Tricyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof

A compound of formula I:

• including all stereoisomers thereof, or a pharmaceutically acceptable salt thereof, wherein the compound of formula I is limited to formula BB as follows:
• K is N;
• Y is hydrogen, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halo, or alkoxy;
• R1 is
• Rm at each occurrence is independently selected from hydrogen, halogen, nitro, cyano, hydroxyl, alkoxy, —CO2(alkyl), —C(O)N(alkyl)2, alkyl, heteroarylalkyl, arylalkyl, aryl, and heteroaryl;
• R2 is elected from hydrogen, alkyl, alkenyl, alkynyl, alkoxy, amino, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloalkenyl, monoalkylaminoalkyl, dialkylaminoalkyl, cycloheteroalkylalkyl, hydroxyaryl, aryloxyalkyl, alkoxyalkyl, hydroxyalkyl, or a heterocyclic ring;
• R is independently selected from hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cyano, aryl, arylalkyl, aryloxy, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cycloalkyl, cycloalkylalkyl, cyanoalkyl, aminoalkyl, hydroxyalkyl, aryloxyalkyl, hydroxyaryl or NR1R2, wherein R1 and R2 are the same or different and are independently selected from hydrogen, alkyl, alkenyl, alkynyl, alkoxy, amino, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloalkenyl, monoalkylaminoalkyl, dialkylaminoalkyl, cycloheteroalkylalkyl, hydroxyaryl, aryloxyalkyl, alkoxyalkyl, hydroxyalkyl, or a heterocyclic ring;
• Ra is hydrogen, halo, alkyl, alkenyl, alkynyl, alkoxy, aryl, aryloxy, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cyano, heteroarylaminocarbonyl, cycloheteroalkylcarbonyl, cyanoalkyl, alkylaminoalkyl, hydroxyalkyl, hydroxyaryl, alkoxyalkyl, aryloxyalkyl, nitro, amino, CHO, CO2 alkyl, CONReRf, CH2NRgRh, CO2H, CH2OH, CH2NRH, NRgRh, NHCH2Rg, NHCHRgRh, NHCORe, NHCONReRf or NHSO2ReRf;
• Rb is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, aryloxy, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cyano, halo, heteroarylaminocarbonyl, cycloheteroalkylcarbonyl, cyanoalkyl, alkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, nitro, amino, CHO, CO2 alkyl, hydroxyaryl, aryloxyalkyl, CONRiRj, CH2NRkRl, CO2H, CH2OH, CH2NHRk, NHCH2Rk, NRkRl, NHCHRkRl, NHCORi, NHCONRiRj or NHSO2Ri;
• Rq and Rw are the same or different and are independently selected from hydrogen, halo, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, aryl, arylalkyl, aryloxy, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cyano, heteroarylaminocarbonyl, cycloheteroalkylcarbonyl, cyanoalkyl, alkylaminoalkyl, hydroxyalkyl, hydroxyaryl, aryloxyalkyl, nitro, amino, CHO, CO2 alkyl, CONReRf, CH2NRgRh, CO2H, CH2OH, CH2NHRg, NRgRh, NHCHR2Rg, NHCHRgRh, NHCORe, NHCONReRf, NHSO2ReRf, ═O, ═S, SRi, NHNRkRl, NHNRkCO2Ri, NHSO2Ri or a heterocyclic ring;
• where Re and Rf are the same or different and are independently selected from hydrogen, aryl, alkyl, alkenyl, alkynyl, alkoxy, amino, alkoxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cycloalkyl, or cycloalkylalkyl, and Re and Rf can be taken together with the nitrogen to which they are attached to form a 5-, 6- or 7-membered heteroaryl or cycloheteroalkyl ring which contains 1, 2 or 3 hetero atoms which can be N, O or S;
• Rg and Rh are the same or different and are independently selected from hydrogen, aryl, alkyl, alkenyl, alkynyl, alkoxy, amino, alkoxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cycloalkyl, or cycloalkylalkyl, and Rg and Rh can be taken together with the nitrogen to which they are attached to form a 5-, 6- or 7-membered heteroaryl ring or cycloheteroalkyl ring which contains 1, 2 or 3 hetero atoms which can be N, O or S;
• Ri and Rj are the same or different and are independently selected from hydrogen, aryl, alkyl, alkenyl, alkynyl, alkoxy, amino, alkoxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cycloalkyl, or cycloalkylalkyl, and Ri and Rj can be taken together with the nitrogen to which they are attached to form a 5-, 6- or 7-membered heteroaryl ring or cycloheteroalkyl ring which contains 1, 2 or 3 hetero atoms which can be N, O or S;
• and
• Rk and Rl are the same or different and are independently selected from hydrogen, aryl, alkyl, alkenyl, alkynyl, alkoxy, amino, alkoxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, cycloalkyl, or cycloalkylalkyl, and Rk and Rl can be taken together with the nitrogen to which they are attached to form a 5-, 6- or 7-membered heteroaryl ring or cycloheteroalkyl ring which contains 1, 2 or 3 hetero atoms which can be N, O or S;
• and
• Rc and Rd are the same or different and are independently selected from hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, hydroxy, aryloxy, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloheteroalkylalkyl, hydroxyaryl, or aryloxyalkyl;
• or
• Rc and Rd may optionally be taken together with the carbon to which they are attached to form a 3- to 7-membered ring which may optionally include an O atom or an N atom.