.32a is alkyl, alkenyl, alkoxy, or cycloalkyl); or where the alkyl is optionally substituted with one, two, three, four, or five halo; where the R.sup.8 and R.sup.8' heteroaryl are independently optionally substituted with one or two groups independently selected from amino and alkyl; where the R.sup.8 and R.sup.8' 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 R.sup.8 and R.sup.8' aryl are independently optionally substituted with one or two groups independently selected from hydroxy, alkoxy, halo, --NR.sup.32C(O)R.sup.32a (where R.sup.32 is hydrogen or alkyl and R.sup.32a is alkyl, alkenyl, alkoxy, or cycloalkyl), and --NR.sup.34SO.sub.2R.sup.34a (where R.sup.34 is hydrogen or alkyl and R.sup.34a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl); and where the R.sup.8 and R.sup.8' cycloalkyl are independently optionally substituted with one, two, or three groups independently selected from hydroxy, hydroxyalkyl, alkoxy, carboxy, --C(O)NR.sup.33R.sup.33a (where R.sup.33 is hydrogen or alkyl and R.sup.33a is alkyl, alkenyl, alkynyl, or cycloalkyl), and optionally substituted cycloalkyl; and R.sup.9 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 R.sup.3 is halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8, --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), 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, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; and R.sup.4 is as defined in claim 1; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.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 R.sup.3 and R.sup.4 are independently halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), 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, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.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 R.sup.7 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 R.sup.1, R.sup.2, R.sup.5, and R.sup.6 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 R.sup.4 is --NR.sup.8R.sup.8' (where R.sup.8 is hydrogen, hydroxy, alkyl, alkoxy, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl and R.sup.8' is hydroxy, alkoxy, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl), --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8', --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), 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, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.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 R.sup.3 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 R.sup.4 is hydrogen, --NR.sup.8R.sup.8', --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three --OR.sup.8, halo, nitro, --S(O).sub.mR.sup.9, optionally substituted heterocycloalkyl, --NR.sup.8R.sup.8', --NR.sup.8C(O)R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --NR.sup.8C(O)OR.sup.8', aryl; where the cycloalkyl is optionally substituted with one or two --NR.sup.8R.sup.8'; where the heterocycloalkyl is optionally substituted with one or two groups independently selected from alkyl and --C(O)OR.sup.8; and where the heteroaryl is optionally substituted with --NR.sup.8R.sup.8'; 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 R.sup.10, R.sup.12, R.sup.14, and R.sup.16 where R.sup.10, R.sup.12, R.sup.14 and R.sup.16 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 R.sup.3 is hydrogen; and R.sup.4 is hydrogen, --NR.sup.8R.sup.8', --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', alkyl, or heterocycloalkyl; where the alkyl is optionally substituted with one or two groups independently selected from --OR.sup.8 and --NR.sup.8R.sup.8'; and where the heterocycloalkyl is optionally substituted with --NR.sup.8R.sup.8'; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof.

13. The compound of claim 1 where R.sup.3 is alkoxy; and R.sup.4 is alkyl or heterocycloalkyl where the alkyl is substituted with --NR.sup.8R.sup.8; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 where R.sup.3 is halo; and R.sup.4 is alkyl or heterocycloalkyl where the alkyl is substituted with --NR.sup.8R.sup.8'; 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 R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.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 R.sup.3 is hydroxy; and R.sup.4 is hydrogen, --C(O)NR.sup.8R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25c(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), alkyl, alkenyl, heterocycloalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three groups selected from --OR.sup.8, halo, nitro, --S(O).sub.mR.sup.9, optionally substituted heterocycloalkyl, --NR.sup.8R.sup.8', --NR.sup.8C(O)R.sup.8', optionally substituted heteroaryl, --NR.sup.8S(O).sub.2R.sup.9, --NR.sup.8C(O)OR.sup.8', and aryl; where the cycloalkyl is optionally substituted with one or two groups independently selected from --NR.sup.8R.sup.8' and --C(O)NR.sup.33R.sup.33a; where the heterocycloalkyl is optionally substituted with one, two or three groups independently selected from alkyl and --C(O)OR.sup.8; and where the heteroaryl is optionally substituted with --NR.sup.8R.sup.8'; or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 where R.sup.7 is iodo or bromo; X is fluoro or chloro; and R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; and R.sup.10, R.sup.12, R.sup.14, and R.sup.16 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 R.sup.10 is 3-fluoro and R.sup.12, R.sup.14, and R.sup.16 are hydrogen or halo; R.sup.10 is 3-fluoro, R.sup.12 is 4-fluoro, and R.sup.14 and R.sup.16 are hydrogen; R.sup.10 is 4-fluoro, R.sup.12 is 5-fluoro, and R.sup.14 and R.sup.16 are hydrogen; R.sup.10 is 4-fluoro, R.sup.12 is 6-fluoro, and R.sup.14 and R.sup.16 are hydrogen; or R.sup.12 is 4-fluoro and R.sup.10, R.sup.14, and R.sup.16 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 R.sup.3 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 R.sup.4 is --C(O)NR.sup.8R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), 