Amidino derivatives and drugs containing the same as the active ingredient

An amidino compound of the formula (I):

• wherein R1 and R2 each independently, is
• 1) hydrogen,
• 2) hydroxy,
• 3) C1-4 alkoxycarbonyl,
• 4) C2-4 alkenyloxycarbonyl,
• 5) C1-4 alkoxycarbonyloxy or
• 6) —COO—(C1-4 alkyl)-phenyl,
• with the proviso that when R1 is group excepting hydrogen, R2 is hydrogen, or when R2 is group excepting hydrogen, R1 is hydrogen
• R3 is
• 1) hydrogen,
• 2) C1-4 alkyl,
• 3) hydroxy,
• 4) —O—(C1-4 alkyl)-phenyl, or
• 5) halogen atom,
• E1 ring is
• 1) 5-7 membered unsaturated carbocyclic ring or
• 2) 5-7 membered unsaturated heterocyclic ring
• E2 ring is
• 1) 5-7 membered unsaturated carbocyclic ring or
• 2) 5-7 membered unsaturated heterocyclic ring;
• E3 ring is
• 1) absent,
• 2) 5-7 membered unsaturated or saturated carbocyclic ring or
• 3) 5-7 membered unsaturated or saturated heterocyclic ring;
• E4 ring is
• 1) 5-6 membered unsaturated carbocyclic ring or
• 2) 5-6 membered unsaturated heterocyclic ring;
• R4 and R5 each independently, is
• 1) —COOR8, in which R8 is hydrogen, C1-8 alkyl, —(C1-4 alkyl)-phenyl or —(C1-4 alkyl)—O—(C1-4 alkyl);
• 2) —(C1-4 alkyl)—COOR9, in which R9 is hydrogen, C1-8 alkyl—(C1-4 alkyl)-phenyl or —(C1-4 alkyl)—O—(C1-4 alkyl);
• 3) —(C2-4 alkenyl)—COOR10, in which R10 is hydrogen, C1-8 alkyl—(C1-4 alkyl)-phenyl or —(C1-4 alkyl)—O—(C1-4 alkyl);
• 4) —O—(C1-4 alkyl)—COOR11, in which R11 is hydrogen, C1-8 alkyl—(C1-4 alkyl)-phenyl or —(C1-4 alkyl)—O—(C1-4 alkyl);
• 5) —CONR12R 13, in which R12 is hydrogen, C1-4 alkyl, R13 is hydroxy, —O—(C1-4 alkyl)-phenyl or cyano;
• 6) —P(O)(OR14)2, in which R14 is hydrogen, C1-4 alkyl or —(C1-4 alkyl)-phenyl;
• or
• 7) tetrazol -5-yl which is optionally substituted by C1-8 alkyl;
• p and q each independently, is 0 or 1-2, with the proviso that p+q is 1 or 2;
• R6 and R7 each independently, is
• 1) hydrogen,
• 2) C1-8 alkyl,
• 3) nitro,
• 4) cyano,
• 5) halogen atom,
• 6) —(C1-4 alkyl)—O—(C1-4 alkyl)-phenyl,
• 7) —NR15R16, in which R15 and R16 each independently, is hydrogen or C1-8 alkyl;
• 8) —OR17, in which R17 is hydrogen, C1-8 alkyl, CF3, C2-5 acyl, —(C1-4 alkyl)-phenyl, —(C1-4 alkyl)—OH, —(C1-4 alkyl)—O—(C1-4 alkyl), or —(C1-4 alkyl)—O—(C1-4 alkyl)—O—(C1-4 alkyl);
• 9) —(C1-4 alkyl)—OR17, in which R17 is as hereinbefore defined;
• 10) —J1-J2, in which J1 is
• (1) —CONR18—, in which R18 is hydrogen or C1-4 alkyl;
• (2) —NR19CO—, in which R19 is hydrogen or C1-4 alkyl;
• (3) —SO2NR20—, in which R20 is hydrogen or C1-4 alkyl;
• (4) —NR21SO2—, in which R21 is hydrogen or C1-4 alkyl;
