Adhesion receptor antagonists
AssigneeMerck Patent Gesellschaft mit beschraenkter Haftung
InventorsJoachim Gante, Hörst Juraszyk, Peter Raddatz, Hanns Wurziger, Sabine Bernotat-Danielowski, Guido Melzer
Life of this patent
Estimating the term…
Abstract
Compounds of the formula I in which R1, R2 and R3 have the stated meanings, and their physiologically acceptable salts, inhibit the binding of fibrinogen to the corresponding receptor and can be used for the treatment of thromboses, osteoporoses, oncoses, stroke, myocardial infarct, ischemias, inflammations, arteriosclerosis and osteolytic disorders.
Claims17
A compound of the formula I
- in which
- with
- B=CH2, CO or CS, R10=OH or H and
- m=0, 1, 2, 3 or 4;
- or
- with
- B=CH2, CO or CS, U=CH2 or CO and
- R9=H, CO2H or CO2A, and q=0, 1, 2 or 3;
- R1 is H, A, Ar—CO, A—CO, OH, OA or AO—CO;
- R2 is OH, OA, OAr, OHet, NHOH, NH2, NHA or NA2;
- R3 is A—CO, Ar—CO, Het—CO, Het—O—CO, Ar—O—CO, A—O—CO, Ar—SO2 or A—SO2;
- A is alkyl with 1 to 6 C atoms;
- Ar is aryl of 6 to 10 C atoms, or diphenylmethyl or benzyl which are unsubstituted or substituted once, twice or three times by A, F, Cl, Br, I, OA, —O—CH2—O—, COOA, COOH, CF3, OH, NO2, CN, NH2, O—CO—A, NHA or NA2;
- and
- Het is a mono- or binuclear saturated, unsaturated or aromatic heterocycle with 1 to 4 N, O and/or S atoms, which can be unsubstituted or substituted once by F, Cl, Br, CF3, A, OH, OA, CN or NO2,
- and their physiologically acceptable salts and solvates.
A compound which is:
- (a) 3-p-(N-benzoylamidino)phenyl-5-[4-(ethoxycarbonylmethyl)piperazinomethyl]-2-oxazolidinone;
- or
- (b) 3-p-(3-pyridylcarbonylamidino)phenyl-5-[4-(ethoxycarbonylmethyl)piperazinomethyl]-2-oxazolidinone;
- (c) 3-p-(N-methyl-4-piperidyloxycarbonyl-amidino)phenyl-5-[4-(ethoxycarbonylmethyl)-piperazinomethyl]-2-oxazolidinone;
- (d) 3-p-(N-methylsulfonylamidino)phenyl-5-[4-(carboxyethylpiperazinomethyl]-2-oxazolidinone;
- (e) 3-p-(N-1-naphthoylamidino)phenyl-5-[4-(carboxyethylpiperazinomethyl]-2-oxazolidinone;
- (f) 3-p-[N-(ethoxycarbonylmethylcarbamoyl)-amidino]phenyl-5-[4-(tert-butoxycarbonyl-ethyl)piperazinomethyl]-2-oxazolidinone;
- (g) 3-p-[N-methylsulfonylamidino]phenyl-5-[4-(tert-butoxycarbonylethyl)piperazinomethyl]-2-oxazolidinone.
A method for the treatment of thromboses, stroke, myocardial infarct, angina pectoris, osteoporosis, restenosis after angioplasty, ischemias, inflammations, arteriosclerosis, acute kidney failure or tumors by prevention of tumor metastasis which comprises administering a treatment effective amount of a compound of the formula I
- in which
- R is
- with
- B=CH2, CO or CS, R10=OH or H and
- m=0, 1, 2, 3 or 4;
- or
- with
- B=CH2, CO or CS, U=CH2 or CO and
- R9=H, CO2H or CO2A, and q=0, 1, 2 or 3;
- R1 is H, A, Ar—CO, A—CO, OH, OA or AO—CO;
- R2 is OH, OA, OAr, OHet, NHOH, NH2 NHA or NA2;
- R3 is A—CO, Ar—CO, Het—CO, Het—O—CO, Ar—O—CO, A—O—CO, Ar—SO2 or A—SO2;
- A is alkyl with 1 to 6 C atoms;
- Ar is aryl of 6 to 10 C atoms, or diphenylmethyl or benzyl which are unsubstituted or substituted once, twice or three times by A, F, Cl, Br, I, OA, —O—CH2—O, COOA, COOH, CF3, OH, NO2, CN, NH2, O—CO—A, NHA or NH2;
- and
- Het is a mono- or binuclear saturated, unsaturated or aromatic heterocycle with 1 to 4 N, O and/or S atoms, which can be unsubstituted or substituted once by F, Cl, Br, CF3, A, OH, OA, CN or NO2,
- or one of its physiologically acceptable salts or solvates.
Dependencies are inferred from the claim text.