99053-59-5Relevant academic research and scientific papers
Phenylglycine derivatives useful for treating disorders of the central nervous system
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, (2008/06/13)
A pharmaceutical compound of the formula: STR1 in which R1 is hydrogen, hydroxy or C1-6 alkoxy, R2 is hydrogen, carboxy, tetrazolyl, --SO2 H, --SO3 H, --OSO3 H, --CONHOH, or --P(OH)OR', --PO(OH)OR', --OP(OH)OR' or --OPO(OH)OR' where R' is hydrogen, C1-6 alkyl, C2-6 alkenyl or aryl C1-6 alkyl, R3 is hydrogen, hydroxy or C1-4 alkoxy, and R4 is fluoro, trifluoromethyl, nitro, C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, heteroaryl, optionally substituted aryl, optionally substituted aryl C1-6 alkyl, optionally substituted aryl C2-6 alkenyl, optionally substituted aryl C2-6 alkynyl, optionally substituted aryloxy, optionally substituted aryl C1-6 alkoxy, optionally substituted arylthio, optionally substituted aryl C1-6 alkylthio or --CONR"R'", --SO2 NR"R"", --NR"R'", --OCONR"R"' or --SONR"R'" where R" and R'" are each hydrogen, C1-6 alkyl or aryl C1-6 alkyl, or R" and R'" together form a C3-7 alkylene ring; provided that (i) R1, R2 and R3 are not all hydrogen,and (ii) when R2 and R3 are hydrogen and R1 is hydroxy, R4 is not fluoro; or a salt or ester thereof.
Mechanism and Products of Autoxidation of 5,7-Dihydroxytryptamine
Sinhababu, Achintya K.,Borchardt, Ronald T.
, p. 7618 - 7627 (2007/10/02)
The neurodegenerative effect of 5,7-dihydroxytryptamine (5,7-DHT) has been postulated to involve alkylation of neuronal proteins by its autooxidation product, which is believed to be corresponding p-quinone imine (5,7-DHTQ).To more precisely elucidate the mechanism of autoxidation of 5,7-DHT and its molecular mechanism of action in vivo, a series of methyl-substituted 5,7-DHT's, namely, 4-Me-, 6-Me-, and 4,6-Me2-5,7-DHT's (21a-c, respectively), were designed and synthesized as probes.The indole nucleus of these probes was constructed by the reductive cyclization of the corresponding 2,β-dinitrostyrene and the aminoethyl side chain was introduced via gramine methiodides.Cyclic voltammetric analysis of 5,7-DHT and 21a-c in 0.1 M H2SO4 and pH 4.0 and 7.4 buffers indicated that the primary product of electrochemical oxidation from each compound is the corresponding p-quinone imine which is very short lived ( 1 s).Like 5,7-DHT, 21a-c exhibited phenol-keto tautomerism but 21a and 21c did so to a much smaller extent as determined by UV and NMR spectroscopic methods.The predominant nonphenolic tautomeric form of 5,7-DHT, out of eight possible, was shown to be 27 (R1=R2=H).Polarographic measurements showed that, like 5,7-DHT, 21a-c react with O2 in a bimolecular fashion.Consideration of all the data indicates that the initial product of autoxidation in all cases is apparently a 4-hydroperoxy derivative.Only in the case of 5,7-DHT and 21b, the initially formed hydroperoxides break down to give colored products.These products were not stable enough to be isolated, but their UV-visible spectra correlate very well with similar known structures.The structure of this product in the case of 5,7-DHT is postulated to be the (4,7)p-quinone of 4,5,7-trihydroxytryptamine (4,5,7-THTQ, 35, R=H).The results of this study further indicate that in the autoxidation of 5,7-DHT, the p-quinone imine (5,7-DHTQ) is almost certainly not the primary product nor is it a transient intermediate in the formation of 4,5,7-THTQ. 4,5,7-THTQ also is unstable and appears to undergo further transformations at pH 7.4.