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, --OR.sup.8, --NR.sup.8R.sup.8, --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; 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 R.sup.4 is alkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with --NR.sup.8R.sup.8'; where the heterocycloalkyl is optionally substituted with alkyl or --C(O)OR.sup.8; 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 R.sup.1 is halo, nitro, --NR.sup.8R.sup.8', --OR.sup.8, --NHS(O).sub.2R.sup.8, --CN, --S(O).sub.mR.sup.8, --S(O).sub.2NR.sup.8R.sup.8, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8'', --NR.sup.8C(O)OR.sup.8', --NR.sup.8C(O)R.sup.8', --CH.sub.2N(R.sup.25)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(NR.sup.25aR.sup.25b), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(NO.sub.2)), --CH.sub.2NR.sup.25C(.dbd.NH)(N(R.sup.25a)(CN)), --CH.sub.2NR.sup.25C(.dbd.NH)(R.sup.25), or --CH.sub.2NR.sup.25C(NR.sup.25aR.sup.25b).dbd.CH(NO.sub.2), 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, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --S(O).sub.mR.sup.9, --C(O)R.sup.8, --C(O)OR.sup.8, --C(O)NR.sup.8R.sup.8', --NR.sup.8C(O)NR.sup.8'R.sup.8', --NR.sup.8C(O)OR.sup.8' and --NR.sup.8C(O)R.sup.8'; R.sup.3 is hydroxy; and R.sup.4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8' 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: TABLE-US-00008 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-hyd- roxyazetidin-3- yl]propane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-ethyla- zetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-methyl- azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-etheny- lazetidin-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-hyd- roxyazetidin-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-hydrox- yazetidine-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-(pyrro- lidin-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)a- zetidine-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)azetid- in-3-yl]-2- methylpropanamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-3- yl]formamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-3-yl]-3,4- dihydroxybutanamide; methyl [1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)a- zetidin-3- yl]carbamate; N-butyl-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)a- zetidin-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-py- rrolidin-2- ylazetidin-3-ol; (S)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-py- rrolidin-2- ylazetidin-3-ol; 3-(aminomethyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}ca- rbonyl)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-ethyla- zetidine-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-pip- eridin-1- ylethyl)azetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-phenyl- azetidine-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-(morph- olin-4- ylmethyl)azetidin-3-ol; 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hy- droxyazetidin-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)azetid- in-3-yl]-2-(4- methylpiperazin-1-yl)acetamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(4-me- thylpiperazin-1- yl)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(4-me- thyl-1,4- diazepan-1-yl)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[meth- yl(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)azetid- in-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)azetid- in-3-yl]-2- piperidin-1-ylacetamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-3-yl]-N3-(2- hydroxyethyl)-N3-methyl-beta-alaninamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-3-yl]-N3,N3- bis(2-hydroxyethyl)-beta-alaninamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-3-yl]-N2,N2- diethylglycinamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-methyl- azetidin-3- amine; 1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-3-yl]-N,N- dimethylpyrrolidin-3-amine; 2-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azeti- din-3- yl]amino}ethanol; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-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)azetid- in-3-yl]-N2- methylglycinamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-ethyla- zetidin-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)azet- idin-2- yl]methyl}amino)ethanol; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azeti- din-2- yl]methyl}ethane-1,2-diamine; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetid- in-3- yl]glycinamide; 6-({3-[(dimethylamino)methyl]azetidin-1-yl}carbonyl)-2,3-difluoro-N-(2-flu- oro-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-hydrox- yazetidine-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-hy- droxyazetidin-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-hyd- roxy-1,1- dimethylethyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{1,1-d- imethyl-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-im- idazol-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-hydrox- y-N-prop-2-en- 1-ylazetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2,3-d- ihydroxypropyl)- 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-h- ydroxy-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-{[(tet- rahydrofuran-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-p- yrrolidin-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-m- ethyl-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}carbony- l)-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)ami- no] 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-N.sup.2-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]ph- enyl}carbonyl)-3- hydroxyazetidin-3-yl]methyl}-2-methylalaninamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(tet- rahydro-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-p- yridin-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-e- thylpiperidin-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-nit- ropropyl)azetidin- 3-ol; 