85079-45-4Relevant academic research and scientific papers
In vitro structure-activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety-depression model
Lewellyn, Kevin,Bialonska, Dobroslawa,Loria, Melissa J.,White, Stephen W.,Sufka, Kenneth J.,Zjawiony, Jordan K.
, p. 7083 - 7090 (2013/11/06)
Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms and have been shown to possess a range of biological activities. In vitro receptor binding assays showed that of the 12 serotonin receptor subtypes, analogues showed a high affinity for the 5-HT2B and 5-HT2C receptor subtypes, with selectivity for 5-HT2B over 5-HT2C. While no conclusions could be drawn about the number and position of N-methylations, bromination at C-4 and C-5 of the indole ring resulted in greater binding affinities, with Ki's as low as 35 nM. This data, combined with previous knowledge of the CNS activity of aplysinopsin analogs, suggested that these compounds may have potential as leads for antidepressant drugs. Compounds 3c, 3u, and 3x were evaluated in the chick anxiety-depression model to assess their in vivo efficacy. Compound 3c showed a modest antidepressant effect at a dose of 30 nM/kg in the animal model.
Synthesis and structure-affinity relationships of novel small molecule natural product derivatives capable of discriminating between serotonin 5-HT1A, 5-HT2A, 5-HT2C receptor subtypes
Cummings, David F.,Canseco, Diana C.,Sheth, Pratikkumar,Johnson, James E.,Schetz, John A.
experimental part, p. 4783 - 4792 (2010/08/06)
Efforts to develop ligands that distinguish between clinically relevant 5-HT2A and 5-HT2C serotonin receptor subtypes have been challenging, because their sequences have high homology. Previous studies reported that a novel aplysinopsin belonging to a chemical class of natural products isolated from a marine sponge was selective for the 5-HT2C over the 5-HT2A receptor subtype. Our goal was to explore the 5-HT2A/2C receptor structure-affinity relationships of derivatives based on the aplysinopsin natural product pharmacophore. Twenty aplysinopsin derivatives were synthesized, purified and tested for their affinities for cloned human serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptor subtypes. Four compounds in this series had >30-fold selectivity for 5-HT2A or 5-HT2C receptors. The compound (E)-5-((5,6-dichloro-1H-indol-3-yl)methylene)- 2-imino-1,3-dimethylimidazolidin-4-one (UNT-TWU-22, 16) had approximately 2100-fold selectivity for the serotonin 5-HT2C receptor subtype: an affinity for 5-HT2C equal to 46 nM and no detectable affinity for the 5-HT1A or 5-HT2A receptor subtypes. The two most important factors controlling 5-HT2A or 5-HT2C receptor subtype selectivity were the combined R1,R3-alkylation of the imidazolidinone ring and the type and number of halogens on the indole ring of the aplysinopsin pharmacophore.
Synthesis and characterization of aplysinopsin analogs
Johnson, James E.,Canseco, Diana C.,Dolliver, Debra D.,Schetz, John A.,Fronczek, Frank R.
experimental part, p. 329 - 336 (2011/09/21)
Three aplysinopsin analogs were synthesized by reacting 5-bromo-5-fluoro- and 6-bromoindole-3-carboxaldehyde with either creatinine or 2-imino-1,3-dimethyl-imidazolidin-4-one or 2-imino-1-methyl-3-ethylimidazolidin- 4-one Single crystal structures on 5-bromo-4′-de-N-methylaplysinopsin DMF solvate [from creatinine, space group P21/n, lattice parameters a = 13.117(3) A, b = 8.6663(15) A, c = 14.743(3) A, β = 99.538(10)° at 173 K], 5-fluoroaplysinopsin DMF solvate [from 2-imino1,3-dimethyl-imidazolidin-4-one, space group P21/c, lattice parameters a = 11.114(3) A, b = 19.118(2) A, c = 8.503(2) A, β = 112.290(7)°], and 6-bromoindole-3-carboxaldehyde (space group P21/n, lattice parameters a = 7.657(2) A, b = 7.933(2) A, c = 13.521(3) A, β = 99.046(13)°) have been determined. Characterizations include spectrometric identifications employing IR, UV, HRMS, and 1H and 13C NMR. 5-Bromo-4′-de-N- methylaplysinopsin and 5-fluoroapIysinopsin exist in the E configuration. Springer Science+Business Media, LLC 2008.
A new synthesis of 5-bromoaplysinopsin, 6-bromoaplysinopsin and 3'-demethylaplysinopsin and their biological activities
Gulati, Deepa,Chauhan, P. M. S.,Pratap, Ram,Bhakuni, D. S.
, p. 10 - 16 (2007/10/02)
A new synthesis of 5-bromoaplysinopsin (11), 6-bromoaplysinopsin (15) and 3'-demethylaplysinopsin (24) has been developed.A number of their analogues have been synthesized and evaluated for biological activities.Of the compounds tested, compounds 5, 7-9 a
