1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists

Abstract

This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in vitro activity of these triazoles is further improved by inserting a methylene group between the central core and the carbonyl side chain. The most potent antagonists prepared in this series (IC(50)<20 nM) are the triazoles containing benzyl amides. These triazoles also show excellent selectivity between CB1 and CB2 receptors (IC(50)>10 microM for CB2; CB2/CB1>1000).

Synthesis and Antimalarial Activities of a Diverse Set of Triazole‐Containing Furamidine Analogues

“…[35][36][37] To synthesize the 4,5-disubstituted and the 1,4,5-and 2,4,5trisubstituted triazole units (Scheme 4), 4,4'-dicyanostilbene (22) was prepared as an intermediate for both series of compounds using Sonogashira reaction conditions between the 4bromobenzonitrile (21) and the 4-ethynylbenzonitrile (3) in the presence of palladium(II), copper(I) iodide and triethylamine. [47] The 1,4,5-trisubstituted triazole derivatives 25 a and 25 b were prepared using the copper(II)-catalyzed 1,3-dipolar cyclo- addition of azidobenzene 23 a or azidomethylbenzene 23 b to 4,4'-dicyanostilbene (22) at 65 8C, but the reaction did not work at this temperature probably due to steric hindrance; therefore, the temperature was increased to 120 8C. [32][33][34] The Pinner reaction was employed to obtain compounds 25 a and 25 b in yields of 22 % and 39 %, respectively, over two steps (Scheme 4).…”

“…[32][33][34] The Pinner reaction was employed to obtain compounds 25 a and 25 b in yields of 22 % and 39 %, respectively, over two steps (Scheme 4). [35][36][37] For the synthesis of 4,5-disubstituted derivative 27, 4,4'-dicyanostilbene (22) was allowed to react with sodium azide at reflux in DMF to give the triazole unit in 65 % yield (Scheme 4). [48] This reaction was attempted using the copper(I)catalyzed 1,3-dipolar cycloaddition, [32][33][34] but failed possibly because the sodium azide was degraded by the catalyst (no reaction with 1.0 equiv of NaN 3 , and only 25 % product 26 formation with 2.0 equiv).…”

“…ety of drugs have appeared in the literature. [14][15][16][17][18][19][20][21][22][23][24][25] Given the structural diversity possible within the triazole ring system, we aimed to produce an array of functionalized triazole-containing diamidines for structure-activity relationship (SAR) analysis. Sixteen different triazole derivatives with different substitution on the triazole and aromatic rings (para or meta) were prepared ( Figure 1): seven 1,4-substituted derivatives, two 1,5-substituted derivatives, two 2,4-substituted derivatives, and six 4,5-substituted derivatives.…”

Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances

“…However in vivo evaluation of the present 3,5-diphenylisoxazole series has not been reported yet. [45][46][47][48][49][50][51][52][53][54][55] and also because 1,4-diphenyl-1,2,3-triazoles showed geometrical resemblance to furamidine. It was observed that the cytotoxicities of triazoles were as lower compared to that of pentamidine and were not affected by the alkylation on the amidine groups or the substitution on the aromatic rings.…”

Synthesis and biological evaluation of novel d-glucose-derived 1,2,3-triazoles as potential antibacterial and antifungal agents

“…It is especially noteworthy that 1,2,3-triazole derivatives may be considered as new entry to azole antifungal agents (Aher et al, 2009). Also, some 1,2,3-triazole derivatives were used as DNA cleaving agents (Kamal et al, 2008), potassium channel activator (Calderone et al, 2008), and cannabinoid CB1 receptor (Hou et al, 2009) and so on. 1,2,3-Triazole was stable to metabolic degradation and capable of forming hydrogen bonds, which was favoring in binding of biomolecular targets and improving solubility (Horne et al, 2004;Lv et al, 2014).…”