Patent ID: 6337344
Filing Date: 2002-01-08
Classification: A61P,C07D

Abstract:
Compounds of the formula I, whereintwo of the residues R1a, R1b, R1c and R1d independent of one another are hydrogen, F, Cl, Br, I, (C1-C4)-alkyl, CF3, phenyl, phenyl-(C1-C4)-alkyl-, (C1-C4)-alkoxy, phenyloxy-, phenyl-(C1-C4)-alkoxy-, OH, NO2, â€”NR5aR5b, â€”NR5bâ€”SO2â€”R6a, â€”Sâ€”R6b, â€”SOnâ€”R6c where n is 1 or 2, â€”SO2â€”NR5aR5b, â€”CN or â€”COâ€”R7, and are identical or different, and the other two of the residues R1a, R1b, R1c and R1d are hydrogen; R5a is hydrogen, (C1-C4)-alkyl, phenyl, phenyl-(C1-C4)-alkyl-, formyl, ((C1-C4)-alkyl)carbonyl-, phenylcarbonyl-, phenyl-((C1-C4)-alkyl)carbonyl-, ((C1-C4)-alkoxy)carbonyl- or phenyl-((C1-C4)-alkoxy)carbonyl-; R5b is hydrogen, (C1-C4)-alkyl, phenyl or phenyl-(C1-C4)-alkyl-; R6a is (C1-C4)-alkyl, phenyl, phenyl-(C1-C4)-alkyl- or phenyl-NHâ€”; R6b is (C1-C4)-alkyl, phenyl or phenyl-(C1-C4)-alkyl-; R6c is hydroxy, (C1-C4)-alkyl, phenyl or phenyl-(C1-C4)-alkyl-; R7 is hydroxy, (C1-C4)-alkoxy, phenyl-(C1-C4)-alkoxy- or â€”NR5aR5b; where all residues R5a, R5b, R6a, R6b, R6c and R7 if present more than one time in the molecule, are independent of one another and can each be identical or different;and where phenyl present in the residues R1a, R1b, R1c, R1d, R5a, R5b, R6a, R6b, R6c and R7 denotes an unsubstituted phenyl residue or a phenyl residue which is substituted by one or two identical or different substituents selected from the series consisting of (C1-C4)-alkyl, F, Cl, Br, CF3, (C1-C4)-alkoxy, NO2, OH, NH2 and CN; one of the residues R2 and R3 is â€”(CH2)pâ€”COâ€”R8 and the other is hydrogen, F, Cl, Br, (C1-C4)-alkyl or â€”(CH2)pâ€”COâ€”R8, or R2 and R3 together form a group of the formula â€”CH2â€”CH2â€”N(â€”COâ€”R20)â€”CH2â€” wherein R20 is phenyl, phenyl-(C1-C4)-alkyl-, pyridyl or pyridyl-(C1-C4)-alkyl- and where each phenyl residue is unsubstituted or substituted by R15a and each pyridyl residue is unsubstituted or substituted at the nitrogen atom by R14; p is 0, 1 or 2; R8 is â€”NR9R10, â€”OR10 or â€”Sâ€”(C1-C4)-alkyl, where residues R8 if present more than one time in the molecule, are independent of each other and can be identical or different; R9 is hydrogen, (C1-C4)-alkyl-, hydroxycarbonyl-(C1-C4)-alkyl-, ((C1-C4)-alkoxy)carbonyl-(C1-C4)-alkyl- or aminocarbonyl-(C1-C4)-alkyl-; R10 is hydrogen, (C1-C10)-alkyl-, phenyl, naphthyl, phenyl-(C1-C4)-alkyl-, naphthyl-(C1-C4)-alkyl-, pyridyl or the residue Het, where the (C1-C10)-alkyl- residue and each phenyl and naphthyl residue is unsubstituted or substituted by one, two or three identical or different residues R11, and where the pyridyl residue is unsubstituted or substituted at the nitrogen atom by R14, and where Het is unsubstituted or substituted by R15a; or R9 and R10 together with the nitrogen atom to which they are bonded form a 5-membered or 6-membered saturated heterocyclic ring which can contain an additional nitrogen atom in the ring and which is unsubstituted or substituted by R15a or by â€”COâ€”R7; Het is the residue of a 5-membered or 6-membered saturated heterocyclic ring containing 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur; R11 is â€”N(R12)2, â€”OR12, â€”COâ€”N(R13)2, â€”COâ€”R7, R15b, (C1-C14)-alkyl, phenyl