US2017166523A9PendingUtilityA9
MEK Inhibitors And Methods Of Their Use
Est. expiryOct 7, 2025(expired)· nominal 20-yr term from priority
Inventors:Naing AayNeel K. AnandCharles M. BlazeyOwen Joseph BowlesJoerg BusseniusSimona CostanzoJeffry Kimo CurtisSteven Charles DefinaLarisa DubenkoAnagha Abhijit JoshiAbigail R. KennedyAngie Inyoung KimElena S. KoltunJean-Claire Limun ManaloCsaba J. PetoKenneth D. RiceTsze H. Tsang
A61P 35/00A61P 35/02A61P 43/00A61P 17/06A61P 17/02C07D 409/06C07D 403/12C07D 401/14C07D 401/06C07D 403/06C07D 405/12C07D 413/14C07D 401/04C07D 417/12C07D 409/12C07D 471/04C07D 205/06C07D 413/12C07D 403/04C07D 401/12C07D 205/04A61K 31/397
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Claims
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.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A compound of formula I:
or a pharmaceutically acceptable salt or solvate, thereof, wherein A, X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in Group A, Group B, Group C, or Group D:
Group A:
A is arylene optionally substituted with one, two, three or four groups selected from R 10 , R 12 , R 14 , R 16 , and R 19 where R 10 , R 12 , R 14 and R 16 are independently hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkoxy, hydroxy, alkoxy, amino, alkylamino, dialkylamino, haloalkyl, —NHS(O) 2 R 8 , —CN, —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ and —NR 8 C(O)R 8′ and where R 19 is hydrogen, alkyl, or alkenyl;
X is alkyl, halo, haloalkyl, or haloalkoxy;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently hydrogen, halo, nitro, —NR 8 R 8′ , —OR 8 , —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8′ , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; or one of R 1 and R 2 together with the carbon to which they are attached, R 3 and R 4 together with the carbon to which they are attached, and R 5 and R 6 together with the carbon to which they are attached form C(O) or C(═NOH);
m is 0, 1, or 2;
R 7 is hydrogen, halo or alkyl;
R 8 , R 8′ and R 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) n R 31 (where n is 0, 1, or 2 and R 31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —NR 34 SO 2 R 34a (where R 34 is hydrogen or alkyl and R 34a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl), —SO 2 NR 35 R 35a (where R 35 is hydrogen or alkyl and R 35a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl), —NR 32 C(O)R 32a (where R 32 is hydrogen or alkyl and R 32a is alkyl, alkenyl, alkoxy, or cycloalkyl), —NR 30 R 30′ (where R 30 and R 30′ are independently hydrogen, alkyl, or hydroxyalkyl), and —C(O)NR 33 R 33a (where R 33 is hydrogen or alkyl and R 33a is alkyl, alkenyl, alkynyl, or cycloalkyl); and
R 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;
Group B:
A is heteroarylene optionally substituted with one, two, three, or four groups selected from R 10 , R 12 , R 14 , R 16 and R 19 where R 10 , R 12 , R 14 and R 16 are independently hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkoxy, hydroxy, alkoxy, cyano, amino, alkylamino, dialkylamino, haloalkyl, alkylsulfonylamino, alkylcarbonyl, alkenylcarbonyl, alkoxycarbonyl, alkenyloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, or alkylcarbonylamino; where R 19 is hydrogen, alkyl, or alkenyl; and where each alkyl and alkenyl, either alone or as part of another group within R 10 , R 12 , R 14 , R 16 , and R 19 , is independently optionally substituted with halo, hydroxy, or alkoxy;
X is alkyl, halo, haloalkyl, or haloalkoxy;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently hydrogen, halo, nitro, —NR 8 R 8′ , —OR 8 , —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8′ , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; or one of R 1 and R 2 together with the carbon to which they are attached, R 3 and R 4 together with the carbon to which they are attached, and R 5 and R 6 together with the carbon to which they are attached form C(O) or C(═NOH);
m is 1 or 2;
R 7 is hydrogen, halo or alkyl; and
