Spiro-hydantoin compounds useful as anti-inflammatory agents

A compound having the formula,

• 417
• or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, in which:
• L and K, taken independently, are O or S;
• R1a and R1b are independently selected from alkyl, substituted alkyl, halogen, cyano, nitro, OR10, NR10R11, C(═O)R10, CO2R10, C(═O)NR10R11, NR10C(═O)R11, NR10C(═O)OR11, SR10, S(O)oR10a, NR10SO2R10a, NHCH(alkyl)CO2R10, SO2NR10R11 cycloalkyl, heterocyclo, aryl, and heteroaryl;
• or alternatively, two R1b groups join together with each other or one R1b joins together with R1a to form a fused benzo ring;
• R2 is selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, heterocyclo, and heteraryl;
• R4a, and R4c are selected from halogen, alkyl, cyano, haloalkyl, haloalkoxy, aryloxy, arylthio, and nitro;
• R9 is selected from hydrogen and A1-Q-A2-R16;
• A1 is a bond, C1-2alkylene, or C2-3alkenylene;
• Q is a bond, —C(═O)—, —C(═O)NR17—, —SO2—, —CO2—, or —NR17CO2—;
• A2 is a bond, C1-3alkylene, C2-3alkenylene, —C1-4alkylene-NR17—, —C1-4alkylene-NR17C(═O)—, —C1-4alkylene-S—, —C1-4alkylene-SO2—, or —C1-4alkylene-O—, wherein said A2 alkylene groups are branched or straight chain and optionally substituted with a group selected from —CO2H, —CO2(C1-4alkyl), —S(C1-4alkyl), NH2, —NH(C1-4alkyl), or —N(C1-4alkyl)2;
• R10 and R11 (i) are selected independently of each other from hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclo;
• or (ii) R10 is taken together with R12 to form a heteroaryl or heterocyclo;
• R10a is alkyl, substituted alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclo;
• R16 is selected from alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, or heterocyclo, wherein each R16 is optionally substituted with one to three R18;
• R17 is hydrogen or alkyl;
• R18 is selected from C1-6alkyl, substituted C1-6alkyl, halogen, cyano, nitro, OR20, NR20R21, C(═O)R20, CO2R20, C(═O)NR20R21, C(═O)NR20SO2R20a, NR20C(═O)R21, NR20C(═O)OR21, SR20, S(O)uR20a, NR20SO2R20a, NHCH(alkyl)CO2R20, NH—(CH2)1-4—CO2R20, SO2NR20R21, C3-7cycloalkyl, phenyl, four to seven membered heterocyclo, or five or six membered heteroaryl, said C3-7cycloalkyl, phenyl, four to seven membered heterocyclo, or five or six membered heteroaryl groups in turn being optionally substituted with one to two R22;
• R20 and R21 are selected from hydrogen, alkyl, alkenyl, C3-7cycloalkyl, phenyl, benzyl, phenylethyl, napthyl, a four to seven membered heterocylo, or a five to six membered heteroaryl, or when attached to the same nitrogen atom may join to form a heterocyclo or heteroaryl;
• wherein each of R20 and R21 in turn is optionally substituted with one to two R22;
• R20a is selected from alkyl, alkenyl, CO2H, CO2(alkyl), C3-7cycloalkyl, phenyl, benzyl, phenylethyl, napthyl, a four to seven membered heterocylo, or a five to six membered heteroaryl;
• wherein each R20a in turn is optionally substituted with one to two R22;
• R22 is selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, hydroxy, cyano, CF3, O(C1-6alkyl), OCF3, C(═O)H, C(═O)(C1-6alkyl), CO2H, CO2(C1-6alkyl), NHCO2(C1-6alkyl), —S(C1-6alkyl), —NH2, NH(C1-6alkyl), N(C1-6alkyl)2, N(CH3)3+, SO2(C1-6alkyl), C(═O)(C1-4alkylene)NH2, C(═O)(C1-4alkylene)NH(alkyl), and C(═O)(C1-4alkylene)N(C1-4alkyl)2;
• o and u are independently 1 or 2;
• and
• n is 0, 1 or2.