62500-88-3Relevant academic research and scientific papers
Antioxydant activity of β-carboline derivatives in the LDL oxidation model
Hadjaz, Fariza,Besret, Soizic,Martin-Nizard, Fran?oise,Yous, Sa?d,Dilly, Sébastien,Lebegue, Nicolas,Chavatte, Philippe,Duriez, Patrick,Berthelot, Pascal,Carato, Pascal
, p. 2575 - 2585 (2011/06/23)
A series of β-carboline compounds were synthesized, starting from compound GWC22, their antioxidant activity was determined by inhibition of lipid peroxidation. The oxidation of LDL was induced in the presence of CuSO 4 or 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). The protective actions of these compounds against the cytotoxicity were evaluated with lactate dehydrogenase (LDH) activity in bovine aortic endothelial cells (BAECs) and cellular vitality by measuring mitochondrial activity in the presence of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Most of compounds showed an higher antioxidant activity than GWC22 derivative (R = 1.6 for 5 μM CuSO4). The best antioxidant activities are phenolic and benzyloxy derivatives with ratio R = 1.9 to 2.8 for 1 μM CuSO4. These substances have protective actions and increase significantly the cell viability.
The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5
Barsanti, Paul A.,Wang, Weibo,Ni, Zhi-Jie,Duhl, David,Brammeier, Nathan,Martin, Eric,Bussiere, Dirksen,Walter, Annette O.
scheme or table, p. 157 - 160 (2010/04/02)
A series of tetrahydro-β-carbolines were identified by HTS as inhibitors of the kinesin Eg5. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of removing potential metabolic liabilities and improving cellular potency.
N-methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT(1D) receptor agonist
Xu, Yao-Chang,Schaus, John M.,Walker, Clint,Krushinski, Joe,Adham, Nika,Zgombick, John M.,Liang, Sidney X.,Kohlman, Dan T.,Audia, James E.
, p. 526 - 531 (2007/10/03)
It has been observed that reported 5-HT(1D) receptor agonists have at least one heteroatom (N, O, or S) on the 5-substituent of the indole. This has led to the hypothesis that a 5-substituent capable of participating in hydrogen bonding is critical for conveying high affinity. This article describes the synthesis and biological evaluation of a new series of 5- alkyltryptamine analogues, which does not have a heteroatom in the 5- substituent group. In contrast to the hypothesis, 5-alkyltryptamines all exhibit high binding affinities for the human 5-HT(1D) receptor. The size of the lipophilic alkyl group at the 5-position of the indole has significant impact on the 5-HT(1D) binding affinity. Compounds with a tert-butyl group at the 5-position such as 9d, 10, and 11 were identified. These analogues display high binding affinity (K(i) 1 nM) and moderate receptor selectivity in comparison with known antimigraine agents such as sumatriptan, naratriptan, rizatriptan, and VML-251.
Binding of O-alkyl derivatives of serotonin at human 5-HT1Dβ receptors
Glennon, Richard A.,Hong, Seoung-Soo,Bondarev, Mikhail,Law, Ho,Dukat, Malgorzata,Rakhit, Suman,Power, Patricia,Fan, Ermei,Kinneau, Diana,Kamboj, Rajender,Teitler, Milt,Herrick-Davis, Katharine,Smith, Carol
, p. 314 - 322 (2007/10/03)
In humans, 5-HT1D serotonin receptors represent terminal autoreceptors, and there is some evidence that 5-HT1D ligands may be useful in the treatment of migraine. The most widely used 5-HT1D agonist is sumatriptan; however, this agent reportedly displays little selectivity for 5-HT1D versus 5-HT1A receptors. To identify novel serotonergic agents with enhanced 5-HT1D versus 5-HT1A selectivity, we attempted to take advantage of possible differences in the regions of bulk tolerance associated with the 5-position of the 5-HT binding sites for these two populations of receptors. Examination of a series of 5-(alkyloxy)tryptamine derivatives demonstrated that compounds with unbranched alkyl groups of up to eight carbon atoms bind with high affinity at human 5-HT1Dβ receptors (K(i) 300-fold). Branching of the alkyl chain, to 5-[(7,7-dimethylheptyl)oxy]tryptamine (15), results in an agent with somewhat lower affinity (5-HT1Dβ K(i) = 2.3 nM) but with greater (i.e., 400-fold) 5-HT1D versus 5-HT1A selectivity. Replacement of the oxygen atom of 10 with a methylene group (i.e., 20), replacement of the O-proximate methylene with a carbonyl group (i.e., ester 26), or cyclization of the aminoethyl moiety to a carbazole (e.g., 34, 36) or β- carboline (i.e., 37), result in reduced affinity and/or selectivity. None of the compounds examined displayed significant selectivity for 5-HT1Dβ versus 5-HT1Dα sites; nevertheless, compounds 10 (recently shown to behave as a 5- HT1D agonist) and 15 represent the most 5-HT1D versus 5-HT1A selective agents reported to date.
