DERIVADOS DE 1,2-DIAZEPAN COMO INHIBIDORES DE LA ENZIMA CONVERTIDORA DE INTERLEUQUINA-1 BETA

• Main Authors: CHARIFSON, PAUL, MULLICAN, MICHAEL, D, WANNAMAKER, MARION, W, LAUFFER, DAVID, J
• Format: Patent
• Language: Spanish
• Published: 01.12.2005
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Un compuesto representado por la **fórmula** en la que m es 0 ó 1; W es -CH2-, -C(O)-, S(O)2 o -S(O)-; X es -C(H)-, -C(R8)-, o Z es-CH2-, -O-, -S-, o -N(R1)-, con tal de que si Z es - N(R1)-, entonces W es -C(O)-, -S(O)2- o -S(O)-; cada R1 es, por separado, -H, -S(O)2-CH3, R2 es -C(O)R8, -C(O)C(O)R8, -S(O)2R8, -S(O)R8, -C(O)OR8, - C(O)N(H)R8, -S(O)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, -CH2-R8, -CH2-alquenil-R8 o -CH2-alquinil-R8; R8 es -H, una cadena lateral de aminoácido, cada R4 es independientemente -OH, -F, -CI, -Br, -I, -NO2, -CN, -NH2, -CO2H, -C(O)NH2, -N(H)C(O)H, -N(H)C(O)NH2, - alquilo, -cicloalquilo, -perfluoroalquilo, -O-alquilo, - N(H)alquilo, -N(alquilo)2, -C(O)N(H)alquilo, - C(O)N(alquilo)2, -N(H)C(O)alquilo, -N(H)C(O)N(H)alquilo, - N(H)C(O)N(alquilo)2, -S-alquilo, -S(O)2alquilo, - S(O)alquilo, -C(O)alquilo, -CH2NH2, -CH2N(H)alquilo, - CH2N(alquilo)2 o-N(H)C(O)Oalquilo; R5 es -OH, -OR8, -N(H)OH o -N(H)SO2R8; R6 es -H, -CH2OR9, -CH2SR10, -CH2N(H)R9, -CH2N(R9)R11, - C(H)N2, -CH2F, -CH2CI, -CH2Br, -CH2I, -C(O)N(R11)2, -R13 o -R14. The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1beta converting enzyme ("ICE") inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1-("IL-1"), apoptosis-, interferon-gamma inducing factor-(IGIF), or interferon-gamma-("IFN-gamma") mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN-gamma production and methods for treating interleukin-1, apoptosis-, and interferon-gamma-mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.