Patent ID: 6500811
Filing Date: 2002-12-31
Classification: A61P,C07F

Abstract:
A compound of formula I a stereoisomeric form thereof, or a physiologically tolerable salt thereof, where(A.) R1 is 1. phenyl; 2. phenyl, which is mono- or disubstituted by 2.1. (C1-C6)-alkyl, 2.2. hydroxyl, 2.3. (C1-C6)-alkyl-C(O)â€”Oâ€”, 2.4. (C1-C6)-alkyl-Oâ€”, 2.5. (C1-C6)-alkyl-Oâ€”(C1-C4)-alkyl-Oâ€”, 2.6. halogen, 2.7. â€”CF3, 2.8. â€”CN, 2.9. â€”NO2, 2.10. HOâ€”C(O)â€”, 2.11. (C1-C6)-alkyl-Oâ€”C(O)â€”, 2.12. methylenedioxo, 2.13. R4â€”(R5)Nâ€”C(O)â€”, 2.14. R4â€”(R5)Nâ€”, or 2.15 a residue described under A.3.1 to A.3.16; 3. a residue described under A.3.1 to A.3.16, which is unsubstituted or substituted by one or more radicals described under A.2.1 to A.2.15, 3.1. pyrrole, 3.2. pyrazole, 3.3. imidazole, 3.4. triazole, 3.5. thiophene, 3.6. thiazole, 3.7. oxazole, 3.8. isoxazole, 3.9. pyridine, 3.10. pyrimidine, 3.11. pyrrolidine, 3.12. indole, 3.13. benzothiophene, 3.14. benzimidazole, 3.15. benzoxazole, or 3.16. benzothiazole; or 4. â€”Oâ€”(C1-C6)-alkyl; (B1.) R2 is 1. a hydrogen atom; 2. (C1-C6)-alkyl-; 3. HOâ€”C(O)â€”(C1-C6)-alkyl-; 4. phenyl-(CH2)nâ€”, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, or is substituted by â€”NHâ€”C(O)â€”(C1-C3)-alkyl, and n is the integer zero, 1, or 2; or 5. picolyl; (B2.) R4 and R5 independently of one another are identical or different and are 1. a hydrogen atom; 2. (C1 -C6)-alkyl-; 3. HOâ€”C(O)â€”(C1-C6)-alkyl-; 4. phenyl-(CH2)nâ€”, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, or is substituted by â€”NHâ€”C(O)â€”(C1-C3)-alkyl, and n is the integer zero, 1, or 2; 5. picolyl; or 6. R4 and R5, together with the nitrogen to which they are bonded, form a 4- to 7-membered ring, and the ring is unsubstituted, or a carbon atom in the ring is replaced by â€”Oâ€”, â€”Sâ€”, or â€”NHâ€”, or two adjacent carbon atoms of the 4- to 7-membered ring are part of a benzyl radical; (C.) R and R3 are identical or different and are 1. a hydrogen atom; 2. (C1-C10)-alkyl-, in which alkyl is unsubstituted or monosubstituted by â€”OH; 3. (C2-C10)-alkenyl-, in which alkenyl is linear or branched; 4. R2â€”Oâ€”(C1-C6)-alkyl-; 5. R2â€”S(O)nâ€”(C1-C6)-alkyl-, where n is the integer zero, 1, or 2; 6. R2â€”S(O)(&boxH;NH)â€”(C1-C6)-alkyl-; 7. a radical of formula IIo in which n is the integer zero, 1, or 2, and W is a nitrogen, oxygen, or sulfur atom;8. phenyl-(CH2)mâ€”, in which m is the integer zero,1, 2, 3, 4, 5, or 6, wherein the â€”(CH2)mâ€” chain is unsubstituted or monosubstituted by â€”OH, and wherein phenyl is unsubstituted or mono- or disubstituted by 8.1 radicals described under A.2.1 to A.2.15, 8.2 â€”Oâ€”(CH2)m-phenyl, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, and m is the integer zero, 1, 2, 3, 4, 5, or 6, 8.3 â€”C(O)â€”(CH2)m-phenyl, in which phenyl is defined under C.8.2; 9. residue-(CH2)mâ€”, in which residue is defined under A.3.1 to A.3.16, m is defined under