Patent ID: 6235727
Filing Date: 2001-05-22
Classification: A61P,C07F

Abstract:
A compound of formula I ##STR42##a stereoisomeric form thereof, or a physiologically tolerable salt thereof, where(A.) R.sup.1 is1. phenyl;2. phenyl, which is mono- or disubstituted by2.1 (C.sub.1 -C.sub.6)-alkyl,2.2 hydroxyl,2.3. (C.sub.1 -C.sub.6)-alkyl-C(O)--O--,2.4. (C.sub.1 -C.sub.6)-alkyl-O--,2.5. (C.sub.1 -C.sub.6)-alkyl-O-(C.sub.1 -C.sub.4)-alkyl-O--,2.6. halogen,2.7. --CF.sub.3,2.8. --CN,2.9. --NO.sub.2,2.10. HO--C(O)--,2.11. (C.sub.1 -C.sub.6)-alkyl-O--C(O)--,2.12. methylenedioxo,2.13. R.sup.4 --(R.sup.5)N--C(O)--,2.14. R.sup.4 --(R.sup.5)N--, or2.15 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, or3.16. benzothiazole; or4. --O-(C.sub.1 -C.sub.6)-alkyl;(B1.) R.sup.2 is1. a hydrogen atom;2. (C.sub.1 -C.sub.6)-alkyl-;3. Phenyl-(CH.sub.2).sub.n --, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, or is substituted by --NH--C(O)-(C.sub.1 -C.sub.3)-alkyl, and n is the integer zero, 1, or 2; or4. picolyl;(B2.) R.sup.4 and R.sup.5 independently of one another are identical or different and are1. a hydrogen atom;2. (C.sub.1 -C.sub.6)-alkyl-;3. HO--C(O)-(C.sub.1 -C.sub.6)-alkyl-;4. phenyl-(CH.sub.2).sub.n --, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.15, or is substituted by --NH--C(O)-(C.sub.1 -C.sub.3)-alkyl, and n is the integer zero, 1, or 2;5. picolyl; or6. R.sup.4 and R.sup.5, 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 --O--, --S--, or --NH--, or two adjacent carbon atoms of the 4- to 7-membered ring are part of a benzyl radical;(C.) R and R.sup.3 are identical or different and are1. a hydrogen atom;2. (C.sub.1 -C.sub.10)-alkyl-, in which alkyl is unsubstituted or monosubstituted by --OH;3. (C.sub.2 -C.sub.10)-alkenyl-, in which alkenyl is linear or branched;4. R.sup.2 --O-(C.sub.1 -C.sub.6)-alkyl-;5. R.sup.2 --S(O).sub.n -(C.sub.1 -C.sub.6)-alkyl-, where n is the integer zero, 1, or 2;6. R.sup.2 --S(O)(.dbd.NH)-(C.sub.1 -C.sub.6)-alkyl-;7. a radical of formula IIo ##STR43##in which n is the integer zero, 1, or 2, and W is a nitrogen, oxygen, or sulfur atom;8. phenyl-(CH.sub.2).sub.m --, in which m is the integer zero,1, 2, 3, 4, 5, or 6, wherein the --(CH.sub.2).sub.m -- chain is unsubstituted or monosubstituted by --OH, and wherein phenyl is unsubstituted or mono- or disubstituted by8.1 radicals described under A.2.1 to A.2.15,8.2 --O--(CH.sub.2).sub.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 --C(O)--(CH.sub.2).sub.m -phenyl, in which phenyl is defined under C.8.2;9. residue-(CH.sub.2).sub.m --, in which residue is defined under A.3.1 to A.3.16, m is defined under C.8, the --(CH.sub.2).sub.m -- chain is unsubstituted or monosubstituted by --OH, and residue is unsubstituted or mono- or disubstituted by9.1 radicals described under A.2.1 to A.2.15,9.2 --CH(O),9.3 --SO.sub.2 -phenyl, in which phenyl is unsubstituted or substituted as defined under C.8.2 or C.8.3,9.4 --O--(CH.sub.2).sub.m -phenyl;10. --(CH.sub.2).sub.m --P(O)(OH)-(C.sub.1 -C.sub.3)-alkyl, in which m is defined under C.8;11. a characteristic radical of an amino acid;12. R.sup.6 --C(O)-(C.sub.0 -C.sub.6)-alkyl- in which R.sup.6 is12.1. a hydrogen atom,12.2. (C.sub.1 -C.sub.6)-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 -(C.sub.1 -C.sub.4)-alkyl-COOH,12.5. --OH,12.6. --OR.sup.2, in which R.sup.2 has the meaning described under B1.1 to B1.4,12.7. --NR.sup.4 --(R.sup.5), in which R.sup.4 and R.sup.5 are defined under B2.1 to B2.6,12.8. residue-(CH.sub.2).sub.m --NH--, 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. R.sup.4 --(R.sup.5)N--NH--, in which R.sup.4 and R.sup.5 are defined under B2.1 to B2.6,12.10. HO--C(O)--CH(R.sup.3)--NH--, in which R.sup.3 is defined under C.1 to C.11;13. --(CH.sub.2).sub.p --N(R.sup.9)(R.sup.10), in which p is an integer zero, 1, 2, 3, or 4, in which R.sup.9 and R.sup.10 are identical or different and are13.1. a hydrogen atom,13.2. phenyl-(CH.sub.2).sub.