• (5) —(C1-4 alkyl)—NR22—, in which R22 is hydrogen or C1-4 alkyl;
• (6) —CO—,
• (7) —(C1-4 alkyl)—NR23CO—, in which R23 is hydrogen or C1-4 alkyl;
• J2 is
• (1) C1-15 alkyl optionally substituted by 1-3 of following groups (i)-(x):
• (i) C3-7 cycloalkyl optionally substituted by —(C1-4 alkyl)—OR24;
• (ii) phenyl,
• (iii) 5-7 membered saturated heterocyclic ring optionally substituted by carboxyl or C1-4 alkoxycarbonyl;
• (iv) OR24, in which R24 is hydrogen, C1-4 alkyl, —COO—(C1-4 alkyl)-phenyl, C2-5 acyl, or —(C1-4 alkyl)-phenyl;
• (v) NR25R26, in which R25 is hydrogen or C1-4 alkyl, R26 is hydrogen, C1-4 alkyl, —COO(C1-4 alkyl)-phenyl, imino(C1-4 alkyl) or C1-4 alkoxycarbonyl;
• (vi) —S(O)r—(C1-4 alkyl), in which r is 0-2;
• (vii) —COOR27, in which R27 is hydrogen, C1-4 alkyl or —(C1-4 alkyl)-phenyl;
• (viii) —CONR28R29, in which R28 and R29 each independently, is
• (i) hydrogen, (ii) C1-4 alkyl, (iii) hydroxy, or (iv) C1-4 alkyl substituted by one of hydroxy, phenyl or NR25R26, or R28 and R29 taken together with the nitrogen atom to which they are attached form 5-6 membered saturated heterocyclic ring containing nitrogen atom
• (ix) halogen atom,
• (x) trihalomethyl;
• (2) C2-8 alkenyl,
• (3) C5-7 cycloalkyl optionally substituted by 1-3 of C1-4 alkyl, —COOR27, in which R27 is as hereinbefore defined;
• —(C1-4 alkyl)—OR24, in which R24 is as hereinbefore defined;
• (4) —NR25R26, in which R25 and R26 is as hereinbefore defined;
• (5) 5-6 membered saturated heterocyclic ring optionally substituted by 1-3 of C1-4 alkyl, oxo, imino(C1-4 alkyl);
• or R18 and J2 taken together with the nitrogen atom to which they are attached form saturated heterocyclic ring optionally substituted by 1-3 of C1-8 alkyl, C2-8 alkenyl or —COOR27, in which R27 is as hereinbefore defined;
• m is 1-3;
• n is 1-3;
• two R6 taken together with the neighboring two carbon of E4 ring to which they are attached form 5-6 membered unsaturated carbocyclic ring or 5-6 membered saturated heterocyclic ring, that rings may be substituted by 1-3 of R4 or R6;
• A is
• 1) ethylene,
• 2) vinylene,
• 3) ethynylene,
• 4) —O—CH2—,
• 5) —CH2—O—,
• 6) —NR30CO—, in which R30 is hydrogen or C1-4 alkyl
• 7) —NR31CHR32—, in which R31 is hydrogen or C1-4 alkyl, R32 is hydrogen, cyano, COOR36, in which R36 is hydrogen or C1-4 alkyl;
• or CONR37R38, in which R37 and R38 each independently, is hydrogen or C1-4 alkyl;
• 8) —CH2—NR33—, in which R33 is hydrogen or C1-4 alkyl;
• 9) —S—CH2—,
• 10) —CH2—S—,
• 11) —SO2NR34—, in which R34 is hydrogen or C1-4 alkyl;
• 12) —NR35SO2—, in which R35 is hydrogen or C1-4 alkyl;
• non-toxic salts thereof, or hydrates thereof.