Patent NZ-516918-A (NZ)
Title: Caspase inhibitors and uses thereof
Inventor: GOLEC JULIAN
IPC: A61K31/496
Filed: 2001-05-23
Abstract: A compound of formula I is described wherein: Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is H, CHN2, R, or CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, an aralkyl group, a heterocyclic group or a heterocyclylalkyl group; Y is an electronegative leaving group, R2 is CO2H, CH2CO2H or esters, amides or isosteres thereof; Ar is an optionally substituted aryl group; and R3 is H, an optionally substituted C1-6 alkyl, F2, CN, aryl or R3 is attached to Ar to form an unsaturated or partially saturated 5 or 6 membered fused ring having 0-2 heteroatoms; provided that if Ring A is unsubstituted piperidine; Ar is unsubstituted phenyl, R2 is CO2H or CO2-t-Bu; R3 is H then R1 is not -CH2-(5-(2,6-dichlorophenylmethyl)tetrazol-1-yl, and provided that R1 is not -(CH2)n-(Tet), wherein n is 1-4 and Tet is an optionally substituted tetrazole. The compounds can be used in the manufacturing of a medicament for treating a condition that is alleviated by treatment with a caspase inhibitor such as IL-1 mediated disease, an apoptosis mediated disease, an inflammatory disease, an autoimmune disease, a destructive bone disorder, a proliferative disorder, an infectious disease, a degenerative disease, a disease associated with cell death, an excess dietary alcohol intake disease, a viral mediated disease, uveitis, inflammatory peritonitis, osteoarthritis, pancreatitis, asthma, adult respiratory distress syndrome, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, chronic thyroiditis, Grave's disease, autoimmune gastritis, diabetes, autoimmune hemolytic anemia, autoimmune neutropenia, thrombocytopenia, chronic active hepatitis, myasthenia gravis, inflammatory bowel disease, Crohn's disease, psoriasis, atopic dermatitis, scarring, graft vs host disease, organ transplant rejection, osteoporosis, leukemias and related disorders, myelodysplastic syndrome, multiple myeloma-related bone disorder, acute myelogenous leukemia, chronic myelogenous leukemia, metastatic melanoma, Kapos's sarcoma, multiple myeloma, haemorrhagic shock, sepsis, septic shock, burns, Shigellosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, Kennedy's disease, prion disease, cerebral ischemia, epilepsy, myocardial ischemia, acute and chronic heart disease, myocardial infarction, congestive heart failure, atherosclerosis, coronary artery bypass graft, spinal muscular atrophy, amyotrophic lateral sclerosis, multiple sclerosis, HIV-related encephalitis, aging, alopecia, neurological damage due to stroke, ulcerative colitis, traumatic brain injury, spinal cord injury, hepatitis-B, hepatitis-C, hepatitis-G, yellow fever, dengue fever, or Japanese encephalitis, various forms of liver disease including alcoholic hepatitis, renal disease, polyaptic kidney disease, H. pylori-associated gastric and duodenal ulcer disease, HIV infection, tuberculosis, meningitis, complications associated with coronary artery bypass grafts, preservation of cells, preserving blood products and as a component of immunotherapy for the treatment of cancer.