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 3,13.3. R.sup.x --C(O)--, in which R.sup.x is3.1 (C.sub.1 -C.sub.6)-alkyl-,3.2 (C.sub.2 -C.sub.6)-alkenyl-,3.3 phenyl-(CH.sub.2).sub.m --, in which phenyl is unsubstituted or mono- or disubstituted with radicals described under A.2.1 to A.2.1 115, and m is the integer zero, 1, 2, or 3, or3.4 residue-(CH.sub.2).sub.m --, in which residue is defined under A.3.1 to A.3.16,13.4. R.sup.x --O--C(O)--, in which R.sup.x is defined under C.13.3,13.5. R.sup.x --CH(NH.sub.2)--C(O)--, in which R.sup.x is defined under C.13.3,13.6. R.sup.8 --N(R.sup.7)--C(O)--, in which R.sup.8 is6.1 a hydrogen atom6.2 (C.sub.1 -C.sub.6)-alkyl-,6.3 phenyl-(CH.sub.2).sub.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, or6.4 residue-(CH.sub.2).sub.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 R.sup.7 is a hydrogen atom or (C.sub.1 -C.sub.6)-alkyl-, or in which R.sup.7 and R.sup.8, 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 --O--, --S--, or --NH--,13.7. R.sup.x --SO.sub.2 --, in which R.sup.x is defined under C.13.3,13.8. R.sup.x --NH--C(.dbd.NR.sup.7)--, in which R.sup.x is defined under C.13.3 and R.sup.7 is defined under C.13.6.4, or R.sup.x and R.sup.7 are8.1 (C.sub.1 -C.sub.6)-alkyl-C(O)--,8.2 --NO.sub.2 or8.3 --SO.sub.2 --(CH.sub.2).sub.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. --SO.sub.2 --(CH.sub.2).sub.q -phenyl-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, or13.10. a radical of formula IIp ##STR44##in which m is the integer zero, 1, 2, or 3, and W is a nitrogen atom or sulfur atom, orR.sup.9 and R.sup.10, together with the nitrogen atom to which they are bonded, form a ring chosen from radicals of the subformulae IIa to IIn, ##STR45## ##STR46##where r is the integer 1 or 2, R.sup.11 is a radical described under A.2.1 to A.2.15, R.sup.7 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 R.sup.2 ;14. --OH;15. .dbd.O;16. (C.sub.1 -C.sub.6)-alkyl-; orin the compound of formula I, a --C(R)(R.sup.3)-- radical is optionally replaced by --NH-- or --NR.sup.2 -- in which R.sup.2 is defined under B1.1 to B1.4;(D.) t is an integer 1, 2, 3, or 4;(E.) alternatively, R.sup.2 and R.sup.3 together form a ring with an exocyclic phosphinic or phosphonic acid radical of the subformula II ##STR47##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 --O--, --S--, or --(R.sup.7)N--, in which R.sup.7 is1. a hydrogen atom;2. (C.sub.1 -C.sub.6)-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; or5. R.sup.2 N--C(.dbd.NH)-- where R.sup.2 has the meaning described under B1.1 to B1.4, and the carbon atoms in the ring of the subformula II are unsubstituted or mono- or polysubstituted by (C.sub.1 -C.sub.6)-alkyl-, phenyl-, phenyl-(CH.sub.2).sub.m -- or HO--, or combinations thereof;(F.) U is --SO.sub.2 --;(G.) Y.sup.1 is --OH and Y.sup.2 isa) a hydrogen atom;b) --OH;c) --(CH.sub.2).sub.u -phenyl, in which u is zero or 1;d) --O-(C.sub.1 -C.sub.4)-alkyl, in which alkyl is linear or branched; ore) --O-(CH.sub.2).sub.s -phenyl, in which s is zero or 1;(H.) A isa) a covalent bond;b) --O--;c) --CH.dbd.CH--; ord) --C.tbd.C--;(I.) B isa) --(CH.sub.2).sub.m --, in which m is defined under C.13.2;b) --O--(CH.sub.2).sub.p, in which p is an integer from 1 to 5; orc) --CH.dbd.CH--; and(J.) X is --CH.dbd.CH--.