C.8, the â€”(CH2)mâ€” chain is unsubstituted or monosubstituted by â€”OH, and residue is unsubstituted or mono- or disubstituted by 9.1 radicals described under A.2.1 to A.2.15, 9.2 â€”CH(O), 9.3 â€”SO2-phenyl, in which phenyl is unsubstituted or substituted as defined under C.8.2 or C.8.3, 9.4 â€”Oâ€”(CH2)m-phenyl; 10. â€”(CH2)mâ€”P(O)(OH)â€”(C1-C3)-alkyl, in which m is defined under C.8; 11. a characteristic radical of an amino acid; 12. R6â€”C(O)â€”(C0-C6)-alkyl- in which R6 is 12.1. a hydrogen atom, 12.2. (C1-C6)-alkyl-, 12.3. phenyl, which is unsubstituted or substituted with one or more radicals described under A.2.1 to A.2.15, 12.4. residue, which is defined under A.3.1 to A.3.16, and is unsubstituted or substituted with one or more radicals described under A.2.1 to A.2.15, or is substituted by â€”(C1-C4)-alkyl-COOH, 12.5. â€”OH, 12.6. â€”OR2, in which R2 has the meaning described under B1.1 to B1.5, 12.7. â€”NR4â€”(R5), in which R4 and R5 are defined under B2.1 to B2.6, 12.8. residue-(CH2)mâ€”NHâ€”, in which residue is defined under A.3.1 to A.3.16, and is unsubstituted or substituted with one or more radicals described under A.2.1 to A.2.15, and m is defined under C.8, 12.9. R4â€”(R5)Nâ€”NHâ€”, in which R4 and R5 are defined under B2.1 to B2.6, 12.10. HOâ€”C(O)â€”CH(R3)â€”NHâ€”, in which R3 is defined under C.1 to C.11; 13. â€”(CH2)pâ€”N(R9)(R10), in which p is an integer zero, 1, 2, 3, or 4, in which R9 and R10 are identical or different and are 13.1. a hydrogen atom, 13.2. phenyl-(CH2)mâ€”, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, and m is the integer zero, 1, 2, or 3, 13.3. Rxâ€”C(O)â€”, in which Rx is 3.1 (C1-C6)-alkyl-, 3.2 (C2-C6)-alkenyl-, 3.3 phenyl-(CH2)mâ€”, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, and m is the integer zero, 1, 2, or 3, or 3.4 residue-(CH2)mâ€”, in which residue is defined under A.3.1 to A.3.16, 13.4. Rxâ€”Oâ€”C(O)â€”, in which Rx is defined under C.13.3, 13.5. Rxâ€”CH(NH2)â€”C(O)â€”, in which Rx is defined under C.13.3, 13.6. R8â€”N(R7)â€”C(O)â€”, in which R8 is 6.1 a hydrogen atom 6.2 (C1-C6)-alkyl-, 6.3 phenyl-(CH2)m, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, and m is the integer zero, 1, 2, or 3, or 6.4 residue-(CH2)m, in which residue is defined under A.3.1 to A.3.16, and is unsubstituted or substituted with one or more radicals described under A.2.1 to A.2.15, m is the integer zero, 1, 2, or 3, and in which R7 is a hydrogen atom or (C1-C6)-alkyl-, or in which R7 and R8, together with the nitrogen atom to which they are bonded, form a 4- to 7-membered ring, and the ring is unsubstituted or a carbon atom in the ring is replaced by â€”Oâ€”, â€”Sâ€”, or â€”NHâ€”, 13.7. Rxâ€”SO2â€”, in which Rx is defined under C.13.3, 13.8. Rxâ€”NHâ€”C(&boxH;NR7)â€”, in which Rx is defined under C.13.3and R7 is defined under C.13.6.4, or Rx and R7 are 8.1 (C1-C6)-alkyl-C(O)â€”, 8.2 â€”NO2 or 8.3 â€”SO2(CH2)q-phenyl, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, and