2-substituted 5-oxazolyl indole compounds useful as IMPDH inhibitors and pharmaceutical compositions comprising same

A compound having the formula (I),

• or a pharmaceutically-acceptable salt, hydrate, or prodrug thereof, wherein:
• R1 is independently selected from halogen, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, and
• R2 is independently selected from hydrogen, halogen, cyano, —C(═O)R6, —CO2R6, —SR6, —S(═O)R7, —SO2R7, and —SO3R7,
• or alternatively, R1 and R2 taken together form a fused (C5-6)carbocyclic ring or a fused five-to-six membered heterocyclo ring, said ring being optionally substituted with one to two groups selected from R8;
• R3 is C1-6alkyl, halo(C1-4alkyl), O(C1-6alkyl), halo(C1-4alkoxy), or halogen;
• R4 and R5 are independently selected from C1-6alkyl, substituted C1-6alkyl, halogen, cyano, and —OR9;
• R6 and R7 are selected from hydrogen, C1-6alkyl, substituted C1-6alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl, except R7 is not hydrogen;
• R8 is selected from C1-6alkyl, substituted C1-6alkyl, halogen, keto (═O), cyano, —OR11, —SR11, —NR11R12, —(C═O)R11, —CO2R11, —C(═O)NR11R12, —NR11C(═O)R12, NR11CO2R12, —OC(═O)R11, —OC(═O)NR11R12, —NR11C(═O)NR12R13, NR11SO2R14, —SO2NR11R12, SO2R14, SO3R14, cycloalkyl, aryl, heteroc heteroaryl;
• R9 is selected from hydrogen, C1-6alkyl, substituted C1-6alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl;
• R11, R12, R13 and R14 are selected from hydrogen, C1-6alkyl, cycloalkyl, aryl, heterocyclo, heteroaryl, and C1-6alkyl substituted with one, two or three of halogen, hydroxy, O(alkyl), O(phenyl), O(benzyl), nitro, cyano, —(C═O)H, —CO2H, —(C═O)alkyl, —CO2alkyl, —NH2, —NH(alkyl), —NH(cycloalkyl), —NH(aryl), —NH(heterocyclo), —N(alkyl)2, —C(═O)phenyl, —(C═O)NH2, —(C═O)NH(alkyl), —(C═O)NH(cycloalkyl), —(C═O)N(alkyl)2, phenyl, benzyl, C3-7cycloalkyl, four to seven membered heterocyclo, and/or five or six membered heteroaryl, provided, however, that R14 is not hydrogen when attached to a sulfonyl group as in —SO2R14 and —SO3R14;
• and
• m and n are 0, 1 or 2.

A compound having the formula (Ia),

• or a pharmaceutically-acceptable salt, hydrate, or prodrug thereof, wherein
• R1 is independently selected from halogen, phenyl, thienyl, thiazolyl, benzothienyl, and benzyl, and is optionally substituted with one to two R15;
• R2 is independently selected from hydrogen, halogen, cyano, —C(═O)R6, and —CO2R6,
• or alternatively, R1 and R2 taken together form
• which is fused to ring A sharing a common double bond therewith along the bond region designated with the symbol ;
• R6 is selected from hydrogen and C1-C4alkyl;
• R8 and R15 are at each occurrence independently selected from alkyl, alkenyl, halogen, haloalkyl, haloalkoxy, cyano, nitro, phenyl, benzyl, amino, alkylamino, aminoalkyl, hydroxy, hydroxyalkyl, alkoxy, alkylthio, phenyloxy, and benzyloxy;
• R16 is selected from C1-C4alkyl and haloC1-C4alkyl;
• and
• p is 0, 1 or 2.