Synthesis of 1-(4-hydroxy-3-methoxyphenyl)-2,3,4,9-tetrahydro-1H- β-carboline-3-carboxylic acid derivatives as mast cell stabilizers

AbstractThe role of mast cells can be protective or harmful; depending upon the physiological/pathological condition in which they get activated. The latter role is due to mast cell degranulation and release of an array of incendiary mediators. Mast cells have a well-established role in diseases like allergy, eczema, anaphylactic shock, mastocytosis, and other miscellaneous mast cell diseases. Previously, we have shown that spiro- β-carboline alkylated analogs have mast cells stabilization activity. Recently, tryptophan has been reported to suppress the mast cell activation. Indeed, vanillin analogs were reported to inhibit degranulation. Hence, it is worthwhile to synthesize 21 constrained analogs of tryptophan with vanilli n which are derivatives of 2,3,4,9-tetrahydro-β-carboline-3-carboxylic acid and their evaluation forex-vivo inhibition of the compound 48/80 induced mast degranulation activity. By comparing IC50 ( µM) values with standard drug cromolyn sodium (IC50 = 0.486 ± 0.003 µM), the bulky group compounds like tri-substituted isopropyl (compound 7;cis-1-(4-Isopropoxy-3-methoxyphenyl)-2,9-diisopropyl-2,3,4,9-tetrahydro-1H- β-carboline-3-carboxylic acid; IC50 = 0.389 ± 0.015 µM) and tri-substituted octyl (compound 17;cis-1-(3 ’-Methoxy-4’-(octyloxy)phenyl)-2,9-dioctyl-2,3,4,9-tetrahydro-1H- β-carboline-3-carboxylic acid; IC50 = 0.237 ± 0.031 µM) were found to be equipotent. Furthermore, the polar group SO2 containing compo...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research