q is the integer zero, 1, 2, or 3, 13.9. â€”SO2â€”(CH2)q-phenylâ€”phenyl, in which each phenyl independently is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, and q is the integer zero, 1, 2, or 3, or 13.10. a radical of formula IIp in which m is the integer zero, 1, 2, or 3, and W is a nitrogen atom or sulfur atom, or R9 and R10, together with the nitrogen atom to which they are bonded, form a ring chosen from radicals of the subformulae IIa to IIn, where r is the integer 1 or 2, R11 is a radical described under A.2.1 to A.2.15, R7 is defined under C.13.6.4, and m is defined under C.13.2, and a carbon atom in the ring is replaced by zero or one heterospecies chosen from oxygen, sulfur, or nitrogen atom which is unsubstituted or monosubstituted with R2; 14. â€”OH; 15. &boxH;O; 16. (C1-C6)-alkyl-; or in the compound of formula I, a â€”C(R)(R3)â€” radical is optionally replaced by â€”NHâ€”or â€”NR2â€” in which R2 is defined under B1.1 to B1.5;(D.) t is an integer 1, 2, 3, or 4; (E.) alternatively, R2 and R3 together form a ring with an exocyclic phosphinic or phosphonic acid radical of the subformula II in which r is the integer zero, 1, 2, or 3, and one carbon atom in the ring of the radical of subformula II is replaced by zero or one heterospecies chosen from â€”Oâ€”, â€”Sâ€”, or â€”(R7)Nâ€”, in which R7 is 1. a hydrogen atom; 2. (C1-C6)-alkyl; 3. phenyl, in which phenyl is unsubstituted or substituted with one or more radicals described under A.2.1 to A.2.15; 4. benzyl, in which benzyl is unsubstituted or substituted with one or more radicals described under A.2.1 to A.2.15; or 5. R2Nâ€”C(&boxH;NH)â€” where R2 has the meaning described under B1.1 to B1.5, and the carbon atoms in the ring of the subformula II are unsubstituted or mono- or polysubstituted by (C1-C6)-alkyl-, phenyl-, phenyl-(CH2)mâ€” or HOâ€”, or combinations thereof; (F.) U is â€”SO2â€” or â€”COâ€”; (G.) Y1 is a) a hydrogen atom; b) â€”OH; c) â€”(C1-C4)-alkyl, in which alkyl is linear or branched; d) â€”(CH2)u-phenyl, in which u is zero or 1; e) â€”Oâ€”(C1-C4-alkyl, in which alkyl is linear or branched; or f) â€”Oâ€”(CH2)s-phenyl, in which s is zero or 1; Y2 is a) a hydrogen atom; b) â€”OH; c) â€”(C1-C4)-alkyl, in which alkyl is linear or branched; d) â€”(CH2)u-phenyl, in which u is zero or 1; e) â€”Oâ€”(C1-C4)-alkyl, in which alkyl is linear or branched; or f) â€”Oâ€”(CH2)s-phenyl, in which s is zero or 1; with the proviso that Y1 cannot be â€”OH while simultaneously Y2 is â€”(C1-C4)-alkyl, in which alkyl is linear or branched; and that Y2 cannot be â€”OH while simultaneously Y1 is â€”(C1-C4)-alkyl, in which alkyl is linear or branched;(H.) A is a) a covalent bond; b) â€”Oâ€”; c) â€”CH&boxH;CHâ€”; or d) â€”Câ‰¡Câ€”; (I.) B is â€”(CH2)mâ€”, in which m is defined under C.13.2; â€”Oâ€”(CH2)p, in which p is an integer from 1 to 5; or â€”CH&boxH;CHâ€”; and (J.) X is an oxygen atom, or a sulfur atom.