| 摘要 |
The present invention provides substituted amino bicyclic-.beta.-lactam penam derivatives and substituted amino bicyclic-.beta.-lactam cepham derivatives and their diastereoisomers of general formula (I) as well as compositions containing such compounds, methods of making such compounds, and methods of using such compounds which exhibit excellent cysteine protease inhibitory activity and which may be used for treatment of different diseases such as cancer (including cancer metastasis), osteoporosis, rheumatoid arthritis, muscular dystrophy, myocardial infarction, pulmonary emphysema, septic shock, cerebral ischemia, decreased memory function, Alzheimer, cataract, malaria, glomerular basement membrane degradation, bacterial infection, inflammatory diseases, parasitic infections and viral infections. In said formula, R is a peptidyl residue of a single natural .alpha.-amino acid selected from a specific group of natural .alpha.-amino acids or a peptidyl residue of a single non-natural amino acid selected from a specified group of non-natural amino acids, in which natural or non-natural peptidyl residue the terminal NH2 group is unsubstituted or substituted once or twice with group R4; wherein R4 is selected from the group consisting of -COOR5, -COR5, -SO2R5, and -COR6; R5 is selected from the group consisting of (i) a C1-C6 alkyl group, (ii) a C2C6 alkenyl group, (iii) a C2-C6 alkenyl group, (iv) a C3-C6 cycloalkyl group, (v) a phenyl group, (vi) a naphthyl group, and (vii) a monocyclic or bicyclic heterocyclic group, which group (i), (ii), (iii), (iv), (v), (vi) or (vii) is unsubstituted or substituted; R6 is an amino group which is unsubstituted or substituted at least once with a C1-C6 alkyl group which is unsubstituted or substituted; R1 is selected from the group consisting of hydrogen, hydroxy, carboxy, -COOR5, -OR7-, -CONHR7, and C1-C6 alkyl, in which the C1-C6 alkyl is unsubstituted or substituted; wherein R7 is selected from the group consisting of: (i) C1-C6 alkyl which is unsubstituted or substituted, (ii) C2-C4 alkenyl which is unsubstitued or substituted, (iii) C2-C4 alkynyl, (iv) C3-C6 cycloalkyl, (v) phenyl which is unsubstituted or substituted, and (vi) a heterocycle which is monocyclic or bicyclic having 1, 2 or 3 heteroatoms selected from the group consisting of N, S, O; R2 and R3 are independently hydrogen or C1-C3 alkyl which is unsubstituted or substituted; n is 0, 1 or 2; and n1 is 0 or 1.
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