1094-91-3Relevant articles and documents
Development of novel LP1-based analogues with enhanced delta opioid receptor profile
Pasquinucci, Lorella,Turnaturi, Rita,Prezzavento, Orazio,Arena, Emanuela,Aricò, Giuseppina,Georgoussi, Zafiroula,Parenti, Rosalba,Cantarella, Giuseppina,Parenti, Carmela
, p. 4745 - 4752 (2017)
Pain relief achieved by co-administration of drugs acting at different targets is more effective than that obtained with conventional MOR selective agonists usually associated to relevant side effects. It has been demonstrated that simultaneously targeting different opioid receptors is a more effective therapeutic strategy. Giving the promising role for DOR in pain management, novel LP1-based analogues with different N-substituents were designed and synthesized with the aim to improve DOR profile. For this purpose, we maintained the phenyl ring in the N-substituent of 6,7-benzomorphan scaffold linked to an ethyl spacer bearing a hydroxyl/methyl or methoxyl group at carbon 2 or including it in a 1,4-benzodioxane ring. LP1 analogues were tested by competition binding assays. Compounds 6 (KiMOR = 2.47 nM, KiDOR = 9.6 nM), 7 (KiMOR = 0.5 nM and KiDOR = 0.8 nM) and 9 (KiMOR = 1.08 nM, KiDOR = 6.6 nM) retained MOR affinity but displayed an improved DOR binding capacity as compared to LP1 (KiMOR = 0.83 nM, KiDOR = 29.1 nM). Moreover, GPI and MVD functional assays indicated that compounds 6 (IC50 = 49.2 and IC50 = 10.8 nM), 7 (IC50 = 9.9 and IC50 = 11.8 nM) and 9 (IC50 = 21.5 and IC50 = 4.4 nM) showed a MOR/DOR agonist profile, unlike LP1 that was a MOR agonist/DOR antagonist (IC50 = 1.9 and IC50 = 1240 nM). Measurements of their antinociceptive effect was evaluated by mice radiant tail flick test displaying for compounds 6, 7 and 9 ED50 values of 1.3, 1.0 and 0.9 mg/kg, i.p., respectively. Moreover, the antinociceptive effect of compound 9 was longer lasting with respect to LP1. In conclusion the N-substituent nature of compounds 6, 7 and 9 shifts the DOR profile of LP1 from antagonism to agonism.
Benzocarbazoles dioxa like derivative and its application
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Paragraph 0074, (2016/12/01)
Provided are a benzodioxane compound as shown by the general formula (I), a pharmaceutical composition comprising same and the use thereof in treating psychotic and neuropathic diseases, particularly depression.
Rapid synthesis, screening, and identification of xanthone- And xanthene-based fluorophores using click chemistry
Li, Junqi,Hu, Mingyu,Yao, Shao Q.
supporting information; experimental part, p. 3008 - 3011 (2009/12/05)
A panel of new fluorophores with emission wavelengths from blue to yellow regions using the Cu(l)-catalyzed 1,3-dipolar cycloaddition reaction of alkyne-functionalized xanthones and xanthenes with various azides have been synthesized. Screening of the "cl