R 8 , R 8′ and R 8″ are independently selected from hydrogen, hydroxy, optionally substituted alkoxy, alkyl, haloalkyl, 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, carboxy ester, nitro, cyano, —S(O) n R 31 (where n is 0, 1, or 2 and R 31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —NR 36 S(O) 2 R 36a (where R 36 is hydrogen, alkyl, or alkenyl and R 36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —S(O) 2 NR 37 R 37a (where R 37 is hydrogen, alkyl, or alkenyl and R 37a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aryloxy, optionally substituted arylalkyloxy, optionally substituted heteroaryl, —NHC(O)R 32 (where R 32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and —NR 30 R 30′ (where R 30 and R 30′ are independently hydrogen, alkyl, or hydroxyalkyl), and —C(O)NHR 33 (where R 33 is alkyl, alkenyl, alkynyl, or cycloalkyl);
Group C:
A is
where R 10 is hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkoxy, hydroxy, alkoxy, amino, alkylamino, dialkylamino, haloalkyl, —NHS(O) 2 R 8 , —CN, —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ and NR 8 C(O)R 8′ ;
R 10a is hydrogen, alkyl, or alkenyl;
Y 1 is ═CH— or ═N—;
X is alkyl, halo, haloalkyl, or haloalkoxy;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently hydrogen, halo, nitro, —NR 8 R 8′ , —OR 8 , —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8′ , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; or one of R 1 and R 2 together with the carbon to which they are attached, R 3 and R 4 together with the carbon to which they are attached, and R 5 and R 6 together with the carbon to which they are attached form C(O) or C(═NOH);
m is 1 or 2;
R 7 is hydrogen, halo or alkyl; and
R 8 , R 8′ and R 8″ are independently selected from hydrogen, hydroxy, optionally substituted alkoxy, alkyl, haloalkyl, 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, carboxy ester, nitro, cyano, —S(O) n R 31 (where n is 0, 1, or 2 and R 31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —NR 36 S(O) 2 R 36a (where R 36 is hydrogen, alkyl, or alkenyl and R 36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —S(O) 2 NR 37 R 37a (where R 37 is hydrogen, alkyl, or alkenyl and R 37a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aryloxy, optionally substituted arylalkyloxy, optionally substituted heteroaryl, —NHC(O)R 32 (where R 32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and —NR 30 R 30′ (where R 30 and R 30′ are independently hydrogen, alkyl, or hydroxyalkyl), and —C(O)NHR 33 (where R 33 is alkyl, alkenyl, alkynyl, or cycloalkyl); or
Group D:
A is
R 40 and R 40a are independently hydrogen or alkyl;
X is alkyl, halo, haloalkyl, or haloalkoxy;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently hydrogen, halo, nitro, —NR 8 R 8 , —OR 8 , —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8 , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; or one of R 1 and R 2 together with the carbon to which they are attached, R 3 and R 4 together with the carbon to which they are attached, and R 5 and R 6 together with the carbon to which they are attached form C(O) or C(═NOH);
m is 1 or 2;
R 7 is hydrogen, halo or alkyl; and
R 8 , R 8′ and R 8′ are independently selected from hydrogen, hydroxy, optionally substituted alkoxy, alkyl, haloalkyl, 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, carboxy ester, nitro, cyano, —S(O). R 31 (where n is 0, 1, or 2 and R 31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —NR 36 S(O) 2 R 36a (where R 36 is hydrogen, alkyl, or alkenyl and R 36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), —S(O) 2 NR 37 R 37a (where R 37 is hydrogen, alkyl, or alkenyl and R 37a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aryloxy, optionally substituted arylalkyloxy, optionally substituted heteroaryl, —NHC(O)R 32 (where R 32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and —NR 30 R 30′ (where R 30 and R 30′ are independently hydrogen, alkyl, or hydroxyalkyl), and —C(O)NHR 33 (where R 33 is alkyl, alkenyl, alkynyl, or cycloalkyl).
