Patent NZ-528282-A (NZ)
Title: Interleukin-1 beta converting enzyme inhibitors
Inventor: WANNAMAKER MARION W
IPC: A61P31/04
Filed: 1999-03-19
Abstract: Compounds of formula I are described wherein; Y is formula (a) or (b); X is -C(R3)2- or -N (R3)- ; m is 0 or 1 R1 is -C(O)C(O)R8, -S(O)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, -S(O)N(R8)2, -C(O)C(O)N(R8)2, -C(O)CH2N(R8)2, -CH2-alkenyl-R8, or -CH2-alkynyl-R8; R2 is-H and each R3 is independently -H, an amino acid side chain, -R8, alkenyl-R9, or alkynyl-R9, or each R3 together with the atom to which they are bound forma 3 to 7 membered cyclic or heterocyclic ring system, 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, -cycloalkyl, aryl or -heteroaryl carbon atom or any nitrogen atom of the ring system can be optionally replaced; R4 is H and each R5 is -H an amino acid side chain, -R8, -alkenyl-R9 or alkenyl-R9 or R4 and one of 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 (ix) 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; 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; 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; 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; 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. The compounds can be used in medicament for inhibiting ICE-mediated function and decreasing IGIF or IFN-gamma production and for treating disorders such as 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. (62) Divided out of 506963