Imidazole Derivatives as New Potent and Selective 20‐HETE Synthase Inhibitors.

Abstract

Selective 20-HETE Synthase Inhibitors. -Synthesis and 20-HETE synthase inhibitor activity of a variety of N-arylimidazole derivatives are reported. Especially (IIIe) shows potent and selective inhibitory activity. -(NAKAMURA*, T.; KAKINUMA, H.; UMEMIYA, H.; AMADA, H.; MIYATA, N.; TANIGUCHI, K.; BANDO, K.; SATO*, M.; Bioorg. Med. Chem. Lett. 14 (2004) 2, 333-336; Med. Res. Lab.,

Synthesis, antimicrobial and antiviral evaluation of substituted imidazole derivatives

“…The appearance of medium bands at 3696.2 cm À1 in the IR spectra of compound 17 indicated the presence of a free OH in the carboxylic acid group of 2-substituted benzene. Further, the appearance of strong C]O stretching bands at 1695-1670 cm À1 in the IR spectra of (substituted phenyl)-[2-(substituted phenyl)-imidazol-1-yl]-methanones (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) demonstrated the presence of tertiary amide linkage between substituted benzoic acid and imidazole nucleus. Compounds 23 and 25 showed C-Br stretching at 522.8 cm À1 and 533.8 cm À1 , which confirms the presence of 2-bromo substituted benzene ring.…”

“…General procedure for the synthesis of (substituted phenyl)-[2-(substituted phenyl)-imidazol-1-yl]-methanones (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) A solution of 2-(substituted phenyl)-1H-imidazoles (1-12) (0.002 mol) in diethyl ether (50 ml) was added to a solution of corresponding substituted benzoyl chloride (0.002 mol) in diethyl ether (50 ml). The above mixture was stirred for 24 h at room temperature.…”

“…Therefore, coupling was carried out using sodium acetate along with stirring in cold conditions for the initial 3 h followed by 48 h stirring at room temperature which resulted in a solid product. For the synthesis of (substituted phenyl)-[2-(substituted phenyl)-imidazol-1-yl]-methanones (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), the key intermediates (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) were reacted with substituted benzoyl chloride which was prepared by the reaction of substituted benzoic acid with thionyl chloride. The physicochemical characteristics of the synthesized compounds are presented in Table 1.…”

“…Imidazole drugs have broadened scope in remedying various dispositions in clinical medicines. Medicinal properties include anticancer [11], b-lactamase inhibitors [12], 20-HETE synthase inhibitors [13], carboxypeptidase inhibitors [14], hemeoxygenase inhibitors [15], antiaging agents [16], anticoagulants [17], anti-inflammatory [18], antibacterial [19], antifungal [20], antiviral [21], antitubercular [22], antidiabetic [23] and antimalarial [24], all are unique characteristics known for imidazole derivatives.…”

Biological importance of imidazole nucleus in the new millennium

“…Therefore, the inhibition of 20-HETE is now considered as promising new target treatment of renal and cerebrovascular diseases. In continuation of their efforts in search of 20-HETE inhibitors, Nakamura et al (2004) synthesized imidazole-based compounds and found that [6-(4-imidazol-1-yl-phenoxy)-hexyl]dimethyl amine 25 exhibited strong inhibitory activity against 20-HETE synthase with an IC 50 value of 8.8 nM and more than 180-fold to over 15,000-fold selectivity toward CYP1A2, 2C9, 2C19, 2D6, and 3A4.…”