2 . The Compound of claim 1 selected from Group A, Group B, and Group C where
Group A
A is phenylene optionally substituted with one or two groups selected from R 10 , R 12 , R 14 , and R 16 where R 10 , R 12 , R 14 and R 16 are independently hydrogen or halo;
X is halo;
R 1 , R 2 , R 5 and R 6 are hydrogen;
R 3 is hydrogen, halo, hydroxy, alkoxy, or amino;
R 4 is hydrogen, —NR 8 R 8′ , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 2 ), alkyl, alkenyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three groups independently selected from —OR 8 , halo, nitro, —S(O) m R 9 , optionally substituted heterocycloalkyl, —NR 8 R 8 , —NR 8 C(O)R 8 , —NR 8 S(O) 2 R 9 , —NR 8 C(O)OR 8 , and aryl; where the cycloalkyl is optionally substituted with one or two groups selected from —OR 8 and —NR 8 R 8′ ; where the heterocycloalkyl is optionally substituted with one or two groups independently selected from alkyl and —C(O)OR 8 ; and where the heteroaryl is optionally substituted with —NR 8 R 8′ ; or
R 3 and R 4 together with the carbon to which they are attached form C(O) or C(═NOH);
m is 0;
R 7 is halo;
R 8 and R 8′ are independently selected from hydrogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heterocycloalkyl, heteroaryl, and cycloalkyl;
where the R 8 and R 8′ alkyl are independently optionally substituted with one, two, or three groups independently selected from hydroxy, —NR 30 R 30′ (where R 30 and R 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 33 R 33a (where R 33 is hydrogen or alkyl and R 33a is alkyl, alkenyl, alkynyl, or cycloalkyl), optionally substituted aryloxy, —S(O) n R 31 (where n is 0 and R 31 is alkyl), carboxy, alkoxycarbonyl, and —NR 32 C(O)R 32a (where R 32 is hydrogen or alkyl and R 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 8 and R 8′ heteroaryl are independently optionally substituted with one or two groups independently selected from amino and alkyl;
where the R 8 and R 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 8 and R 8′ aryl are independently optionally substituted with one or two groups independently selected from hydroxy, alkoxy, halo, —NR 32 C(O)R 32a (where R 32 is hydrogen or alkyl and R 32a is alkyl, alkenyl, alkoxy, or cycloalkyl), and —NR 34 SO 2 R 34a (where R 34 is hydrogen or alkyl and R 34a is alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl); and
where the R 8 and R 8′ cycloalkyl are independently optionally substituted with one, two, or three groups independently selected from hydroxy, hydroxyalkyl, alkoxy, carboxy, —C(O)NR 33 R 33a (where R 33 is hydrogen or alkyl and R 33a is alkyl, alkenyl, alkynyl, or cycloalkyl), and optionally substituted cycloalkyl; and
R 9 is alkyl or aryl;
Group B
A is thien-3,4-diyl, benzo[d]isoxazol-5,6-diyl, 1H-indazol-5,6-diyl (optionally substituted at the N1 position with R 19 where R 19 is alkyl or alkenyl), benzo[d]oxazol-5,6-diyl, 1H-benzo[d]imidazol-5,6-diyl (optionally substituted at the N1 position with R 19 where R 19 is alkyl or alkenyl), 1H-benzo[d][1,2,3]triazol-5,6-diyl (optionally substituted at the N1 position with R 19 where R 19 is alkyl or alkenyl), imidazo[1,2-a]pyridin-6,7-diyl, cinnolin-6,7-diyl, quinolin-6,7-diyl, pyridin-3,4-diyl, 1-oxido-pyridin-3,4-diyl, [1,2,4]triazolo[4,3-a]pyridin-6,7-diyl, or 2,3-dihydroimidazo[1,2-a]pyridin-6,7-diyl; where A is optionally substituted with one, two, or three groups independently selected from R 10 , R 12 , R 14 , R 16 and R 19 where R 10 , R 12 , R 14 and R 16 are independently hydrogen, alkyl, halo, or amino;
and R 19 is hydrogen or alkyl;
X is halo;
R 1 , R 2 , R 5 and R 6 are hydrogen;
R 3 is hydrogen or hydroxy;
R 4 is —NR 8 R 8′ , heterocycloalkyl, heteroaryl, or alkyl; where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl;
R 7 is halo;
R 8 is hydrogen or alkyl; and
R 8′ is hydrogen, alkyl, or cycloalkyl; where the cycloalkyl is optionally substituted with one or two groups independently selected from hydroxy and alkyl;
Group C
A is
R 10 is hydrogen or halo;
R 10a is hydrogen or alkyl;
Y 1 is ═CH— or ═N—;
X is halo;
R 1 , R 2 , R 5 and R 6 are hydrogen;
R 3 is hydrogen or hydroxy;
R 4 is —NR 8 R 8′ , heterocycloalkyl, heteroaryl, or alkyl; where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl;
R 7 is halo;
R 8 is hydrogen or alkyl; and
R 8′ is hydrogen, alkyl, or cycloalkyl; where the cycloalkyl is optionally substituted with one or two groups independently selected from hydroxy and alkyl.
