Patent NZ-711064-A (NZ)
Title: Pyridone-substituted pyrazolyl compounds as serine protease inhibitors
Inventor: SHORT KEVIN
IPC: C07D231/38
Filed: 2014-03-17
Abstract: The invention provides a compound with structure of Formula (V): or pharmaceutically acceptable salt, ester, solvate, or prodrug thereof; wherein L1 is -NR7-; L2 is –C(=O)-; L5 is a bond or substituted or unsubstituted alkylene, provided that if L5 is a bond, R5 is hydrogen; R1 is substituted alkyl; R2 is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted fused ring aryl, or substituted or unsubstituted heteroaryl; R5 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted fused ring aryl, or substituted or unsubstituted heteroaryl; and R7 is hydrogen, or substituted or unsubstituted alkyl; and wherein the term “alkyl” means a straight or branched chain, which can be fully saturated, or mono- or polyunsaturated; and wherein the term “heteroalkyl” means a straight or branched chain, consisting of at least one carbon atom and at least one heteroatom selected from the group consisting of O, N, P, Si, and S; and wherein any substituted group may be substituted with one or more substituent group selected from the following moieties: (A) -OH, -NH2, -SH, -CN, -CF3, -NO2, oxo, halogen, -COOH, unsubstituted C1-C24 alkyl, unsubstituted 2- to 20 membered heteroalkyl, unsubstituted C3-C8 cycloalkyl, unsubstituted C3-C8 cycloalkenyl, unsubstituted 4- to 8-membered heterocycloalkyl, unsubstituted 4- to 8-membered heterocycloalkenyl, unsubstituted aryl, unsubstituted heteroaryl, and (B) C1-C24 alkyl, 2- to 20 membered heteroalkyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, 4- to 8-membered heterocycloalkyl, 4- to 8-membered heterocycloalkenyl, aryl, and heteroaryl, substituted with at least one substituent selected from: (i) oxo, -OH, -NH2, -SH, -CN, -CF3, -NO2, halogen, -COOH, unsubstituted C1- C24 alkyl, unsubstituted 2- to 20 membered heteroalkyl, unsubstituted C3-C8 cycloalkyl, unsubstituted C3-C8 cycloalkenyl, unsubstituted 4- to 8-membered heterocycloalkyl, unsubstituted 4- to 8-membered heterocycloalkenyl, unsubstituted aryl, unsubstituted heteroaryl, and (ii) C1-C24 alkyl, heteroalkyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, 4- to 8- membered heterocycloalkyl, 4- to 8-membered heterocycloalkenyl, aryl, and heteroaryl, substituted with at least one substituent selected from: (a) oxo, -OH, -NH2, -SH, -CN, -CF3, -NO2, halogen, -COOH, unsubstituted C1-C24 alkyl, unsubstituted 2- to 20 membered heteroalkyl, unsubstituted C3-C8 cycloalkyl, unsubstituted C3-C8 cycloalkenyl, unsubstituted 4- to 8-membered heterocycloalkyl, unsubstituted 4- to 8-membered heterocycloalkenyl, unsubstituted aryl, unsubstituted heteroaryl, and (b) C1-C24 alkyl, 2- to 20- membered heteroalkyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, 4- to 8-membered heterocycloalkyl, 4- to 8-membered heterocycloalkenyl, aryl, or heteroaryl, substituted with at least one substituent selected from: oxo, -OH, -NH2, -SH, - CN, -CF3, -NO2, halogen, -COOH, unsubstituted C1-C24 alkyl, unsubstituted 2- to 20 membered heteroalkyl, unsubstituted C3-C8 cycloalkyl, unsubstituted C3-C8 cycloalkenyl, unsubstituted 4- to 8-membered heterocycloalkyl, unsubstituted 4- to 8-membered heterocycloalkenyl, unsubstituted aryl, and unsubstituted heteroaryl. The compounds are useful for the inhibition of serine proteases, such as thrombin and kallikrein. There are additionally provided pharmaceutical compositions including said pyridone-substituted pyrazolyl compounds.