Substituted imidazoles having anti-cancer and cytokine inhibitory activity

A compound of the formula:

• wherein
• X is oxygen, carbon, sulfur, or nitrogen, or the moiety X—R1 is hydrogen;
• V is CH;
• R1 is hydrogen, C1-6alkyl, aryl, arylC1-6alkyl, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, pyrrolidine C1-6alkyl, piperidine C1-6alkyl, piperazine C1-6alkyl, morpholine C1-6alkyl, imidazolidine C1-6alkyl, pyrazolidine C1-6alkyl, pyrrole, quinoline, isoquinoline, pyridine, pyrimidine, oxazole, thiazole, thiadiazole, triazole, imidazole, or benzimidazole, pyrrole C1-6alkyl, quinoline C1-6alkyl, isoquinoline C1-6alkyl, pyridine C1-6alkyl, pyrimidine C1-6alkyl, oxazole C1-6alkyl, thiazole C1-6alkyl, thiadiazole C1-6alkyl, triazole C1-6alkyl, imidazole C1-6alkyl, or benzimidazole C1-6alkyl;
• wherein each of these moieties may be optionally substituted;
• X1 is hydrogen, XR1, optionally substituted C1-4 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 an additional heteroatom selected from oxygen, sulfur or NR15;
• Rb is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, pyrrolidine C1-4alkyl, piperidine C1-4alkyl, piperazine C1-4alkyl, morpholine C1-4alkyl, imidazolidine C1-4alkyl, pyrazolidine C1-4alkyl, pyrrole, quinoline, isoquinoline, pyridine, pyrimidine, oxazole, thiazole, thiadiazole, triazole, imidazole, or benzimidazole, pyrrole C1-4alkyl, quinoline C1-4alkyl, isoquinoline C1-4alkyl, pyridine C1-4alkyl, pyrimidine C1-4alkyl, oxazole C1-64alkyl, thiazole C1-4alkyl, thiadiazole C1-4alkyl, triazole C1-4alkyl, imidazole C1-4alkyl, or benzimidazole C1-4alkyl;
• Rd is C1-6 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, pyrrolidine C1-4alkyl, piperidine C1-4alkyl, piperazine C1-4alkyl, morpholine C1-4alkyl, imidazolidine C1-4alkyl, pyrazolidine C1-4alkyl, pyrrole, quinoline, isoquinoline, pyridine, pyrimidine, oxazole, thiazole, thiadiazole, triazole, imidazole, or benzimidazole, pyrrole C1-4alkyl, quinoline C1-4alkyl, isoquinoline C1-4alkyl, pyridine C1-4alkyl, pyrimidine C1-4alkyl, oxazole C1-64alkyl, thiazole C1-4alkyl, thiadiazole C1-4alkyl, triazole C1-4alkyl, imidazole C1-4alkyl, or benzimidazole C1-4alkyl;
• 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 ring may be optionally substituted;
• Y is a C2-4 alkenyl, hydroxy substituted C1-4 alkyl, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, or N(R10)C(Z)R3;
• R3 is C1-6alkyl, aryl, arylC1-6alkyl, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, pyrrolidine C1-6alkyl, piperidine C1-6alkyl, piperazine C1-6alkyl, morpholine C1-6alkyl, imidazolidine C1-6alkyl, pyrazolidine C1-6alkyl, pyrrole, quinoline, isoquinoline, pyridine, pyrimidine, oxazole, thiazole, thiadiazole, triazole, imidazole, or benzimidazole, pyrrole C1-6alkyl, quinoline C1-6alkyl, isoquinoline C1-6alkyl, pyridine C1-6alkyl, pyrimidine C1-6alkyl, oxazole C1-6alkyl, thiazole C1-6alkyl, thiadiazole C1-6alkyl, triazole C1-6alkyl, imidazole C1-6alkyl, or benzimidazole C1-6alkyl;
• wherein each of these moieties may be optionally substituted;
• Ar is an optionally substituted naphthyl;
• 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, aryl, arylC1-10 alkyl, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, pyrrolidine C1-10 alkyl, piperidine C1-10 alkyl, piperazine C1-10alkyl, morpholine C1-10alkyl, imidazolidine C1-10alkyl, pyrazolidine C1-10alkyl, pyrrole, quinoline, isoquinoline, pyridine, pyrimidine, oxazole, thiazole, thiadiazole, triazole, imidazole, or benzimidazole, pyrrole C1-10alkyl, quinoline C1-10alkyl, isoquinoline C1-10alkyl, pyridine C1-10alkyl, pyrimidine C1-10alkyl, oxazole C1-10alkyl, thiazole C1-10alkyl, thiadiazole C1-10alkyl, triazole C1-10alkyl, imidazole C1-10alkyl, or benzimidazole C1-10alkyl;
• 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, pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, pyrazolidine, pyrrolidine C1-10 alkyl, piperidine C1-10 alkyl, piperazine C1-10alkyl, morpholine C1-10alkyl, imidazolidine C1-10alkyl, pyrazolidine C1-10alkyl, pyrrole, quinoline, isoquinoline, pyridine, pyrimidine, oxazole, thiazole, thiadiazole, triazole, imidazole, or benzimidazole, pyrrole C1-10alkyl, quinoline C1-10alkyl, isoquinoline C1-10alkyl, pyridine C1-10alkyl, pyrimidine C1-10alkyl, oxazole C1-10alkyl, thiazole C1-10alkyl, thiadiazole C1-10alkyl, triazole C1-10alkyl, imidazole C1-10alkyl, or benzimidazole C1-10alkyl;
• or
• a pharmaceutically acceptable salt thereof.