15741-80-7Relevant academic research and scientific papers
Identification of a Potent Tryptophan-Based TRPM8 Antagonist with in Vivo Analgesic Activity
Bertamino, Alessia,Iraci, Nunzio,Ostacolo, Carmine,Ambrosino, Paolo,Musella, Simona,Di Sarno, Veronica,Ciaglia, Tania,Pepe, Giacomo,Sala, Marina,Soldovieri, Maria Virginia,Mosca, Ilaria,Gonzalez-Rodriguez, Sara,Fernandez-Carvajal, Asia,Ferrer-Montiel, Antonio,Novellino, Ettore,Taglialatela, Maurizio,Campiglia, Pietro,Gomez-Monterrey, Isabel
, p. 6140 - 6152 (2018/07/05)
TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N,N′-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC50 0.2 ± 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an icilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1-1 μg s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the S1-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.
Benzocarbazoles heterocyclic compound and its preparation and use (by machine translation)
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Paragraph 0106; 0108, (2016/10/07)
The present invention provides a class of non-nucleoside anti-viral inhibitors, in particular to such as shown in formula I benzo heterocyclic compound or its pharmaceutically acceptable salt or hydrate, the invention also provides the compound or its pharmaceutically acceptable salt or hydrate of the preparation method. Pharmacological test indicates that the compound or its pharmaceutically acceptable salt or hydrate can effectively inhibit hepatitis b virus DNA replication and hepatitis c virus RNA replication, therefore, the invention also provides the compounds in the preparation of preventing and/or the treatment of viral infections, particularly hepatitis b virus (HBV) infection, hepatitis c virus (HCV) infection of use of the medicament. (by machine translation)
Tryptamine-Based Derivatives as Transient Receptor Potential Melastatin Type 8 (TRPM8) Channel Modulators
Bertamino, Alessia,Ostacolo, Carmine,Ambrosino, Paolo,Musella, Simona,Di Sarno, Veronica,Ciaglia, Tania,Soldovieri, Maria Virginia,Iraci, Nunzio,Fernandez Carvajal, Asia,De La Torre-Martinez, Roberto,Ferrer-Montiel, Antonio,Gonzalez Muniz, Rosario,Novellino, Ettore,Taglialatela, Maurizio,Campiglia, Pietro,Gomez-Monterrey, Isabel
, p. 2179 - 2191 (2016/03/25)
Pharmacological modulation of the transient receptor potential melastatin type 8 (TRPM8) is currently under investigation as a new approach for the treatment of pain and other diseases. In this study, a series of N-substituted tryptamines was prepared to explore the structural requirements determining TRPM8 modulation. Using a fluorescence-based screening assay, we identified two compounds acting as an activator (2-(1H-indol-3-yl)-N-(4-phenoxybenzyl)ethanamine, 21) or an inhibitor (N,N-dibenzyl-2-(1H-indol-3-yl)ethanamine, 12) of calcium influx in HEK293 cells. In patch-clamp recordings, compound 21 displayed a significantly higher potency (EC50 = 40 ± 4 μM) and a similar efficacy when compared to menthol; by contrast, compound 12 produced a concentration-dependent inhibition of menthol-induced TRPM8 currents (IC50 = 367 ± 24 nM). Molecular modeling studies using a homology model of a single rat TRPM8 subunit identified a putative binding site located between the VSD and the TRP box, disclosing differences in the binding modes for the agonist and the antagonist.
Tryptamine derivatives as novel non-nucleosidic inhibitors against hepatitis B virus
Qu, Shi-Jin,Wang, Gui-Feng,Duan, Wen-Hu,Yao, Shan-Yan,Zuo, Jian-Ping,Tan, Chang-Heng,Zhu, Da-Yuan
experimental part, p. 3120 - 3127 (2011/06/24)
A series of tryptamine derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the HepG2.2.15 cell line. The preliminary SAR was discussed. Compounds 2e and 4a showed potent antiviral activity (IC50 = 0.4 and 50 = 40.6 and >25 μM, respectively).
Total syntheses of enantiomerically enriched R-(+)- And S-(-)-deplancheinef
Sydorenko, Nadiya,Zificsak, Craig A.,Gerasyuto, Aleksey I.,Hsung, Richard P.
, p. 2140 - 2144 (2007/10/03)
Total syntheses of indoloquinolizidine alkaloid (±)-, R-(+)-, and S-(-)-deplancheine are described here. The synthesis features an enantioselective intramolecular formal aza-[3 + 3] cycloaddition for the construction of the quinolizidine CD-ring. This application serves to introduce a new synthetic strategy for the synthesis of indoloquinolizidine alkaloids. The Royal Society of Chemistry 2005.
Total syntheses of strychnan- and aspidospermatan-type alkaloids. 2. Generation of 15-(3-furanyl) ABCE tetracyclic intermediates
Parsons,Berk,Kuehne
, p. 7482 - 7489 (2007/10/02)
The synthesis of Nb-benzyl-2-(dimethyl 2-malonyl)- and 2-(methyl 2- acetyl)tryptamines (21, 25) provides access to methyl 4-(3-furanyl)- 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (12) and methyl 3- benzyl-5-(3-furanyl)-2,3,3a,4,5,
