5-amidino-n-(2-aminophenethyl)-n-hydroxy-benzenesulffonamide derivative, medical composition containing the same, pharmaceutical use thereof and intermediate therefor

A 5-amidino-N-(2-aminophenethyl)-2-hydroxybenzenesulfonamide derivative represented by the general formula:

• wherein R1 represents a hydrogen atom or a lower alkyl group;
• R2 represents a hydrogen atom, a lower alkyl group, —Y—COORA in which Y1 represents a lower alkylene group or a single bond;
• and RA represents a hydrogen atom or a lower alkyl group, —COCOORB in which RB represents a hydrogen atom or a lower alkyl group, —Y2—CONH—RC in which Y2 represents a lower alkylene group or a single bond;
• and RC represents a hydrogen atom, or a lower alkyl group which may have a substituent selected from the following group (i), —COCONH—RD in which RD is a hydrogen atom or a lower alkyl group which may have a substituent selected from the following group (ii), —CO—Y3—RE in which Y3 is a lower alkylene group or a single bond;
• and RE represents a 5 to 10-membered aromatic heterocyclic group which may have a lower alkyl group, —CO—Y4—RF in which Y4 is a lower alkylene group which may have one or two hydroxy groups;
• and RF represents a —COORF1 in which RF1 is a hydrogen atom or a lower alkyl group, or a lower alkylsulfonyl group which may have —COORG where RG is a hydrogen atom or a lower alkyl group;
• (i) —COORC1 in which RC1 is a hydrogen atom or a lower alkyl group;
• (ii) —COORD1 in which RD1 is a hydrogen atom or a lower alkyl group;
• R3 represents a di(lower alkyl)amino group, a lower alkyl group, a 3 to 10-membered cycloalkyl group, a 6 to 10-membered aryl group which may have one to three substituents selected from the following group (A), a 3 to 10-membered heterocycloalkyl group which may have an oxo group, or a 5 to 10-membered aromatic heterocyclic group which may have a substituent selected from the following group (B);
• (A) an oxo group, a lower alkyl group, a halo(lower alkyl)group, —Y5—RH, a halogen atom, a nitro group, an amino group, —COOR1, a carbamoyl group, a sulfamoyl group, a lower alkylsulfonyl group, a mono(lower alkyl)sulfamoyl group which may have —COORJ, and a lower alkylsulfonylamino-substituted (lower alkyl) group;
• wherein Y5 represents an oxygen atom or a sulfur atom;
• RH represents a hydrogen atom, a halo(lower alkyl)group or a lower alkyl group which may have —COORH1 in which RH1 is a hydrogen atom, a 3 to 10-membered heterocycloalkyl group or a lower alkyl group;
• R1 represents a hydrogen atom, a 3 to 10-membered cycloalkyl group or a lower alkyl group;
• RJ represents a hydrogen atom, a 3 to 10-membered cycloalkyl group or a lower alkyl group;
• (B) a lower alkyl group, an amino group and —COORK;
• wherein RK represents a hydrogen atom, a 3 to 10-membered cycloalkyl group and lower alkyl group;
• Q represents a hydrogen atom or a lower alkyl group which may have a substituent selected from the following group (C);
• (C) —ORL, —COORM, —CONRNRO, a 6 to 10-membered aryl group which may have one to three substituents selected from the following group (iii), and a 5 to 10-membered aromatic heterocyclic group which may have one to three substituents selected from the following group (iv);
• wherein RL represents a hydrogen atom or a lower alkyl group which may have —ORL1 where RL1 represents a hydrogen atom or a lower alkyl group;
• RM represents a hydrogen atom, a 3 to 10-membered cycloalkyl group, or a lower alkyl group which may have a substituent selected from the following group (v);
• RN and RO independently represent a hydrogen atom, a 6 to 10-membered aryl group which may have a carbamoyl group, a 5 to 10-membered aromatic heterocyclic group which may have a substituent selected from the following group (vi), or a lower alkyl group which may have a substituent selected from the following group (vii), or —NRNRO forms a cyclic amino group which may have a substituent selected from the following group (viii);
• (v) —COORM1 in which RM1 is a hydrogen atom, a 3 to 10-membered cycloalkyl group or a lower alkyl group, —OCORM2 in which RM2 is a 3 to 10-membered cycloalkyl group or a lower alkyl group, —OCOORM3 in which RM3 is a 3 to 10-membered cycloalkyl group or a lower alkyl group, —ORM4 in which RM4 is a hydrogen atom, a 3 to 10-membered cycloalkyl group or a lower alkyl group, —CONRM5RM6 in which RM5 and RM6 are independently a hydrogen atom or a lower alkyl group, or —NRM5RM6 forms a cyclic amino group, a 3 to 10-membered cycloalkyl group, a 6 to 10-membered aryl group, a 3 to 10 membered heterocycloalkyl group, and a 5 to 10-membered aromatic heterocyclic group;
• (vi) a halogen atom, a lower alkyl group, a carbamoyl group and —COORN1 in which RN1 represents a hydrogen atom, or a lower alkyl group;
• (vii) —ORN2 in which RN2 is a hydrogen atom or a lower alkyl group, and a 5 to 10-membered aromatic heterocyclic group;
• (viii) a hydroxy group, a lower alkyl group, a hydroxy(lower alkyl) group, a carbamoyl group, a di(lower alkyl)amino group, a lower acyl group, and —COORN3 in which RN3 represents a hydrogen atom or a lower alkyl group;
• (iii) a halogen atom, a nitro group, a lower alkyl group, —ORP in which RP is a hydrogen atom or a lower alkyl group, and —COORQ in which RQ is a hydrogen atom or a lower alkyl group;
• (iv) a halogen atom, an oxo group, a lower alkyl group and a phenyl group;
• and Z represents a hydrogen atom, a hydroxy group or —COORR;
• wherein RR is a halo(lower alkyl) group, a 6 to 10-membered aryl group or a lower alkyl group which may have a substituent selected from the following group (ix);
• (ix) —ORR1 in which RR1 is a hydrogen atom or a lower alkyl group, —COOR2 in which RR2 is a lower alkyl group which may have —COORR21 where RR21 is a lower alkyl group, —CONRR3RR4 in which RR3 and RR4 are independently a hydrogen atom or a lower alkyl group, or —NRR3RR4 forms a cyclic amino group, —OCORR5 in which RR5 is a lower alkyl group which may have —OCORR51 where RR51 is a lower alkyl group, a 3 to 10-membered heterocycloalkyl group and a 6 to 10-membered aryl group;
• or a pharmaceutically acceptable salt thereof.