150871-44-6Relevant articles and documents
Neuroprotective or neurotoxic activity of 1-methyl-1,2,3,4- tetrahydroisoquinoline and related compounds
Okuda, Katsuhiro,Kotake, Yaichiro,Ohta, Shigeru
, p. 2853 - 2855 (2003)
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) 1 and various 5- or 6,7-substituted analogues were synthesized and assayed for neurotoxicity towards SH-SY5Y cells. Among mono-substituted derivatives of 1, hydroxyl substitution decreased the toxicity, while methoxyl substitution increased it. Disubstituted derivatives of 1, 5a and 5b, showed the opposite tendency. Hydroxy-1MeTIQ derivatives were tested for neuroprotective activity, and 3b and 4b exhibited greater efficacy than 1. We suggest that hydroxy-1MeTIQ derivatives, especially 4b, may have potential for the treatment of Parkinson's disease.
Design and Synthesis of New Naphthalenic Derivatives as Ligands for 2-Iodomelatonin Binding Sites
Langlois, Michel,Bremont, Beatrice,Shen, Shuren,Poncet, Annie,Andrieux, Jean,et al.
, p. 2050 - 2060 (2007/10/02)
New melatonin-like agents were designed from the frameworks of 2,5-dimethoxyphenethylamine, an important structural moiety for the 5-HT receptor, and (2-methoxynaphthyl)ethylamine.The compounds were synthesized by classical methods and evaluated in binding assays with chicken brain membranes using 2-(125I>iodomelatonin as the radioligand.Preliminary studies on the series of N-acyl-disubstituted phenethylamines showed the favorable role of the methoxy group in the ortho position of the side chain on the affinity for the receptor ( Ki = 8 +/- 0.2 nM ) for N-propionamide (3o).This effect was confirmed in a series of the naphthalene derivatives, a bioisosteric moiety of the indole ring, and several potent ligands for melatonin binding sites were prepared such as N-propionamide (4b) ( Ki = 0.67 +/- 0.05 nM ) and N-cyclopropylformamide (Ki = 0.05 +/- 0.004 nM ( (4k).Structure-activity relationships are discussed with regard to melatonin and bioisosteric naphthalenic compound 2.The Ki value for 4b was affected to a similar extent to that of melatonin by GTP-γ-S or Mn2+ in competition experiments, suggesting an agonist profile for this compound.
