36765-74-9Relevant academic research and scientific papers
Synthesis, structure-affinity relationships, and modeling of AMDA analogs at 5-HT2A and H1 receptors: Structural factors contributing to selectivity
Shah, Jitesh R.,Mosier, Philip D.,Roth, Bryan L.,Kellogg, Glen E.,Westkaemper, Richard B.
, p. 6496 - 6504 (2009)
Histamine H1 and serotonin 5-HT2A receptors present in the CNS have been implicated in various neuropsychiatric disorders. 9-Aminomethyl-9,10-dihydroanthracene (AMDA), a conformationally constrained diarylalkyl amine derivative, has affinity for both of these receptors. A structure-affinity relationship (SAFIR) study was carried out studying the effects of N-methylation, varying the linker chain length and constraint of the aromatic rings on the binding affinities of the compounds with the 5-HT2A and H1 receptors. Homology modeling of the 5-HT2A and H1 receptors suggests that AMDA and its analogs, the parent of which is a 5-HT2A antagonist, can bind in a fashion analogous to that of classical H1 antagonists whose ring systems are oriented toward the fifth and sixth transmembrane helices. The modeled orientation of the ligands are consistent with the reported site-directed mutagenesis data for 5-HT2A and H1 receptors and provide a potential explanation for the selectivity of ligands acting at both receptors.
Heterocyclization involving benzylic C(sp3)-H functionalization enabled by visible light photoredox catalysis
Pandey, Ganesh,Laha, Ramkrishna,Mondal, Pradip Kumar
supporting information, p. 9689 - 9692 (2019/08/15)
A general and efficient method for heterocyclization involving benzylic C(sp3)-H functionalization enabled by visible light photoredox catalysis to access a wide range of structurally diverse oxygen as well as nitrogen heterocycles up to a gram scale is reported. The potential application of this new methodology is demonstrated by the total synthesis of (-)-codonopsinine and (+)-centrolobine. Herein it is proposed that selectfluor, unlike a fluorinating reagent, acts as an oxidative quencher and a hydrogen radical acceptor.
An Iodine-Catalyzed Hofmann-L?ffler Reaction
Martínez, Claudio,Mu?iz, Kilian
supporting information, p. 8287 - 8291 (2015/07/07)
Iodine reagents have been identified as economically and ecologically benign alternatives to transition metals, although their application as molecular catalysts in challenging C-H oxidation reactions has remained elusive. An attractive iodine oxidation catalysis is now shown to promote the convenient conversion of carbon-hydrogen bonds into carbon-nitrogen bonds with unprecedented complete selectivity. The reaction proceeds by two interlocked catalytic cycles comprising a radical chain reaction, which is initiated by visible light as energy source. This unorthodox synthetic strategy for the direct oxidative amination of alkyl groups has no biosynthetic precedence and provides an efficient and straightforward access to a general class of saturated nitrogenated heterocycles.
2-Substituted 4-hydroxybutanamides as potential inhibitors of γ-aminobutyric acid transporters mGAT1-mGAT4: Synthesis and biological evaluation
Kowalczyk, Paula,Sa?at, Kinga,H?fner, Georg C.,Guzior, Natalia,Filipek, Barbara,Wanner, Klaus T.,Kulig, Katarzyna
, p. 5154 - 5167 (2013/09/02)
A series of 2-substituted 4-hydroxybutanamide derivatives has been synthesized by the aminolysis of appropriate 2-substituted dihydrofuran-2(3H)- one derivatives with various substituted benzylamines. The final compounds have been evaluated for their capability of inhibiting the GABA transport proteins GAT1-4 stably expressed in HEK-239 cell lines. The pIC50 values determined were in the range 4.21-5.14. Two compounds (16a and 16d), which displayed the most interesting profiles in in vitro tests, have also been subjected to further preliminary behavioral studies, evaluating their antinociceptive activity in hot-plate, writhing, and formalin tests. Their influence on motor coordination has also been assessed.
