The present invention provides substituted amino bicyclic-.beta.-lactam penam derivatives and substituted amino bicyclic-.beta.-lactam cepham derivatives and their diastereoisomers of formula I, as well as compositions, methods of making, and methods of using, 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, ##STR1##whereinR 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 --NH.sub.2 group is unsubstituted or substituted once or twice with group R.sub.4,wherein R.sub.4 is selected from the group consisting of --COOR.sub.5, --COR.sub.5, --SO.sub.2 R.sub.5, and --COR.sub.6,R.sub.6 is an amino group which is unsubstituted or substituted at least once with a C.sub.1 -C.sub.6 alkyl group which is unsubstituted or substituted,R.sub.1 is selected from the group consisting of hydrogen, hydroxy, carboxy, --COOR.sub.6, --OR.sub.7, --CONHR.sub.7, and C.sub.1 -C.sub.5 alkyl, in which the C.sub.1 -C.sub.6 alkyl is unsubstituted or substituted,R.sub.2 and R.sub.3 are independently hydrogen or C.sub.1 -C.sub.3 alkyl which is unsubstituted or substituted,n is 0, 1, or 2, andn.sub.1 is 0 or 1.

Naeja Pharmaceutical Inc.

Substituted amino bicyclic-.beta.-lactam penam and cepham derivatives as cysteine protease inhibitors

Since sulfonamide derivatives of the present invention show strong inhibitory activity against cysteine protease such as calpain papain, cathepsin B, cathepsin H, cathepsin L, they can be used as remedies for muscular dystrophy, cataract, myocardial infarction, stroke, Alzheimer's disease, amyotrophia, osteoporosis, hypercalcemia or the like.

Mitsubishi Kasei Corporation

Sulfonamide derivatives

Aminoketone derivatives according to the present invention strongly inhibit thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L or the like and have excellent properties concerning absorbance on oral administration, tissue distribution and cell membrane permeability. The aminoketone derivatives cart thus be used as therapeutic agents for treating muscular dystrophy, cataract, cardiac infarction, stroke, Alzheimer's disease, amyotrophy, osteoporosis and hypercalcemia and so on. It may also be used as therapeutic agents for preventing metastasis of cancer. In addition, the present derivatives are also applicable as intermediates for the preparation of ketone derivatives, which have inhibitory activity against thiol protease.

Aminoketone derivatives

Alpha-aminoketone derivatives of the present invention strongly inhibit thiol protease such as papain, cathepsin B, cathepsin H, cathepsin L and calpain or the like and have excellent properties in absorbance on oral administration, tissue distribution and cell membrane permeability. The alpha-aminoketone derivatives can thus be used as therapeutic agents for treating muscular dystrophy, amyotrophy, cardiac infarction, stroke, Alzheimer's disease, disturbance of consciousness or dyskinesia caused upon brain trauma, multiple sclerosis, peripheral nervous neuropathy, cataract, inflammation, allergosis, fulminant hepatitis, osteoporosis, hypercalcemia, breast carcinoma, prostatic carcinoma or prostatomegaly. They may also be used as therapeutic agents for suppressing growth of cancer cells, preventing metastasis of cancer or suppressing aggregation of plaques.

cataract/protease

Substituted amino bicyclic-.beta.-lactam penam and cepham derivatives as cysteine protease inhibitors

Sulfonamide derivatives

Aminoketone derivatives

.alpha.-aminoketone derivatives

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