Details for Patent: 8,362,002

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. (San Francisco, CA)
Filing Date:	Mar 15, 2011
Application Number:	13/048,832
Claims:	1. A method of treating a disease, wherein treating means inhibiting the disease, and wherein the disease is a cancer selected from melanoma, colorectal cancer, pancreatic cancer, breast cancer, non-small cell lung cancer, small cell lung cancer, papillary and anaplastic thyroid cancer, endometrial cancer, and ovarian cancer, comprising administering to a patient a therapeutically effective amount of a compound of formula I, or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I, or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent, wherein the compound of formula I is: ##STR00470## or 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'', --N R.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, --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.3OR.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.25a is hydrogen, alkyl, or alkenyl; Group B: A is heteroarylene optionally substituted with one, two, three, or four groups selected from R.sup.10, R.sup.12, R.sup.14, R.sup.16 and R.sup.19 where R.sup.10, R.sup.12, R.sup.14 and R.sup.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.sup.19 is hydrogen, alkyl, or alkenyl; and where each alkyl and alkenyl, either alone or as part of another group within R.sup.10, R.sup.12, R.sup.14, R.sup.16, and R.sup.19, is independently optionally substituted with halo, hydroxy, or alkoxy; 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', --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'', --N R.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, --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 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.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).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.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.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.3OR.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl; Group C: A is ##STR00471## where R.sup.10 is 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'; R.sup.10a is hydrogen, alkyl, or alkenyl; Y.sup.1 is .dbd.CH-- or .dbd.N--; 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'', --N R.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, --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 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.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).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.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.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); or R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl; Group D: A is ##STR00472## R.sup.40 and R.sup.40a are independently hydrogen or alkyl; 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'', --N R.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, --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 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.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).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.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.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.3OR.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 2. A method of inhibiting MEK comprising administering to a patient a therapeutically effective amount of a compound of formula I, or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I, or a single stereoisomer or mixture of stereoisomers thereof and optionally as a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, or diluent, wherein the compound of formula I is: ##STR00473## 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'', --N R.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, --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.25a is hydrogen, alkyl, or alkenyl; Group B: A is heteroarylene optionally substituted with one, two, three, or four groups selected from R.sup.10, R.sup.12, R.sup.14, R.sup.16 and R.sup.19 where R.sup.10, R.sup.12, R.sup.14 and R.sup.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.sup.19 is hydrogen, alkyl, or alkenyl; and where each alkyl and alkenyl, either alone or as part of another group within R.sup.10, R.sup.12, R.sup.14, R.sup.16, and R.sup.19, is independently optionally substituted with halo, hydroxy, or alkoxy; 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'', --N R.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, --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 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.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).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.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.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl; Group C: A is ##STR00474## where R.sup.10 is 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'; R.sup.10a is hydrogen, alkyl, or alkenyl; Y.sup.1 is .dbd.CH-- or .dbd.N--; 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'', --N R.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, --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 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.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).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.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.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); or R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl; Group D: A is ##STR00475## R.sup.40 and R.sup.40a are independently hydrogen or alkyl; 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'', --N R.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, --OR.sup.8, --NR.sup.8R.sup.8', --NR.sup.8S(O).sub.2R.sup.9, --CN, --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 1 or 2; R.sup.7 is hydrogen, halo or alkyl; and R.sup.8, R.sup.8' and R.sup.