102951-77-9Relevant 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)
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.
Indole derivatives and anti-ulcer compositions thereof
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, (2008/06/13)
Disclosed are indole derivatives of formula (I) STR1 wherein Y represents H, C1 -C6 alkyl, C1 -C6 alkoxy or halogen; Z represents --CH2 N(R5)--; R represents H or --CH2 CH2