3-(1-aminoethyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}c- arbonyl)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-f- uran-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-hy- droxyazetidin-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[3.3.1.1.sup.3,7]dec-2-ylamino]methyl}azetidin-3-ol; 3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-h- ydroxyazetidin- 3-yl]methyl}amino)propane-1,2-diol; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hy- droxyazetidin-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-hy- droxyazetidin-3- yl]methyl}-D-alanine; methyl N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbony- l)-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; N.sup.2-{[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-{[(pyr- rolidin-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-h- ydroxyazetidin- 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-{[(tra- ns-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-met- hylpyrrolidin-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-h- ydroxyazetidin- 3-yl]methyl}amino)-5-(hydroxymethyl)cyclopentane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-piperi- din-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-met- hylpiperidin-2- yl)azetidin-3-ol; 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hy- droxyazetidin-3- yl]methyl}guanidine; 1-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hy- droxyazetidin-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}carbony- l)-3- hydroxyazetidin-3-yl]ethyl}-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanam- ide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(pip- eridin-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-hy- droxyazetidin-3- yl]methyl}methanesulfonamide; 3-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-h- ydroxyazetidin- 3-yl]methyl}amino)-1H-pyrazol-5-ol; (1R,2S)-4-({[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbo- nyl)-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-m- ethyl-1H- pyrazol-3-yl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-eth- ylpyrrolidin-2- yl)azetidin-3-ol; (2R)-N-{(1S)-1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}ca- rbonyl)-3- hydroxyazetidin-3-yl]ethyl}-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanam- ide; 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-h- ydroxy-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)-bet- a-D-arabino- hexopyranoside; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pyridi- n-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}carbon- yl)-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-nit- roethyl)azetidin- 3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(3-f- luoro-4- hydroxyphenyl)amino]methyl}azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{[(2-f- luoro-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-py- rrol-2- yl)azetidin-3-ol; N-{[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hy- droxyazetidin-3- yl]methyl}benzenecarboximidamide; 3-({[(E)-1-amino-2-nitroethenyl]amino}methyl)-1-({3,4-difluoro-2-[(2-fluor- o-4- iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-met- hyl-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-i- midazol-2- ylamino)methyl]azetidin-3-ol; methyl {1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbony- l)-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-[(pyri- midin-2- ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(pyri- din-2- ylamino)methyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-met- hyl-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-met- hyl-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-carb- oxylate; 1-({2-[(4-bromo-2-chlorophenyl)amino]-3,4-difluorophenyl}carbonyl)-3-piper- idin-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-im- idazol-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]ph- enyl}carbonyl)- azetidin-3-ol; 1-({2-[(4-bromo-2-fluorophenyl)amino]-3,4-difluorophenyl}carbonyl)-3-piper- idin-2- ylazetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(3-met- hyl-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,2- S)-2- hydroxycyclohexyl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S,2- R)-2- hydroxycyclohexyl]azetidin-3-ol; 1-({3-fluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-pipe- ridin-2- yl]azetidin-3-ol; 1-({4-fluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-pipe- ridin-2- yl]azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(6-met- hylpiperidin-2- yl)azetidin-3-ol; and

1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-pipera- zin-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-pyrro- lidin-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-p- yrrolidin-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-p- yrrolidin-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-iod- ophenylamino)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-(m- ethylamino)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-[pipe- ridin-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]ph- enyl}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]ph- enyl}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-(pyrr- olidin-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-h- ydroxyazetidin-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-methy- lazetidin-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-{[(me- thyloxy)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-me- thylpyrrolidin-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-piper- azin-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-pyrro- lidin-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-p- yrrolidin-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-p- yrrolidin-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-iod- ophenylamino)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-(m- ethylamino)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-[pipe- ridin-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 there

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