3 . The compound of claim 1 where R 3 is halo, nitro, —NR 8 R 8′ , —OR 8 , —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8′ , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8 , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; and R 4 is as defined in claim 1 ; or R 3 and R 4 together with the carbon to which they are attached form C(O) or C(═NOH).
4 . The compound of claim 1 where R 3 and R 4 are independently halo, nitro, —NR 8 R 8′ , —OR 8 , —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8′ , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25 b)═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; or R 3 and R 4 together with the carbon to which they are attached form C(O) or C(═NOH).
5 . The compound according to claim 1 wherein R 7 is halo.
6 . The compound according to claim 1 wherein X is halo.
7 . The compound according to claim 1 wherein R 1 , R 2 , R 5 , and R 6 are hydrogen.
8 . The compound of claim 1 selected from Group A where A is phenylene; and R 4 is —NR 8 R 8′ (where R 8 is hydrogen, hydroxy, alkyl, alkoxy, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl and R 8′ is hydroxy, alkoxy, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl), —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; or R 3 and R 4 together with the carbon to which they are attached form C(O) or C(═NOH).
9 . The compound of claim 1 where R 3 is hydrogen, halo, hydroxy, amino, or alkoxy.
10 . The compound of claim 1 where R 4 is hydrogen, —NR 8 R 8′ , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH) (N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 2 ), alkyl, alkenyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three —OR 8 , halo, nitro, —S(O) m R 9 , optionally substituted heterocycloalkyl, —NR 8 R 8′ , —NR 8 C(O)R 8′ , —NR 8 S(O) 2 R 9 , —NR 8 C(O)OR 8′ , aryl; where the cycloalkyl is optionally substituted with one or two —NR 8 R 8′ ; where the heterocycloalkyl is optionally substituted with one or two groups independently selected from alkyl and —C(O)OR 8 ; and where the heteroaryl is optionally substituted with —NR 8 R 8′ .
11 . The compound of claim 1 selected from Group A where A is phenylene optionally substituted with one or two groups independently selected from R 10 , R 12 , R 14 , and R 16 where R 10 , R 12 , R 14 and R 16 are independently hydrogen or halo.
12 . The compound of claim 1 selected from Group A where A is phenylene; R 3 is hydrogen; and R 4 is hydrogen, —NR 8 R 8′ , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , alkyl, or heterocycloalkyl; where the alkyl is optionally substituted with one or two groups independently selected from —OR 8 and —NR 8 R 8′ ; and where the heterocycloalkyl is optionally substituted with —NR 8 R 8′ .
13 . The compound of claim 1 selected from Group A where A is phenylene; R 3 is alkoxy; and R 4 is alkyl or heterocycloalkyl where the alkyl is substituted with —NR 8 R 8′ .
14 . The compound of claim 1 selected from Group A where A is phenylene; R 3 is halo; and R 4 is alkyl or heterocycloalkyl where the alkyl is substituted with —NR 8 R 8′ .
15 . The compound of claim 1 selected from Group A where A is phenylene and R 3 and R 4 together with the carbon to which they are attached form C(O) or C(═NOH).
16 . The compound of claim 1 selected from Group A where A is phenylene; R 3 is hydroxy; and R 4 is hydrogen, —C(O)NR 8 R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH) (N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH) (N(R 25a )(CN)), —CH 2 NR 25 C(═NH) (R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 2 ), alkyl, alkenyl, heterocycloalkyl, cycloalkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with one, two, or three groups selected from —OR 8 , halo, nitro, —S(O) m R 9 , optionally substituted heterocycloalkyl, —NR 8 R 8′ , —NR 8 C(O)R 8′ , optionally substituted heteroaryl, —NR 8 S(O) 2 R 9 , —NR 8 C(O)OR 8′ , and aryl; where the cycloalkyl is optionally substituted with one or two groups independently selected from —NR 8 R 8′ and —C(O)NR 33 R 33a ; where the heterocycloalkyl is optionally substituted with one, two or three groups independently selected from alkyl and —C(O)OR 8 ; and where the heteroaryl is optionally substituted with —NR 8 R 8′ .
17 . The compound of claim 1 selected from Group A where A is phenylene; R 7 is iodo or bromo; X is fluoro or chloro; and R 1 , R 2 , R 5 , and R 6 are hydrogen; and R 10 , R 12 , R 14 , and R 16 are independently hydrogen or fluoro.