Aminomethyltetrazoles as potential inhibitors of the c-aminobutyric acid transporters mGAT1-mGAT4: Synthesis and biological evaluation
Schaffert, Eva S.,H?fner, Georg,Wanner, Klaus T.
supporting information; experimental part, p. 6492 - 6504 (2011/12/14)
1,5-Disubstituted and 5-monosubstituted aminomethyltetrazole derivatives derived from glycine were synthesized employing a TMSN3-modified variant of the Ugi reaction as a key step. All compounds were evaluated regarding their inhibitory potency and subtype selectivity at the four murine GABA transporter subtypes mGAT1-mGAT4. Though none of the 5-monosubstituted tetrazoles turned out to inhibit [3H]GABA uptake to a significant extent, the 1,5-disubstituted tetrazole derivatives displayed a distinct activity, especially at the GABA transport proteins mGAT2-mGAT4. Thus, a reasonable potent and selective inhibitor of mGAT3 was found. Additionally, two more compounds were identified as potent inhibitors of mGAT2. This is especially relevant, as up to date only few potent inhibitors of mGAT2 that do not affect mGAT1 are known.
AZACYCLIC COMPOUNDS AS INHIBITORS OF SENSORY NEURONE SPECIFIC CHANNELS
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Page 50, (2010/02/10)
Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents wherein: X is -N- or -CH-; n is from 0 to 3.
Selective inhibitors of GABA uptake: Synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues
Clausen, Rasmus P.,Moltzen, Ejner K.,Perregaard, Jens,Lenz, Sibylle M.,Sanchez, Connie,Falch, Erik,Fr?lund, Bente,Bolvig, Tina,Sarup, Alan,Larsson, Orla M.,Schousboe, Arne,Krogsgaard-Larsen, Povl
, p. 895 - 908 (2007/10/03)
A series of lipophilic diaromatic derivatives of the glia-selective GABA uptake inhibitor (R)-4-amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol [(R)-exo-THPO, 4] were synthesized via reductive amination of 3-ethoxy-4,5,6,7-tetrahydrobenzo[d]isoxazol-4-one (9) or via N-alkylation of O-alkylatedracemic 4. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation or primary cultures of mouse cortical neurons and glia cells (astrocytes), as well as HEK cells transfected with cloned mouse GABA transporter subtypes (GAT1-4). The activity against isoniazid-induced convulsions in mice after subcutaneous administration of the compounds was determined. All of the compounds were potent inhibitors of synaptosomal uptake the most potent compound being (RS)-4-[N-(1,1-diphenylbut-1-en-4-yl)amino]-4,5,6,7-tetrahydrobenzo[d] isoxazol-3-ol (17a, IC50 = 0.14 μM). The majority of the compounds showed a weak preference for glial, as compared to neuronal, GABA uptake. The highest degree of selectivity was 10-fold corresponding to the glia selectivity of (R)-N-methyl-exo-THPO (5). All derivatives showed a preference for the GAT1 transporter, as compared with GAT2-4, with the exception of (RS)-4-[N-[1,1- bis(3-methyl-2-thienyl)but-1-en-4-yl]-N-methylamino]-4,5,6,7-tetrahydrobenzo[d] isoxazol-3-ol (28d), which quite surprisingly turned out to be more potent than GABA at both GAT1 and GAT2 subtypes. The GAT1 activity was shown to reside in (R)-28d whereas (R)-28d and (S)-28d contributed equally to GAT2 activity. This makes (S)-28d a GAT2 selective compound, and (R)-28d equally effective in inhibition of GAT1 and GAT2 mediated GABA transport. All compounds tested were effective as anticonvulsant reflecting that these compounds have blood-brain barrier permeating ability.
N6 -substituted adenosines for treating pain
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, (2008/06/13)
N6 -Substituted diarylalkyladenosines and pharmaceutically acceptable acid addition salts having highly desirable central nervous system and cardiovascular properties, processes for their manufacture and pharmaceutical compositions and methods for using said compounds and compositions are described.
