Indole-2-Carboxylic Acid Hydrazides

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is —C(O)—, —S(O)2—, or —C(NH)—;
• Z is C1-4alkylene, oxygen, —(CH2)mO—, —O(CH2)m—, —NR—, —(CH2)mNR—, —NR(CH2)m—, —(CH2)mS(O)2—, or a bond;
• m is 1, 2, 3, or 4;
• R is C0-4alkyl, C0-4alkylaryl, or C0-4alkylhetoraryl;
• R1 and R1′ are each independently, halogen, hydroxy, cyano, C0-4alkyl, C1-4alkoxy, fluoromethyl, difluoromethyl, trifluoromethyl, ethenyl, or ethynyl;
• R2 is C0-4alkyl, COOR6, COR6, C1-4alkoxyC1-4alkyl-, hydroxyC1-4alkyl-, cycloalkylC0-4alkyl-, arylC0-4alkyl-, or hetarylC0-4alkyl-, wherein any of the aryl or hetaryl rings are optionally substituted with 1-2 independent halogen, cyano, C1-4alkyl, C1-4alkoxy, —N(C0-4alkyl)(C0-4alkyl), —SO2C1-4alkyl, —SO2N(C0-4alkyl)(C0-4alkyl), hydroxy, fluoromethyl, difluoromethyl, or trifluoromethyl substituents;
• R3 is hydrogen, —COOC0-4alkyl, C1-4alkoxy, C1-4alkyl, arylC1-4alkylthio-, —C0-4alkylaryl, —C0-4alkylhetaryl, —C0-4alkylcycloalkyl, or —C0-4alkylheterocyclyl, wherein any of the rings is optionally substituted with 1-3 independent halogen, cyano, C1-4alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, —C0-4alkylNHC(O)O(C1-4alkyl), —C0-4alkylNR7R8, —C(O)R9, C1-4alkoxyCO4alkyl-, —COOC0-4alkyl, O—C4alkylNHC(O)R9, —C0-4alkylC(O)N(R10)2, —C1-4alkoxyC1-4alkoxy, hydroxyC0-4alkyl-, —NHSO2R10, —SO2(C1-4alkyl), —SO2NR11R12, 5- to 6-membered heterocyclyl, phenylC0-2alkoxy, or phenylC0-2alkyl substituents, wherein phenyl is optionally substituted with 1-2 independent halogen, cyano, C1-4alkyl, C1-4alkoxy, —N(C0-4alkyl)(C0-4alkyl), —SO2C1-4alkyl, —SO2N(C0-4alkyl)(C0-4alkyl), hydroxy, fluoromethyl, difluoromethyl, or trifluoromethyl substituents, or two bonds on a ring carbon of the heterocyclyl group optionally can form an oxo (═O) substituent;
• or R3 is —NR4(—C0-4alkylR5);
• R4 is C0-3alkyl, —C2-3alkyl-NR7R8, C3-6cycloalkyl optionally substituted by hydroxyC0-4alkyl- further optionally substituted by hydroxy, C1-2alkoxyC2-4alkyl-, or C1-2alkyl-S(O)n—C2-3alkyl-;
• n is 0, 1, or 2;
• R5 is hydrogen, hydroxyC2-3alkyl-, C1-2alkoxyCO4alkyl-, or aryl, hetaryl, or heterocyclyl;
• wherein a heterocyclic nitrogen-containing R5 ring optionally is mono-substituted on the ring nitrogen with C1-4alkyl, benzyl, benzoyl, C1-4alkyl-C(O), —SO2C1-4alkyl, —SO2N(C0-4alkyl)(C0-4alkyl), C1-4alkoxycarbonyl, or aryl(C1-4alkoxy)carbonyl;
• and wherein the R5 rings are optionally mono-substituted on a ring carbon with halogen, cyano, C1-4alkyl-C(O), C1-4alkyl-SO2—, C1-4alkyl, C1-4alkoxy, hydroxy, —N(C0-4alkyl)(C0-4alkyl), hydroxyC0-4alkyl-, or C0-4alkylcarbamoyl-, provided that no quaternised nitrogen is included;
• or two bonds on a ring carbon of the heterocycle optionally can form an oxo (═O) substituent;
• R6 is C1-4alkyl, aryl, or hetaryl;
• R7 and R3 are independently C0-4alkyl, C3-6cycloalkyl, or CO(C1-4alkyl);
• R9 is C1-4alkyl, or C3-6cycloalkyl;
• R10 is C0-4alkyl, or C3-6cycloalkyl;
• and
• R11 and R12 are independently C0-4alkyl or together with the nitrogen to which they are attached may form a 4- to 6-membered heterocycle;
• provided there are no nitrogen-oxygen, nitrogen-nitrogen, oxygen-oxygen or nitrogen-halogen bonds in the grouping —Y-Z-R3;
• and
• provided that when —Y-Z- represents —C(O)—, —C(NH)—, —C(O)—C1-4alkylene, —C(NH)—C1-4alkylene, —C(O)—NR—, —C(NH)—NR—, —C(O)—(CH2)mNR—, or —C(NH)—(CH2)mNR—, then R3 is not optionally substituted C3-10cycloalkyl, C5-10cycloalkenyl, phenyl, naphthyl, pyridyl, pyrazinyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, furanyl, thiophenyl, pyrrolyl, pyrrolidinyl, piperidinyl, indolyl, benzo[1,3]dioxol, thieno[2,3-b]pyrrolyl, or thieno[3,2-b]pyrrolyl.