18 . The compound of claim 17 where R 10 is 3-fluoro and R 12 , R 14 , and R 16 are hydrogen or halo; R 10 is 3-fluoro, R 12 is 4-fluoro, and R 14 and R 16 are hydrogen; R 10 is 4-fluoro, R 12 is 5-fluoro, and R 14 and R 16 are hydrogen; R 10 is 4-fluoro, R 12 is 6-fluoro, and R 14 and R 16 are hydrogen; or R 12 is 4-fluoro and R 10 , R 14 , and R 16 are hydrogen.
19 . The Compound of claim 1 selected from Group A where A is phenylene and R 3 is hydroxy.
20 . The Compound of claim 19 where R 4 is —C(O)NR 8 R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ; or where the alkyl is optionally substituted with one, two, three, four, five, six or seven halo.
21 . The Compound of claim 20 where R 4 is alkyl, heterocycloalkyl, or heteroaryl; where the alkyl is optionally substituted with —NR 8 R 8′ ; where the heterocycloalkyl is optionally substituted with alkyl or —C(O)OR 8 ; and where the heteroaryl is optionally substituted with alkyl.
22 . The Compound of claim 1 where
R 1 is halo, nitro, —NR 8 R 8′ , —OR 8 , —NHS(O) 2 R 8 , —CN, —S(O) m R 8 , —S(O) 2 NR 8 R 8′ , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)OR 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ , —NR 8 C(O)R 8′ , —CH 2 N(R 25 )(NR 25a R 25b ), CH 2 NR 25 C(═NH)(NR 25a R 25b ), —CH 2 NR 25 C(═NH)(N(R 25a )(NO 2 )), —CH 2 NR 25 C(═NH)(N(R 25a )(CN)), —CH 2 NR 25 C(═NH)(R 25 ), or —CH 2 NR 25 C(NR 25a R 25b )═CH(NO 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 8 , —NR 8 R 8′ , —NR 8 S(O) 2 R 9 , —CN, —S(O) m R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)NR 8′ R 8″ , —NR 8 C(O)OR 8′ and —NR 8 C(O)R 8′ ;
R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
23 . The Compound of claim 1 selected from Group B where A is thien-3,4-diyl, benzo[d]isoxazol-5,6-diyl, 1H-indazol-5,6-diyl (optionally substituted at the N1 position with R 19 where R 19 is alkyl or alkenyl), benzo[d]oxazol-5,6-diyl, 1H-benzo[d]imidazol-5,6-diyl (optionally substituted at the N1 position with R 19 where R 19 is alkyl or alkenyl), 1H-benzo[d][1,2,3]triazol-5,6-diyl (optionally substituted at the N1 position with R 19 where R 19 is alkyl or alkenyl), imidazo[1,2-a]pyridin-6,7-diyl, cinnolin-6,7-diyl, quinolin-6,7-diyl, pyridin-3,4-diyl, 1-oxido-pyridin-3,4-diyl, [1,2,4]triazolo[4,3-a]pyridin-6,7-diyl, or 2,3-dihydroimidazo[1,2-a]pyridin-6,7-diyl.
24 . The Compound of claim 1 where A is thien-3,4-diyl; R 10 and R 12 are hydrogen; X and R 7 are halo; and R 1 , R 2 , R 5 , and R 6 are hydrogen.
25 . The Compound of claim 24 where R 3 is hydrogen or hydroxy; and R 4 is —NR 8 R 8′ , heterocycloalkyl, heteroaryl, or alkyl, where the alkyl is optionally substituted with —NR 8 R 8′ .
