Patent NZ-520906-A (NZ)
Title: 2(alkyl)-, 5(4-pyrimidinyl)- substituted imidazole derivatives and pharmaceuticals thereof
Inventor: ADAMS JERRY LEROY
IPC: A61K31/506
Filed: 1999-05-20
Abstract: The compound of formula (I) is described wherein: X is oxygen, CH2, sulfur, or NH, or the moiety X-R1 is hydrogen; V is N; R1 is hydrogen, alkyl, aryl, aryl-alkyl, heterocyclic, heterocyclylc alkyl, heteroaryl, or heteroaryl-alkyl, wherein each of these moieties may be optionally substituted; X1 is hydrogen, XR1, optionally substituted alkyl, halogen, hydroxy, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylsulfinyl, CH2OR12, amino, mono and di- alkyl substituted amino, N(R10)C(O)Rb, N(RIO)S(O)2Rd, or an N-heterocyclyl ring which ring has from 5 to 7 members and optionally contains an additional heteroatom selected from oxygen, sulfur or NR15 ; Rb is hydrogen, alkyl, cycloalkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl heterocyclic or heterocyclyl alkyl; Rd is alkyl, cycloalkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclic or heterocyclyl alkyl; R2 is independently an optionally substituted alkyl, and wherein the two R2 moieties may together form a cycloalkyl or cycloalkenyl ring which ring may be optionally substituted; Y is alkenyl, hydroxy substituted alkyl, heterocyclic, or N (R10)C(Z)R3; R3 is alkyl, aryl, aryl-alkyl, heterocyclic, heterocyclyl alkyl, heteroaryl or heteroaryl-alkyl, wherein each of these moieties may be optionally substituted; Ar is an aryl or heteroaryl ring which ring may be optionally substituted. R10 is hydrogen or alkyl; R12 is hydrogen, C(Z)R13 or optionally substituted aryl, optionally substituted aryl-alkyl or S(O)2R25; Z is oxygen or sulfur; R13 is hydrogen, alkyl, cycloalkyl, heterocyclyl, heterocyclyl-alkyl, aryl, aryl-alkyl, heteroaryl or heteroaryl-alkyl wherein of these moieties may be optionally substituted; R15 is hydrogen, cyano, alkyl, cycloalkyl or aryl; R25 is alkyl, cycloalkyl, heterocyclyl, heterocyclyl-alkyl, aryl, aryl-alkyl, heteroaryl or heteroaryl-alkyl. The compound is used in the manufacture of a medicament for reducing inflammation associated with a rhinovirus infection or for treating a CSBP/RK/p38 kinase mediated disease. Preferably the disease is psoriatic arthritis, Reiter's syndrome, rheumatoid arthritis, gout, traumatic arthritis, rubella arthritis and acute synovitis, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic condition, sepsis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, Alzheimer's disease, stroke, neurotrauma, CNS injury, asthma, adult respiratory distress syndrome, cerebral malaria, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcososis, bone resorption disease, osteoporosis, restenosis, cardiac and renal reperfusion injury, chronic renal failure, congestive heart failure, angiogenic diseases, thrombosis, glomerularnephritis, diabetes, graft vs. host reaction, allograft rejection, inflammatory bowel disease, Crohn's disease, ulcerative colitis, multiple sclerosis, muscle degeneration, eczema, contact dermititis, psoriasis, sunburn, or conjunctivitis.