GUANIDINOBENZOIC ACID COMPOUND

摘要

[Problem];Provided is a compound which is useful as an agent for preventing and/or treating renal diseases. [Means for Solution];The present inventors have conducted extensive studies on compounds having a trypsin inhibitory action, and as a result, they have found that a guanidinobenzoic acid compound has a trypsin inhibitory action, thereby completing the present invention. The guanidinobenzoic acid compound of the present invention can be used as an agent for preventing and/or treating renal disease as an agent which will substitute low-protein diet therapy, and an agent for preventing and/or treating trypsin-related diseases, for example, pancreatitis, gastroesophageal reflux disease, hepatic encephalopathy, influenza, and the like.

主权项

1. A compound of formula (I) or a salt thereof: wherein Ring A is of formula (a), (b), or (c); each R1 is independently a lower alkyl, halogen, or —OH, R2 is H; lower alkyl optionally substituted with at least one substituent selected from the group consisting of halogen, —CO2H, —OH, —O-lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aromatic heterocycle, and optionally substituted non-aromatic heterocycle; optionally substituted cycloalkyl; optionally substituted aryl; optionally substituted aromatic heterocycle; optionally substituted non-aromatic heterocycle; or optionally substituted —C(O)-lower alkylene-aryl, L1 is —Y1-lower alkylene-Y2— or —C(O)—N(R6)—, or if Ring A is of formula (b) or formula (c), then L1 is optionally —C(O)—, L2 is a lower alkylene optionally substituted with at least one substituent selected from the group consisting of halogen, —CO2H, —OH, —O-lower alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aromatic heterocycle, and optionally substituted non-aromatic heterocycle; Y3-cyclohexanediyl-Y4—; or —Y3-phenylene-Y4—, and L2 is optionally combined with the nitrogen atom bonded thereto and the R2 group on the nitrogen atom to form an optionally substituted cyclic amino, R3 is H or lower alkyl optionally substituted with halogen, —OH, —O-lower alkyl, cycloalkyl, aryl, aromatic heterocycle or non-aromatic heterocycle, provided that if -L2-N(R2)-L1-is —(CH2)n—NH—C(O)—(CH2)n—, —CH(—Rz)—NH—C(O)—(CH2)n—, or —(CH2)r-phenylene-NH—C(O)—(CH2)n— wherein each n is independently an integer of from 0 to 5, r is 0 or 1, Rz is —CH2—C(O)—OCH3 or benzyl optionally substituted with at least one selected from the group consisting of halogen, nitro, lower alkyl, —OH and —O-lower alkyl, then R3 is a group other than H, each R4 is independently a lower alkyl optionally substituted with halogen, —OH, —O-lower alkyl, cycloalkyl, aryl, aromatic heterocycle, or non-aromatic heterocycle, R5 is H or lower alkyl, R6 is H or lower alkyl, X1, X2 and X3 are each independently CH or N, provided that at least one of X1, X2 and X3 is N, Y1 is a bond or —C(O)—, Y2 is a bond, —N(R6)—, or —C(O)—N(R6)—, each Y3 is independently a bond or lower alkylene, each Y4 is independently a bond, lower alkylene, or —C(O)—, m is an integer of from 0 to 4, p is an integer of from 0 to 3, and q is an integer of from 0 to 4.