26 . The Compound of claim 1 selected from Group B where A is benzo[d]isoxazol-5,6-diyl; R 10 , R 12 , and R 14 are independently hydrogen, halo, or alkyl; R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
27 . The Compound of claim 23 according to Formula I(g) or I(h):
where R 10 , R 12 , and R 14 are independently hydrogen, halo, or alkyl; R 19 is alkyl or alkenyl; R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
28 . The Compound of claim 23 according to Formula I(i) or I(j):
where R 10 , R 12 , and R 14 are independently hydrogen, halo, or alkyl; R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
29 . The Compound of 23 according to Formula I(n) or I(o):
where R 7 is halo or alkyl; X is halo; R 19 is alkyl; R 1 , R 2 , R 5 , and R 6 are hydrogen; R 10 , R 12 , and R 14 are independently hydrogen or halo; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
30 . The Compound of 23 according to Formula I(p):
where R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 10 and R 12 are independently hydrogen, halo, or alkyl; R 19 is hydrogen or alkyl; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
31 . The Compound of 23 according to Formula I(q):
where R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 10 , R 12 , R 14 , and R 16 are independently hydrogen or halo; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
32 . The Compound of 23 according to Formula I(r):
where R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 10 and R 12 are independently hydrogen, halo, or alkyl; R 14 is hydrogen, halo, alkyl, or amino; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
33 . The Compound of 23 according to Formula I(s):
R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 10 and R 12 are independently hydrogen, halo, or alkyl; R 14 is hydrogen, halo, alkyl, or amino; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
34 . The Compound of 23 according to Formula I(u), I(v), I(w), or I(x):
where R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 10 , R 12 , and R 14 are independently hydrogen, halo, or alkyl; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
35 . The Compound of claim 1 selected from Group C and according to Formula I(y) or I(z):
where R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 10 is hydrogen, halo, or alkyl; R 10a is alkyl; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
36 . The Compound of claim 1 selected from Group D and according to Formula I(aa) or I(bb):
where R 1 , R 2 , R 5 , and R 6 are hydrogen; X and R 7 are halo; R 3 is hydroxy; and R 4 is heterocycloalkyl, alkyl, or heteroaryl, where the alkyl is optionally substituted with —NR 8 R 8′ and where the heteroaryl is optionally substituted with alkyl.
37 . 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-methyipropanamide;
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-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}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-methylpyffolidin-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)-azetidin-3-yl]N,N-diethylglycinamide; dimethylpyrrolidindin-3-amine;
1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]-N,N-dimethylpynolidin-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;
3-[(dimethylamino)methyl]-1-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)azetidin 3-ol;
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]pheny }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-(1-1,2,3-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-methylpyffolidin-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-methylbutyl) 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-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-{[(1,1,3,3-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-inden-1-ylamino) methyl]azetidin-3-ol;
1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[({2-[(phenylmethyl) oxy]cyclopentyl}amino)methyl]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-difluoro-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-({[3-(methylthio) propyl]amino}methyl)azetidin-3-ol;
N-cyclohexyl-N˜2˜-{[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 [3.3.1.1˜3,7˜]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-[(1S)-1-aminoethyl]-1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-α]pyridin-6-yl}carbonyl) azetidin-3-ol;
1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-α]pyridin-6-yl}carbonyl)-3-[(1S)-1-(methylamino) ethyl]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˜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;
3-(1H-benzimidazol-2-yl)-1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo [1,2-α]pyridin-6-yl}carbonyl) azetidin-3-ol;