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).sub.nR.sup.31 (where n is 0, 1, or 2 and R.sup.31 is optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --NR.sup.36S(O).sub.2R.sup.36a (where R.sup.36 is hydrogen, alkyl, or alkenyl and R.sup.36a is alkyl, alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl), --S(O).sub.2NR.sup.37R.sup.37a (where R.sup.37 is hydrogen, alkyl, or alkenyl and R.sup.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.sup.32 (where R.sup.32 is alkyl, alkenyl, alkoxy, or cycloalkyl) and --NR.sup.30R.sup.30' (where R.sup.30 and R.sup.30' are independently hydrogen, alkyl, or hydroxyalkyl), and --C(O)NHR.sup.33 (where R.sup.33 is alkyl, alkenyl, alkynyl, or cycloalkyl); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 3. The method of claim 1 wherein the compound of formula I is 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.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; 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.sup.19 where R.sup.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.sup.19 where R.sup.19 is alkyl or alkenyl), 1H-benzo [d][1,2,3]triazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.19 is alkyl or alkenyl), imidazo[1,2-c]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.sup.10, R.sup.12, R.sup.14, R.sup.16 and R.sup.19 where R.sup.10, R.sup.12, R.sup.14 and R.sup.16 are independently hydrogen, alkyl, halo, or amino; and R.sup.19 is hydrogen or alkyl; X is halo; R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are hydrogen; R.sup.3 is hydrogen or hydroxy; R.sup.4 is --NR.sup.8R.sup.8', heterocycloalkyl, heteroaryl, or alkyl; where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl; R.sup.7 is halo; R.sup.8 is hydrogen or alkyl; and R.sup.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 ##STR00476## R.sup.10 is hydrogen or halo; R.sup.10a is hydrogen or alkyl; Y.sup.1 is .dbd.CH-- or .dbd.N--; X is halo; R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are hydrogen; R.sup.3 is hydrogen or hydroxy; R.sup.4 is --NR.sup.8R.sup.8', heterocycloalkyl, heteroaryl, or alkyl; where the alkyl is optionally substituted with --NR.sup.8R.sup.8' and where the heteroaryl is optionally substituted with alkyl; R.sup.7 is halo; R.sup.8 is hydrogen or alkyl; and R.sup.8' is hydrogen, alkyl, or cycloalkyl; where the cycloalkyl is optionally substituted with one or two groups independently selected from hydroxy and alkyl. 4. The method of claim 1, wherein the compound of formula I is 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); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 5. The method of claim 1, wherein the compound of formula I is 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); R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 6. The method of claim 1 wherein the compound of formula I is where R.sup.7 is halo. 7. The method of claim 1 wherein the compound of formula I is where X is halo. 8. The method of claim 1 wherein the compound of formula I is where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen. 9. The method of claim 1 wherein the compound of formula I is selected from Group A 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). 10. The method of claim 1 wherein the compound of formula I is where R.sup.3 is hydrogen, halo, hydroxy, amino, or alkoxy. 11. The method of claim 1 wherein the compound of formula I is 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'; R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 12. The method of claim 1 wherein the compound of formula I is selected from Group A 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. 13. The method of claim 1 wherein the compound of formula I is selected from Group A 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'. 14. The method of claim 1 wherein the compound of formula I is selected from Group A 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'. 15. The method of claim 1 wherein the compound of formula I is selected from Group A 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'. 16. The method of claim 1 wherein the compound of formula I is selected from Group A where R.sup.3 and R.sup.4 together with the carbon to which they are attached form C(O) or C(.dbd.NOH). 17. The method of claim 1 wherein the compound of formula I is selected from Group A 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'. 18. The method of claim 1 wherein the compound of formula I is selected from Group A 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. 19. The method of claim 18 wherein the compound of formula I is selected from Group A 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-fluro and R.sup.10, R.sup.14, and R.sup.16 are hydrogen. 20. The method of claim 1 wherein the compound of formula I is selected from Group A where R.sup.3 is hydroxy. 21. The method of claim 20 wherein the compound of formula I is selected from Group A 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.C H(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. 22. The method of claim 21 wherein the compound of formula I is selected from Group A 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. 23. The method of claim 1 wherein the compound of formula I is 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; R.sup.25 and R.sup.25b are independently hydrogen, alkyl, alkenyl, optionally substituted cycloalkyl, or optionally substituted aryl; and R.sup.25a is hydrogen, alkyl, or alkenyl. 24. The method of claim 1 wherein the compound of formula I is 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 Ni position with R.sup.19 where R.sup.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.sup.19 where R.sup.19 is alkyl or alkenyl), 1H-benzo[d][1,2,3]triazol-5,6-diyl (optionally substituted at the N1 position with R.sup.19 where R.sup.