13117-35-6Relevant academic research and scientific papers
Indole derivatives and its application on the medicament
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Paragraph 0381; 0391-0394, (2019/03/28)
The invention provides indole derivatives or stereisomers, tautomers, nitrogen oxides, solvate, metabolic products, pharmaceutically acceptable salts or prodrugs thereof for treating the alzheimer disease. The invention further discloses a pharmaceutical composition containing the compounds and a method of using the compounds or the pharmaceutical composition thereof to treat the alzheimer disease.
Binding of serotonin to the human serotonin transporter. Molecular modeling and experimental validation
Celik, Leyla,Sinning, Steffen,Severinsen, Kasper,Hansen, Carsten G.,Moller, Maria S.,Bols, Mikael,Wiborg, Ove,Schiott, Birgit
, p. 3853 - 3865 (2008/12/20)
Molecular modeling and structure-activity relationship studies were performed to propose a model for binding of the neurotransmitter serotonin (5-HT) to the human serotonin transporter (hSERT). Homology models were constructed using the crystal structure of a bacterial homologue, the leucine transporter from Aquifex aeolicus, as the template and three slightly different sequence alignments. Induced fit docking of 5-HT into hSERT homology models resulted in two different binding modes. Both show a salt bridge between Asp98 and the charged primary amine of 5-HT, and both have the 5-HT C6 position of the indole ring pointing toward Ala173. The difference between the two orientations of 5-HT is an enantiofacial discrimination of the indole ring, resulting in the 5-hydroxyl group of 5-HT being vicinal to either Ser438/Thr439 or Ala169/Ile172/Ala173. To assess the binding experimentally, binding affinities for 5-HT and 17 analogues toward wild type and 13 single point mutants of hSERT were measured using an approach termed paired mutant-ligand analogue complementation (PaMLAC). The proposed ligand-protein interaction was systematically examined by disrupting it through site-directed mutagenesis and reestablishing another interaction via a ligand analogue matching the mutated residue, thereby minimizing the risk of identifying indirect effects. The interactions between Asp98 and the primary amine of 5-HT and the interaction between the C6-position of 5-HT and hSERT position 173 was confirmed using PaMLAC. The measured binding affinities of various mutants and 5-HT analogues allowed for a distinction between the two proposed binding modes of 5-HT and biochemically support the model for 5-HT binding in hSERT where the 5-hydroxyl group is in close proximity to Thr439.
Homotryptamines as potent and selective serotonin reuptake inhibitors (SSRIs)
Schmitz, William D.,Denhart, Derek J.,Brenner, Allison B.,Ditta, Jonathan L.,Mattson, Ronald J.,Mattson, Gail K.,Molski, Thaddeus F.,Macor, John E.
, p. 1619 - 1621 (2007/10/03)
A series of N,N-dimethylhomotryptamines was prepared and their binding affinities at the serotonin transporter (SERT) were determined. Compounds possessing an electron withdrawing substituent at the C5-position of the indole nucleus were found to be poten
One-pot synthesis of homotryptamines from indoles
Denhart, Derek J.,Mattson, Ronald J.,Ditta, Jonathan L.,Macor, John E.
, p. 3803 - 3805 (2007/10/03)
A method is presented for the one-pot synthesis of homotryptamines by the MacMillan reaction of indoles with acrolein followed by reductive amination.
Design and synthesis of aminopropyl tetrahydroindole-based indolin-2-ones as selective and potent inhibitors of Src and Yes tyrosine kinase
Guan, Huiping,Laird, A. Douglas,Blake, Robert A.,Tang, Cho,Liang, Chris
, p. 187 - 190 (2007/10/03)
A novel series of substituted 3-[3-(aminopropyl)-4,5,6,7-tetrahydro-1H- indol-2-ylmethylene]-1,3-dihydro-indole-2-ones was discovered as potent inhibitors of the non-receptor tyrosine kinase Src and Yes. A structure-activity relationship was developed in order to optimize their potency and selectivity. Syntheses of these compounds are also described herein.