which is unsubstituted or substituted by one, two or three identical or different residues R15b, naphthyl which is unsubstituted or substituted by one, two or three identical or different residues R15b, quinolinyl which is unsubstituted or substituted by one, two or three identical or different residues R15b and/or substituted at the nitrogen atom by R14, isoquinolinyl which is unsubstituted or substituted by one, two or three identical or different residues R15b and/or substituted at the nitrogen atom by R14, pyridyl which is unsubstituted or substituted at the nitrogen atom by R14, or Het which is unsubstituted or substituted by R15a, where residues R11 if present more than one time in the molecule, are independent of each other and can be identical or different; each residue R12 independent of the denotation of another residue R12 is hydrogen, (C1-C4)-alkyl, phenyl, phenyl-(C1-C4)-alkyl-, naphthyl, naphthyl-C1-C4)-alkyl-, pyrrolidinyl, piperidinyl, pyrrolidinyl-(C1-C4)-alkyl- or piperidinyl-(C1-C4)-alkyl-, where each pyrrolidinyl residue and each piperidinyl residue is unsubstituted or substituted at the nitrogen atom by phenyl-(C1-C4)-alkyl- or R15a; each residue R13 independent of the denotation of another residue R13 is hydrogen, (C1-C4)-alkyl, phenyl, phenyl-(C1-C4)-alkyl-, naphthyl or naphthyl-(C1-C4)-alkyl-, or the two residues R13 together with the nitrogen atom to which they are bonded form a 5-membered or 6-membered saturated heterocyclic ring which can contain an additional nitrogen atom or oxygen atom in the ring where the additional nitrogen atom in the ring is unsubstituted or substituted by (C1-C4)-alkyl or phenyl-(C1-C4)-alkyl-; R14 is (C1-C6)-alkyl, (C1-C6)-alkenyl, (C1-C6)-alkynyl, phenyl-(C1-C6)-alkyl- or ((C1-C6)-alkoxy)carbonyl-(C1-C5)-alkyl-, where phenyl present in R14 denotes an unsubstituted phenyl residue, the substitution by these residues at the nitrogen atom of the heterocyclic residue leading to a positively charged group having Xâˆ’ as the counterion; or R14 is oxido this substitution at the nitrogen atom of the heterocyclic residue leading to an N-oxide; and where residues R14 if present more than one time in the molecule, are independent of each other and can be identical or different; R15a is (C1-C6)-alkyl, ((C1-C6)-alkyl)-C(&boxH;NH)â€”, â€”(CH2)tâ€”N(R16)2, â€”(CH2)tâ€”N+(R16a)2(â€”Oâˆ’), â€”(CH2)tâ€”N+(R16a)3Xâˆ’, â€”(CH2)tâ€”NHR17, â€”(CH2)tâ€”CN, â€”(CH2)tâ€”CSâ€”N(R18)2, â€”(CH2)tâ€”C(&boxH;NR17)â€”NHR17 or â€”(CH2)tâ€”NHâ€”C(&boxH;NR17)â€”NHR17, where ((C1-C6)-alkyl)-C(&boxH;NH)â€” is bonded to a ring nitrogen atom, and where residues R15a if present more than one time in the molecule, are independent of each other and can be identical or different; R15b is (C1-C6)-alkyl, hydroxy, (C1-C4)-alkoxy, F, Cl, Br, I, NO2, â€”(CH2)tâ€”N(R16)2, â€”(CH2)tâ€”N+(R16a)2(â€”Oâˆ’), â€”(CH2)tâ€”N+(R16a)3Xâˆ’, â€”(CH2)tâ€”NHR17, â€”(CH2)tâ€”COâ€”OR18, â€”(CH2)tâ€”COâ€”N(R18)2, â€”(CH2)tâ€”CN, â€”(CH2)tâ€”CSâ€”N(R18)2, â€”(CH2)tâ€”C(&boxH;NR17)â€”NHR17 or â€”(CH2)tâ€”NHâ€”C(&boxH;NR17)â€”NHR17, where alkyl can be substituted 1, 2, 3, 4, 5, 6, or 7 times by fluoro, and where residues R15b if present more than one time in the molecule, are independent of