Kolasa, Teodozyj published the artcileSymmetrical Bis(heteroarylmethoxyphenyl)alkylcarboxylic Acids as Inhibitors of Leukotriene Biosynthesis, SDS of cas: 4760-35-4, the publication is Journal of Medicinal Chemistry (2000), 43(17), 3322-3334, database is CAplus and MEDLINE.
Sym. bis(quinolylmethoxyphenyl)alkylcarboxylic acids were investigated as inhibitors of leukotriene biosynthesis and the sodium salt of bisquinolylmethoxyphenylpentanoic acid I met our design parameters for a drug candidate (ABT-080). I was readily synthesized in three steps from com. available diphenolic acid. Against intact human neutrophils, the sodium salt of I inhibited ionophore-stimulated LTB4 formation with an IC50 = 20 nM. In zymosan-stimulated mouse peritoneal macrophages producing both LTC4 and PGE2, the sodium salt of I showed 9000-fold selectivity for inhibition of LTC4 (IC50 = 0.16 nM) over PGE2 (IC50 = 1500 nM). Preliminary pharmacokinetic evaluation in rat and cynomolgus monkey demonstrated good oral bioavailability and elimination half-lives of 9 and 5 h, resp. Pharmacol. evaluation of leukotriene inhibition with oral dosing was demonstrated in a rat pleural inflammation model (ED50 = 3 mg/kg) and a rat peritoneal passive anaphylaxis model (LTB4, ED50 = 2.5 mg/kg; LTE4, ED50 = 1.0 mg/kg). In a model of airway constriction induced by antigen challenge in actively sensitized guinea pigs, the sodium salt of I dosed orally blocked bronchoconstriction with an ED50 = 0.4 mg/kg, the most potent activity we have observed for any leukotriene inhibitor in this model. The mode of inhibitory action of the sodium salt of I occurs at the stage of 5-lipoxygenase biosynthesis as it blocks both leukotriene pathways leading to LTB4 and LTC4 but not PGH2 biosynthesis. However,the sodium salt of I does not inhibit 5-lipoxygenase catalysis in a broken cell enzyme assay; therefore the sodium salt of I likely acts as a FLAP inhibitor.
Journal of Medicinal Chemistry published new progress about 4760-35-4. 4760-35-4 belongs to imidazoles-derivatives, auxiliary class Chloride,Benzimidazole, name is 2-(Chloromethyl)-1-methyl-1H-benzo[d]imidazole, and the molecular formula is C9H9ClN2, SDS of cas: 4760-35-4.
Referemce:
https://en.wikipedia.org/wiki/Imidazole,
Imidazole | C3H4N2 – PubChem