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. 25. The method of claim 1 wherein the compound of formula I is where A is thien-3,4-diyl; R.sup.10 and R.sup.12 are hydrogen; X and R.sup.7 are halo; and R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen. 26. The method of claim 25 wherein the compound of formula I is where R.sup.3 is hydrogen or hydroxy; and R.sup.4 is --NR.sup.8R.sup.8', heterocycloalkyl, heteroaryl, or alkyl, where the alkyl is optionally substituted with --NR.sup.8R.sup.8'. 27. The method of claim 1 wherein the compound of formula I is selected from Group B where A is benzo[d]isoxazol-5,6-diyl; R.sup.10, R.sup.12, R.sup.14 are independently hydrogen, halo, or alkyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; 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. 28. The method of claim 24 wherein the compound of formula I is according to Formula I(g) or I(h): ##STR00477## where R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen, halo, or alkyl; R.sup.19 is alkyl or alkenyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; 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. 29. The method of claim 24 wherein the compound of formula I is according to Formula I(i) or I(j): ##STR00478## where R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen, halo, or alkyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; 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. 30. The method of 24 wherein the compound of formula I is according to Formula I(n) or I(o): ##STR00479## where R.sup.7 is halo or alkyl; X is halo; R.sup.19 is alkyl; R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen or halo; 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. 31. The method of 24 wherein the compound of formula I is according to Formula I(p): ##STR00480## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 and R.sup.12 are independently hydrogen, halo, or alkyl; R.sup.19 is hydrogen or alkyl; 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. 32. The method of 24 wherein the compound of formula I is according to Formula I(q): ##STR00481## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10, R.sup.12, R.sup.14, and R.sup.16 are independently hydrogen or halo; 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. 33. The method of 24 wherein the compound of formula I is according to Formula I(r): ##STR00482## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 and R.sup.12 are independently hydrogen, halo, or alkyl; R.sup.14 is hydrogen, halo, alkyl, or amino; 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. 34. The method of 24 wherein the compound of formula I is according to Formula I(s): ##STR00483## R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 and R.sup.12 are independently hydrogen, halo, or alkyl; R.sup.14 is hydrogen, halo, alkyl, or amino; 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. 35. The method of 24 wherein the compound of formula I is according to Formula I(u), I(v), I(w), or I(x): ##STR00484## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10, R.sup.12, and R.sup.14 are independently hydrogen, halo, or alkyl; 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. 36. The method of claim 1 wherein the compound of formula I is selected from Group C and according to Formula I(y) or I(z): ##STR00485## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; R.sup.10 is hydrogen, halo, or alkyl; R.sup.10a is alkyl; 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. 37. The method of claim 1 wherein the compound of formula I is selected from Group D and according to Formula I(aa) or I(bb): ##STR00486## where R.sup.1, R.sup.2, R.sup.5, and R.sup.6 are hydrogen; X and R.sup.7 are halo; 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. 38. The method of claim 1 wherein the compound of formula I is selected from the group consisting of: 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}-carbonyl)azetidi- n-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)a- zetidin-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-(hydr- oxymethyl)azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(trif- luoromethyl)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-hy- droxyazetidin-3-yl]propane-1,2-diol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-ethyl- azetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-methy- lazetidin-3-ol; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-ethen- ylazetidin-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)azetidi- n-3-yl]methanol; 1-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hy- droxyazetidin-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)azetidi- n-3-yl]carbamate; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(pyrr- olidin-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-[(dim- ethylamino)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)azeti- din-3-yl]-2-methylpropanamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azeti- din-3-yl]formamide; N-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azeti- din-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)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-p- yrrolidin-2-ylazetidin-3-ol; (S)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-p- yrrolidin-2-ylazetidin-3-ol; 3-(aminomethyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}c- arbonyl)azetidin-3-ol; 3-[(1S)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]ph- enyl}carbonyl)azetidin-3-ol; 3-[(1R)-1-aminoethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]ph- enyl}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-ethyl- azetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2-hy- droxyethyl)azetidine-3-carboxamide; 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-N-(2-pi- peridin-1-ylethyl)azetidine-3-carboxamide; 1-({3,4-d