Patent NZ-506963-A (NZ)
Title: Inhibitors of caspases
Inventor: MURCKO MARK A
IPC: A61P31/04
Filed: 1999-03-19
Abstract: A compound of formula I wherein: Y is formula (a) or (b), X is -C(R3)2- or -N(R3)-, m is 0 or 1 R1 is H, -C(O)R8, -C(O)C(O)R8, -S(0)2R8, -S(O)R8, -C(O)OR8, -C(O)N(H)R8, -S(0)2N(H)-R8, -S(O)N(H)-R8, -C(O)C(O)N(H)R8, - C(O)CH=CHR8, -C(O)CH2OR8, -C(O)CH2N(H)R8, -C(O)N(R8)2, - S(O)2N(R8)2, -S(O)N(R8)2, -C(O)C(O)N(R8)2, -C(O)CH2N(R8)2, - CH2R8, -CH2-alkenyl-R8, or -CH2-alkynyl-R8; R2 is-H, R3 are independently -H, an amino acid side chain,- R8, alkenyl-R9, or alkynyl-R9, or R2 and one R3 together with the atoms to which they are bound, form a 3 to 7 membered cyclic or heterocyclic ring system, wherein a hydrogen atom bound to any -alkyl or -cycloalkyl carbon atom is optionally replaced by-R10, a hydrogen atom bound to any -aryl or -heteroaryl carbon atom is optionally replaced by- R11, a hydrogen atom bound to any nitrogen atom of the ring system is optionally replaced by -R1; R4 and one R5 together with the atoms to which they are bound form a 3 to 7 membered cyclic or heterocyclic ring system, selected from formulas (i) to (xiii) and the other R5 is H, wherein a hydrogen atom bound to any nitrogen atom of the ring system is optionally replaced with R1; or R4 and one R5 together with the atoms to which they are bound form ring system of formula (xiv) and the other R5 is H R6 is-H; R7 is-OH,-OR8, or-N(H)OH; R8 is independently -alkyl, -cycloalkyl, -aryl, - heteroaryl, -heterocyclyl, -alkylcycloalkyl, -alkylaryl, - alkylheteroaryl, or -alkylheterocyclyl, wherein a hydrogen atom bound to any -alkyl, -cycloalkyl, aryl or -heteroaryl carbon atom or any nitrogen atom of the ring system can be optionally replaced as described above. R9 is independently-aryl,-heteroaryl, cycloalkyl, or- heterocyclyl, wherein a hydrogen atom bound to any -alkyl, - cycloalkyl, aryl or -heteroaryl carbon atom or any nitrogen atom of the ring system can be optionally replaced as described above; R10 is independently -OH, -SH, -F, -Cl, -Br, -I, -NO2, -CN, -NH2, -CO2H, -C(O)NH2, -N(H)C(O)H, -N(H)C(O)NH2, - perfluoroalkyl, -O-alkyl, -O-aryl, -O-alkylaryl, -N(H)alkyl, -N(H)aryl, -N(H)-alkylaryl, -N(alkyl)2, -C(O)N(H)alkyl, - C(O)N(alkyl)2, -N(H)C(O)alkyl, -N(H)C(O)N(H)alkyl, N(H)C(O)N(alkyl)2, -S-alkyl, -S-aryl, -S-alkylaryl, - S(O)2alkyl,-S(O)alkyl,-C(O)alkyl, -CH2NH2, -CH2N(H)alkyl, - CH2N(alkyl)2, -alkyl, -cycloalkyl, -aryl, -heteroaryl, - heterocyclyl, -alkylcycloalkyl, -alkylaryl, - alkylheteroaryl, or -alkylheterocyclyl, wherein a hydrogen atom bound to any-aryl, -heteroaryl or nitrogen atom is optionally replaced as described as above. R11 is independently -OH, -SH, -F, -Cl, -Br, -I, -NO2, -CN, -NH2,-CO2H, -C(O)NH2, -N(H)C(O)H, -N(H)C(O)NH2, -alkyl, - cycloalkyl, -perfluoroalkyl, -O-alkyl, -O-aryl, -O- alkylaryl, -N(H)alkyl, -N(H)aryl, -N(H)-alkylaryl, - N(alkyl)2, -C(O)N(H)alkyl, -C(O)N(alkyl)2, -N(H)C(O)alkyl, - N(H)C(O)N(H)alkyl, -N(H)C(O)N(alkyl)2, -S-alkyl, -S-aryl, -S- alkylaryl, -S(O)2alkyl, -CH2NH2, -C(O)alkyl, -CH2N(H)alkyl, or-CH2N(alkyl)2. Also described are pharmaceutical compositions comprising the compounds which can be used for treating rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, or multiple myeloma.