3-(1H-benzimidazol-2-yl)-1-({7-[(4-bromo-2-fluorophenyl)amino]-8-fluoroimidazo[1,2-α]pyridin-6-yl}carbonyl) 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-dimethylethyl4-[({[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}1-3,3,3-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;
3-{[(1,1-dimethylethyl)amino]methyl}-1-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)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}methane sulfonamide;
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-ethylpyffolidin-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]ethyl1-3,3,3-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;
3-(1-aminoethyl)-1-({8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}carbonyl) azetidin-3-ol;
1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-α]pyridin-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-α]pyridin-6-yl}carbonyl)-3-{(1S)-1-[(2-hydroxy-2-methylcyclopentyl) amino]ethyl}azetidin-3-ol
1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1H-imidazol-2-yl) 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;
1-({2-fluoro-3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2S)-pyffolidin-2-yl]azetidin-3-ol;
1-({8-fluoro-7-[(2-fluoro-4-iodophenyl)amino]-4-methylcinnolin-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]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-({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1-methyl-1H-benzimidazol-6-yl}carbonyl) -3-piperidin-2-ylazetidin-3-ol;
1-({5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazol-6-yl}carbonyl)-3-[(2S) -piperidin-2-yl]azetidin-3-ol;
1-({8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}carbonyl)-3-piperidin-2-ylazetidin-3-ol;
1-({2-[(4-bromo-2-fluorophenyl)amino]-3,4-difluorophenyl}carbonyl)-3-piperidin-2-ylazetidin-3-ol;
1-({7-[(4-bromo-2-fluorophenyl)amino]-8-fluoroimidazo[1,2-α]pyridin-6-yl}carbonyl)-3-[(2S) -piperidin-2-yl]azetidin-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-({7-[(4-bromo-2-chlorophenyl)amino]-8-chloroimidazo[1,2-a]pyridin-6-yl}carbonyl)-3-piperidin-2-ylazetidin-3-ol;
1-({8-chloro-7-[(2-fluoro-4-iodophenyl)amino]imidazo[1,2-a]pyridin-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({7-[(4-bromo-2-chlorophenyl)amino]- 8-chloroimidazo[1,2-a]pyridin-6-yl }carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1--({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1-methyl-1H-benzimidazol-6-yl}carbonyl)-3-[(2S) -piperidin-2-yl]azetidin-3-ol;
3-[(1S)-1-aminoethyl]-1-({5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazol-6-yl}carbonyl) azetidin-3-ol;
1-({5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-1-methyl-1H-benzimidazol-6-yl}carbonyl)-3-[(1S) -1-(methylamino)ethyl]azetidin-3-ol;
4-[(4-bromo-2-fluorophenyl)amino]-3-fluoro-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl}carbonyl) pyridin-2(1H)-one;
4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl}carbonyl)-1-methylpyridin-2 (1H)-one;
4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl}carbonyl)-1-methylpyridin-2 (1H)-one;
1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S,2S)-2-hydroxycyclohexyl]azetidin-3-ol;
4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(1S)-1-(methylamino)propyl]azetidin-1-yl}carbonyl)-1-methylpyridin-2 (1H)-one;
1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(1S,2R)-2-hydroxycyclohexyl]azetidin-3-ol;
5-({3-[(1S)-1-(dimethylamino)ethyl]-3-hydroxyazetidin-1-yl}carbonyl)-4-[(2-fluoro-4-iodophenyl) amino]-1-methylpyridin-2(1H)-one;
4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(methylamino)methyl]azetidin-1-yl}carbonyl)-1-methylpyridin-2 (1H)-one;
5-{[3-(1H-benzimidazol-2-yl)-3-hydroxyazetidin-1-yl]carbonyl1-4-[(4-bromo-2-fluorophenyl) amino]-1-methylpyridin-2(1H)-one;
4-[(4-bromo-2-fluorophenyl)amino]-5-{[3-hydroxy-3-(1-methyl-1H-benzimidazol-2-yl) azetidin-1-yl]carbonyl}-1-methylpyridin-2(1H)-one;
4-[(4-bromo-2-fluorophenyl)amino]-5-({3-hydroxy-3-[(2S)-pyrrolidin-2-yl]azetidin-1-yl}carbonyl)-1-methylpyridin-2 (1H)-one;
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-({6-[(4-bromo-2-chlorophenyl)amino]-7-fluoro-3-methyl-1,2-benzisoxazol-5-yl}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;
1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-piperazin-2-ylazetidin-3-ol;
5-[(2-fluoro-4-iodophenyl)amino]-6-({3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl}carbonyl)-2-methylpyridazin-3 (2H)-one;
5-[(4-bromo-2-chlorophenyl)amino]-6-({3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl}carbonyl)-2-methylpyridazin-3 (2H)-one;
5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-6-({3-hydroxy-3-[(2S)-pyrrolidin-2-yl]azetidin-1-yl}carbonyl)-2-methylpyridazin-3 (2H)-one;