each other and can be identical or different; t is 0, 1, 2 or 3, where numbers t, if present more than one time in the molecule, are independent of each other and can be identical or different; each residue R16 independent of the denotations of another residue R16 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkenyl, (C1-C6)-alkynyl, phenyl-(C1-C6)-alkyl- or ((C1-C6)-alkoxy)carbonyl-(C1-C6)-alkyl-, where phenyl present in R16 denotes an unsubstituted phenyl residue, and where groups containing residues R16 if present more than one time in the molecule, are independent of each other and can be identical or different; each residue R16a independent of the denotations of another residue R16a is (C1-C6)-alkyl, (C1-C6)-alkenyl, (C1-C6)-alkynyl, phenyl-(C1-C6)-alkyl- or ((C1-C6)-alkoxy)carbonyl-(C1-C6)-alkyl-, where phenyl present in R16a denotes an unsubstituted phenyl residue, and where groups containing residues R16a if present more than one time in the molecule, are independent of each other and can be identical or different; each residue R17 independent of the denotation of another residue R17 is hydrogen, (C1-C6)-alkyl, (C1-C6)-alkylcarbonyl-, (C1-C6)-alkoxycarbonyl-, (C1-C6)-alkylcarbonyloxy-(C1-C6)-alkoxycarbonyl-, phenylcarbonyl-, phenoxycarbonyl-, phenyl-(C1-C6)-alkoxycarbonyl-, hydroxy, (C1-C6)-alkoxy, phenyl-(C1-C6)-alkoxy- or amino, and additionally in the groups â€”(CH2)tâ€”C(&boxH;NR17)â€”NHR17 and â€”(CH2)tâ€”NHâ€”C(&boxH;NR17)â€”NHR17 the two residues R17 together with the C(&boxH;N)â€”NH group to which they are bonded, can form a 5-membered or 6-membered heterocyclic ring, and where phenyl present in R17 denotes an unsubstituted phenyl residue, and where groups containing residues R17 if present more than one time in the molecule, are independent of each other and can be identical or different; each residue R18 independent of the denotation of another residue R18 is hydrogen or (C1-C4)-alkyl; A is a direct linkage, a divalent â€”(C1-C4)-alkyl- residue which is saturated or which contains a double bond or a triple bond, â€”COâ€”, â€”SOrâ€” wherein r is 1 or 2, â€”COâ€”(C1-C4)-alkyl-, â€”(C1-C4)-alkyl-COâ€” or â€”(C1-C4)-alkyl-COâ€”NHâ€” wherein the nitrogen is bonded to R4; R4 is phenyl which is substituted by one residue R15c and which can additionally be substituted by one or two substituents from the series consisting of (C1-C4)-alkyl, F, Cl and Br, or R4 is pyridyl which is unsubstituted or substituted at the nitrogen atom by R14, or R4 is the residue Het which is substituted by R15d; R15c is â€”(CH2)tâ€”N(R16)2, â€”(CH2)tâ€”N+(R16a)2(â€”Oâˆ’), â€”(CH2)tâ€”N+(R16a)3Xâˆ’, â€”(CH2)tâ€”NHR17, â€”(CH2)tâ€”CN, â€”(CH2)tâ€”CSâ€”N(R18)2, â€”(CH2)tâ€”C(&boxH;NR17)â€”NHR17 or â€”(CH2)tâ€”NHâ€”C(&boxH;NR17)â€”NHR17; R15d is ((C1-C6)-alkyl)-C(&boxH;NH)â€”, â€”(CH2)tâ€”N(R16)2, â€”(CH2)tâ€”N+(R16a)2(â€”Oâˆ’), â€”(CH2)tâ€”N+(R16a)3Xâˆ’, â€”(CH2)tâ€”NHR17, â€”(CH2)tâ€”CN, â€”(CH2)tâ€”CSâ€”N(R18)2, â€”(CH2)tâ€”C(&boxH;NR17)â€”NHR17 or â€”(CH2)tâ€”NHâ€”C(&boxH;NR17)â€”NHR17, where ((C1-C6)-alkyl)-C(&boxH;NH)â€” is bonded to a ring nitrogen atom; Xâˆ’ is a physiologically acceptable anion; in all their stereoisomeric forms and mixtures thereof in any ratio, and their physiologically acceptable salts.