Patent NZ-526958-A (NZ)
Title: Novel 2-alkyl substituted imidazole compounds
Inventor: ADAMS JERRY LEROY
IPC: A61K31/4427
Filed: 1999-05-20
Abstract: A group of 2-position substituted imidazole compounds of formula (I), wherein: X is oxygen, CH2, sulfur, or NH, or the moiety X-R1 is hydrogen; V is CH; R1 is hydrogen, which may be optionally substituted with C1-6alkyl, aryl, arylC1-6alkyl, heterocyclic, heterocyclylC1-6 alkyl, heteroaryl, or heteroarylC 1-6alkyl; X1 is hydrogen, XR1, optionally substituted C 1-4 alkyl, halogen, hydroxy, optionally substituted C1-4 alkoxy, optionally substituted C1-4 alkylthio, optionally substituted C1-4 alkylsulfinyl,CH2OR12, amino, mono and di- C1-6 alkyl substituted amino, N(R10)C(O)Rb, N(R10)S(O)2Rd, or an N-heterocyclyl ring which ring has from 5 to 7 members and optionally contains oxygen, sulfur or NR15 as an additional heteroatom; Rb is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclyl, or heterocyclylC1-4 alkyl; Rd is C1-6 alkyl, C3-7cycloalkyl, aryl, arylC1-4alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclyl, or heterocyclylC1-4 alkyl; R2 is independently an optionally substituted C1-4 alkyl, and wherein the two R2 moieties may together form a C3-7 cycloalkyl or C5-7 cycloalkenyl ring which may be optionally substituted; Y is C(Z)OH; Ar is an aryl or heteroaryl ring which ring may be optionally substituted; R10 is hydrogen or C1-4 alkyl; R12 is hydrogen, C(Z) R13 or optionally substituted C1-4 alkyl, optionally substituted aryl, optionally substituted arylC1-4 alkyl, or S(O)2R25; Z is oxygen or sulfur ; R13 is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, heterocyclyl, heterocyclylC1-10 alkyl, aryl, arylC1-10 alkyl, heteroaryl or heteroaryl C1-10 alkyl, wherein all of these moieties may be optionally substituted; R15 is hydrogen, cyano, C1-4 alkyl, C3-7 cycloalkyl or aryl; R25 is C1-10 alkyl, C3-7 cycloalkyl, heterocyclyl, aryl, arylalkyl, heterocyclyl, heterocyclyl-C1-10alkyl, heteroaryl or heteroarylalkyl; or a pharmaceutically acceptable salt thereof. Methods for producing said compounds, and their use in treating CSBP/RK/p38 kinase mediated diseases is also described. CSBP/RK/p38 mediated diseases include 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. (62) Divided out of 508180