5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-6-({3-hydroxy-3-[(2R)-pyffolidin-2-yl]azetidin-1-yl }carbonyl)-2-methylpyridazin-3 (2H)-one;
6-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-5-[(2-fluoro-4-iodophenyl) amino]-2-methylpyridazin-3(2H)-one;
6-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-5-[(4-bromo-2-chlorophenyl) amino]-2-methylpyridazin-3(2H)-one;
5-[(4-bromo-2-chlorophenyl)amino]-6-{[3-((1S)-1-{[(3R,4S)-3,4-dihydroxycyclopentyl]amino}ethyl)-3-hydroxyazetidin-1-yl]carbonyl}-2-methylpyridazin-3 (2H)-one;
5-[(4-bromo-2-fluorophenyl)amino]-6-[(3-hydroxy-3-{(1S)-1-[(2-hydroxy-2-methylcyclopentyl) amino]propyl}azetidin-1-yl)carbonyl]-2-methylpyridazin-3(2H)-one
6-({3-[(1S)-1-aminopropyl]-3-hydroxyazetidin-1-yl}carbonyl)-5-[(4-bromo-2-fluorophenyl) amino]-2-methylpyridazin-3(2H)-one;
6-{[3-(1H-benzimidazol-2-yl)-3-hydroxyazetidin-1-yl]carbonyl1-5-[(2-fluoro-4-iodophenyl) amino]-2-methylpyridazin-3(2H)-one;
5-[(2-fluoro-4-iodophenyl)amino]-6-{[3-hydroxy-3-(1-methyl-1H-benzimidazol-2-yl)azetidin-1-yl]carbonyl}-2-methylpyridazin-3 (2H)-one;
1-({2-fluoro-3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({3-[(2-fluoro-4-iodophenyl)amino]-1-oxidopyridin-4-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({2-fluoro-3-[(2-fluoro-4-bromophenyl)amino]pyridin-4-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
3-[(1S)-1-aminopropyl]-1-({3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl) azetidin-3-ol;
1-({3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-[(1S)-1-(methylamino)propyl]azetidin-3-ol;
(1R,2S)-4-({(1S)-1-[1-({2-fluoro-3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-hydroxyazetidin-3-yl]propyl}amino) cyclopentane-1,2-diol;
1-({7-[(4-bromo-2-chlorophenyl)amino]- 8-fluoro-4-methylcinnolin-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({7-[(4-bromo-2-fluorophenyl)amino]-8-fluoro-4-methylcinnolin-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
3-[(1S)-1-aminoethyl]-1-({7-[(4-bromo-2-fluorophenyl)amino]cinnolin-6-yl}carbonyl)azetidin3-ol;
1-({7-[(4-bromo-2-fluorophenyl)amino]cinnolin-6-yl }carbonyl)-3-{(1S)-1-[(2-hydroxy-2-methylcyclopentyl) amino]ethyl}azetidin-3-ol;
1-({7-[(4-bromo-2-fluorophenyl)amino]cinnolin-6-yl}carbonyl)-3-[(1S)-1-(dimethylamino) ethyl]azetidin-3-ol;
3-[(1S)-1-aminoethyl]-1-({5-[(2-fluoro-4-iodophenyl)amino]- 1-1,2,3-benzotriazol-6-yl}carbonyl) azetidin-3-ol;
3-[(1S)-1-(dimethylamino)ethyl]-1-({5-[(2-fluoro-4-iodophenyl)amino]-1-methyl-1H-1,2,3-benzotriazol-6-yl}carbonyl) azetidin-3-ol;
1-({5-[(2-fluoro-4-iodophenyl)amino]- 1H1,2,3-benzotriazol-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({5-[(2-fluoro-4-iodophenyl)amino]-1-methyl-1H-1,2,3-benzotriazol-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
1-({5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2,3-benzotriazol-6-yl}carbonyl)-3-{(1S)-1-[(2-hydroxy-2-methylcyclopentyl) amino]ethyl}azetidin-3-ol;
3-[(1S)-1-aminoethyl]-1-({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2,3-benzotriazol-6-yl}carbonyl)azetidin-3-ol;
1-({4-fluoro-5-[(2-fluoro-4-iodophenyl)amino]-1H-1,2,3-benzotriazol-6-yl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol;
5-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-6-[(2-fluoro-4-iodophenyl) amino]pyrimidin-2(1H)-one;
6-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl}carbonyl) pyrimidin-2(1H)-one;
4-[(2-fluoro-4-iodophenyl)amino]-5-({3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl}carbonyl) pyrimidin-2(1H)-one; and
5-({3-[(1S)-1-aminoethyl]-3-hydroxyazetidin-1-yl}carbonyl)-4-[(2-fluoro-4-iodophenyl) amino]pyrimidin-2(1H)-one.
38 . A pharmaceutical composition comprising a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier, excipient, or diluent.
39 . A method of inhibiting MEK comprising administering to a patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, and optionally a pharmaceutically acceptable carrier, excipient, or diluent.
40 . A method of treating a disease, disorder, or syndrome which method comprises administering to a patient a compound of Formula I or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I and a pharmaceutically acceptable carrier, excipient, or diluent.
41 . The method of claim 40 where the disease is a proliferative disease.
42 . A method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I and a pharmaceutically acceptable carrier, excipient, or diluent.
43 . The method of claim 42 where the cancer is melanoma, colon cancer, rectal cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, small cell lung cancer, papillary and anaplastic thyroid cancer, endometrial cancer, or ovarian cancer.Cited by (0)
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