Thiazole derivatives
AssigneeHoffman-La Roche Inc.
InventorsLeo Alig, Albrecht Edenhofer, Kurt Hilpert, Thomas Weller
Life of this patent
Estimating the term…
Abstract
Compounds of the formula: as well as pharmaceutically usable salts and esters thereof, wherein R1, R2 and R3 have the significance ascribed herein, inhibit binding of adhesive proteins to the surface of different types of cell and accordingly influence cell-cell and cell-matrix interactions. These compounds can be used in the form of pharmaceutical preparations for the control or prevention of neoplasms, tumor metastasing, tumor growth, osteoporosis, Paget's disease, diabetic retinopathy, macular degeneration, restenosis following vascular intervention, psoriasis, arthritis, fibrosis, kidney failure, as well as infection caused by viruses, bacteria or fungi.
Claims90
A compound having the formula:
- R3 is hydrogen, alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, carboxy, alkyl-O—CO—, or aralkyl-O—CO—;
- R4 is hydrogen, alkyl, cycloalkyl, aryl, or heteroaryl;
- R5 and R6 are each independently hydrogen, alkyl, cycloalkyl, or heteroaryl;
- R9 is hydrogen, alkyl, or cycloalkyl;
- R10 is aryl, aralkyl, heterocyclyl, heterocyclylalkyl, hydroxy, hydrogen, or alkyl, or R10 is carboxy, carboxyalkyl, alkyl-O—CO—, aralkyl-O—CO—, alkyl-CO—, aralkyl-CO—, heteroarylalkyl-CO—, alkylsulphonyl, arylsulphonyl or heteroarylsulphonyl and k is zero, or R10 is an α-amino acid bonded via the amino group and l is zero and k is 1;
- A is carbonyl or sulphonyl;
- B is hydrogen, alkyl, or cycloalkyl;
- a is an integer from 0 to 2 but not being zero when R1 is —NH2;
- b is an integer from 0 to 4;
- c, d, f, g, k, l and m are each independently an integer from 0 to 1, whereby c, f and g are not simultaneously 0 and whereby m is not 0 when f or g is 1;
- i is an integer from 0 to 1, whereby k and l are also 0 when i is 0;
- e is an integer from 0 to 3;
- h is an integer from 0 to 5;
- j is an integer from 0 to 2;
- and the sum of e, h and j is an integer from 2 to 7;
- and the pharmaceutically usable salts and esters thereof.
A process for manufacturing a compound of the formula:
- R3 is hydrogen, alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, carboxy, alkyl-O—CO—, or aralkyl-O—CO—;
- R4 is hydrogen, alkyl, cycloalkyl, aryl, or heteroaryl;
- R5 and R6 are each independently hydrogen, alkyl, cycloalkyl, or heteroaryl;
- R9 is hydrogen, alkyl, or cycloalkyl;
- R10 is aryl, aralkyl, heterocyclyl, heterocyclylalkyl, hydroxy, hydrogen, or alkyl, or R10 is carboxy, carboxyalkyl, alkyl-O—CO—, aralkyl-O—CO—, alkyl-CO—, aralkyl-CO—, heteroarylalkyl-CO—, alkylsulphonyl, arylsulphonyl or heteroarylsulphonyl and k is zero, or R10 is an α-amino acid bonded via the amino group and l is zero and k is 1;
- A is carbonyl or sulphonyl;
- B is hydrogen, alkyl, or cycloalkyl;
- a is an integer from 0 to 2 but not being zero when R1 is —NH2;
- b is an integer from 0 to 4;
- c, d, f, g, k, l and m are each independently an integer from 0 to 1, whereby c, f and g are not simultaneously 0 and whereby m is not 0 when f or g is 1;
- i is an integer from 0 to 1, whereby k and l are also 0 when i is 0;
- e is an integer from 0 to 3;
- h is an integer from 0 to 5;
- j is an integer from 0 to 2;
- and the sum of e, h and j is an integer from 2 to 7;
- and the pharmaceutically usable salts and esters thereof;
- which process comprises reacting a compound of the formula:
- with an amine of the formula:
- wherein R1, R3, R9, R10, A, B and d to m are as above, c is equal to 1 and R03 is alkyl or aralkyl.
Dependencies are inferred from the claim text.