Substituted amides, their preparation and use
View Patent ↗An amide of the formula I and its tautomeric forms, possible enantiomeric and diastereomeric forms, E and Z forms, and possible physiologically tolerated salts, in which the variables have the following meanings: A —(CH 2 ) p —R 1 , where R 1 can be pyrrolidine [sic], morpholine [sic], piperidine [sic], —NR 5 R 6 and and R 5 , R 6 and R 7 can, independently of one another, be hydrogen, C 1 -C 4 -alkyl, CH 2 Ph, Ph, CH 2 CH 2 Ph, it also being possible for the phenyl rings to be substituted by R 6 , and p can be 1 and 2, and B can be phenyl [sic], pyridyl [sic], pyrimidyl [sic] and pyridazyl [sic], it also being possible for the rings to be substituted by up to 2 R 8 radicals, and D can be a bond, —(CH 2 ) m —, —CH═CH—, —C≡C—, and R 2 is chlorine, bromine, fluorine, C 1 -C 6 -alkyl, NHCO—C 1 -C 4 -alkyl, NHSO 2 —C 1 -C 4 -alkyl, NO 2 , —O—C 1 -C 4 -alkyl and NH 2 , and R 3 is —C 1 -C 6 -alkyl, branched or unbranched, and which may also carry a phenyl ring, indolyl ring or cyclohexyl ring which is in turn substituted by by [sic] a maximum of two R 8 radicals, where R 8 is hydrogen, C 1 -C 4 -alkyl, branched or unbranched, —O—C 1 -C 4 -alkyl, OH, Cl, F, Br, I, CF 3 , NO 2 , NH 2 , CN, COOH, COO—C 1 -C 4 -alkyl, NHCO—C 1 -C 4 -alkyl, —NHSO 2 -C 1 -C 4 -alkyl and —SO 2 —C 1 -C 4 -alkyl; and Y is phenyl [sic], pyridine, pyrimidine and pyrazine and R 4 is hydrogen, COOR 9 and CO-Z in which Z is NR 10 R 11 and R 9 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and R 10 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which itself may also be substituted by one or two R 12 radicals, and R 11 is hydrogen, C 1 -C 6 -alkyl, branched or unbranched, which may also be and [sic] substituted by a phenyl ring which may also carry an R 9 radical, and R 12 can be hydrogen, C 1 -C 4 -alkyl, branched or unbranched, —O—C 1 -C 4 -alkyl, OH, Cl, F, Br, J, CF 3 , NO 2 , NH 2 , CN, COOH, COO—C 1 -C 4 -alkyl, —NHCO—C 1 -C 4 -alkyl, —NHCO-phenyl, —NHSO 2 —C 1 -C 4 -alkyl, NHSO 2 -phenyl, —SO 2 —C 1 -C 4 -alkyl and —SO 2 -phenyl, R 13 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and R 14 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and n is a number 0, 1 or 2, and m, q are, independently of one another, a number 0, 1, 2, 3 or 4.
1. An amide of the formula I
and its tautomeric forms, enantiomeric and diastereomeric forms, E and Z forms, and possible physiologically tolerated salts, in which the variables have the following meanings:
A is —(CH 2 )p—R 1 , where R 1 is selected from the group consisting of pyrrolidine, morpholine, hexahydroazepine piperidine, —NR 5 R 6 and
wherein the cyclic amines are optionally substituted by one or two R 15 radicals, and R 15 is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl or phenyl, and R 5 , R 6 and R 7 are, independently of one another, selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, cyclohexyl, cyclopentyl, CH 2 Ph, Ph and CH 2 CH 2 Ph, wherein the phenyl rings are optionally substituted by R 6 , and
P is 1 or 2, and
B is phenyl, which is optionally substituted by up to two R 8 radicals, and A and B together can also be
and
R 16 is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl or (CH 2 ) 1-4 -phenyl, wherein the phenyl ring is optionally substituted by up to two R 6 radicals, and
D is selected from the group consisting of a bond, —(CH 2 ) 0-2 —O—(CH 2 ) 0-2 , —(CH 2 ) m —, —CH═CH—, and —C≡C—, and
R 2 is selected from the group consisting of chlorine, bromine, fluorine, C 1 -C 6 -alkyl, NHCO—C 1 -C 4 -alkyl, NHSO 2 —C 1 -C 4 -alkyl, NO 2 , —O—C 1 -C 4 -alkyl or NH 2 ,
R 3 is C 1 -C 6 -alkyl, branched or unbranched, and which may also carry a SCH 3 radical, a phenyl ring, imidazolyl ring, indolyl ring or a cyclopentyl, cycloheptyl or cyclohexyl ring which is in turn substituted by up to of two R 8 radicals, where R 8 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, branched or unbranched, —O—C 1 -C 4 -alkyl, OH, Cl, F, Br, I, CF 3 , NO 2 , NH 2 , ON, COOH, COO—C 1 -C 4 -alkyl, NHCO—C 1 -C 4 -alkyl, —NHSO 2 —C 1 -C 4 -alkyl and —SO 2 —C 1 -C 4 -alkyl; and
R 4 is selected from the group consisting of hydrogen, COOR 9 , CO—Z in which Z is NR 10 R 11
R 9 is hydrogen or C 1 -C 6 -alkyl, linear or branched, which may be substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and
R 10 is hydrogen or C 1 -C 6 -alkyl, linear or branched, which may be substituted by a phenyl ring which itself may also be substituted by one or two R 12 radicals,
R 11 is hydrogen or C 1 -C 6 alkyl, branched or unbranched, which may also be substituted by a phenyl ring which may also carry an R 9 radical, and
R 12 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, branched or unbranched, —O—C 1 -C 4 -alkyl, OH, Cl, F, Br, I, CF 3 , NO 2 , NH 2 , CN, COOH, COO—C 1 -C 4 -alkyl, —NHCO—C 1 -C 4 -alkyl, —NHCO-phenyl, —NHSO 2 —C 1 -C 4 -alkyl, NHSO 2 -phenyl, —SO 2 —C 1 -C 4 -alkyl or SO 2 -phenyl, and
R 13 is hydrogen or C 1 -C 6 -alkyl, linear or branched, which may be substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and
R 14 is hydrogen or C 1 -C 6 -alkyl, linear or branched, which may be substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and
n is a number 0, 1 or 2, and
m and q are, independently of one another, a number 0, 1, 2, 3 or 4.
2. An amide of the formula I as claimed in claim 1 where:
A is —CH 2 —R 1 ;
B is phenyl;
D is —CH═CH—;
R 2 is hydrogen;
R 3 is benzyl, CH 2 —CH 3 , CH 2 —CH 2 —CH 3 , CH 2 CH 2 CH 2 CH 3 , or CH 2 CH 2 CH 2 CH 2 CH 3 ;
R 4 is hydrogen and
all the remaining variables have the same meaning as in claim 1 .
3. An amide of the formula I as claimed in claim 1 , where:
A is —CH 2 —R 1 ;
B is phenyl;
D is —CH═CH—;
R 2 is hydrogen;
R 3 is benzyl, CH 2 —CH 3 , CH 2 —CH 2 —CH 3 , CH 2 CH 2 CH 2 CH 3 , or CH 2 CH 2 CH 2 CH 2 CH 3 ;
R 4 is CO—NH 2 and
all the remaining variables have the same meaning as in claim 1 .
4. A pharmaceutical preparation composition for oral, parenteral or intraperitonal use, comprising at least one amide of claim 1 per single dose, and conventional pharmaceutical ancillary substances.