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Background and purpose Cocamide monoethanolamide (CMEA) is commonly used as a surfactant-foam booster in cosmetic formulations. Upon contact with the eye or other sensitive skin areas, CMEA elicits stinging and lasting irritation. We hypothesized a specific molecular interaction with TRPV1 channels by which CMEA caused eye irritation. Experimental approach Eye irritancy was evaluated using eye-wiping tests in rabbits and mice. Intracellular Ca2+ concentrations and action potentials were measured using Ca2+ imaging and current clamp respectively. Voltage clamp, site-direct mutagenesis and molecular modelling were used to identify binding pockets for CMEA on TRPV1 channels. Key results CMEA-induced eye irritation is ameliorated by selective ablation of TRPV1 channels.Rodents exhibit much stronger responses to CMEA than rabbits. In trigeminal ganglion neurons, CMEA induced Ca2+ influx and neuronal excitability, effects mitigated by a TRPV1 channel inhibition and absent in TRPV1 knockout neurons. In HEK-293 cells expressing TRPV1 channels, CMEA increased whole-cell currents by increasing channel open probability (EC50 = 10.2 μM), without affecting TRPV2, TRPV3, TRPV4, and TRPA1 channel activities. Lauric acid monoethanolamide (LAMEA), the most abundant constituent of CMEA, was the most efficacious and potent TRPV1 channel activator, binding to the capsaicin-binding pocket of the channel. The T550I mutants of rabbit and human TRPV1 channels exhibit much lower sensitivity to LAMEA. Conclusions and implication CMEA directly activates TRPV1 channels to produce eye irritation. Rabbits, the standard animal used for eye irritancy tests are poor models for evaluating human eye irritants structurally related to CMEA. Our study identifies potential alternatives to CMEA as non-irritating surfactants.

A series of 7-alkoxy - [1,2,4] triazolo [1, 5-a] pyrimidine derivatives were designed and synthesized. Maximal electroshock (MES) and pentylenetetrazole (PTZ) tests were utilized to access their anticonvulsant activity. Most of the series of compounds exhibited significant anti-seizure effects. Further studies demonstrated that the anticonvulsant activity of these compounds mainly depended on their allosteric potentiation of GABA

In searching for more effective and safer antiepileptic drugs, a series of 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine-7(4H)-one derivatives were designed and synthesized. Spontaneous Ca

A facile synthesis of 1′,4′-dihydro-2′H-spiro[azetidin-2,3′-quinolin]-2′-one is described. Synthetic highlights include simultaneous construction of azetidine ring by intramolecular alkylation and formation of spirocarbon center in excellent yield plus removal of p-methoxybenzyl (PMB) amide protective group in mild condition with good yield.

A straightforward synthesis of 3,4,5-trisubstituted isoxazole derivatives via 1,3-dipolar cycloaddtion/SO2 extrusion of benzoisothiazole-2,2-dioxide-3-ylidenes with nitrile oxides is reported using 4 A molecular sieves as a dehydrochlorinating agent. This tandem ring closing/ring opening synthesis of 3,4,5-trisubstituted isoxazoles is the first of its kind. This methodology would enrich the synthetic chemistry of isoxazoles from easily available starting materials and benefit the discovery of novel isoxazoles with potential biological activities.

Figure 1 showed the performance of different nickel catalysts used for the amidation of phenylacetic acid and benzylamine in toluene at 110℃. And the catalytic activities of the different nickel catalysts were NiCl2>DPPE·NiCl2>(CH3COO)2Ni>Ni(acac)2>DPPP·NiCl2>NiCl2(Pph3)2>NiCl2·6H2O>none. ;Catalyst recyclability is an essential aspect of the green chemistry. Our best-performance direct amidation catalyst NiCl2 was found to be equally effective from fresh up to the 3rd and 3th cycle without significant loss of activity as showed in Figure 2. In the fourth cycle, the yield decreased obviously because of the loss of the catalyst. ;The influences of different solvents and reaction time on the direct amidation of phenylacetic acid with benzylamine catalysed by NiCl2 were investigated (Table 1). And from Table 1.;With the above knowledge in hand, we investigated the acid 1 and benzylamine 2 scopes of the NiCl2-catalysed direct amidation protocol at the same reaction condition. And the results showed in Table 2.;The original hydrogen spectra, carbon spectra and the mass spectra for all compounds

The new spirocyclic compounds, spiropyrrolidinyl-benzoisothiazoline derivatives were synthesized by the 1,3-dipolar cycloaddition of benzoisothiazole-2,2-dioxide-3-ylidenes and azomethine ylide. The stereochemistry of 1,3-dipolar cycloaddition as well as the stereochemistry of Knoevenagel condensation of benzoisothiazole-2,2-dioxide with aldehydes were studied.

A straightforward synthesis of 3,4,5-trisubstituted isoxazole derivatives via 1,3-dipolar cycloaddtion/SO2 extrusion of benzoisothiazole-2,2-dioxide-3-ylidenes with nitrile oxides is reported using 4 A molecular sieves as a dehydrochlorinating agent. This tandem ring closing/ring opening synthesis of 3,4,5-trisubstituted isoxazoles is the first of its kind. This methodology would enrich the synthetic chemistry of isoxazoles from easily available starting materials and benefit the discovery of novel isoxazoles with potential biological activities.

A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB-231 and Hep G2 cells were screened in vitro by an MTT assay. The results indicated that 13-member macrocycle 33 containing alkene chain showed the best results, exhibiting the highest inhibitory effects towards lung cancer cell line A549, which was higher than that of the reference cisplatin (IC50 value = 2.55 µmol/L).

This paper describes an eco-friendly and efficient direct amidation of benzylamine and phenylacetic acid derivatives in the presence of 10 mol% NiCl 2 as catalyst without any drying agent. For the different phenylacetic acid and benzylamine derivatives, the direct catalysed amidation gave moderate-to-excellent yields in toluene. The steric and electronic effects of substituent groups on the phenyl ring of acid were crucial to the yields of the direct amidation. The catalyst NiCl 2 can be recycled three times without loss of activity.

The reaction proceeds well and diastereoselectively with Z-configured 3-arylidene- and simple alkylidene-substituted benzoisothiazol-S,S-dioxides (I) and (IV).

To investigate the chemical constituents of the branches and leaves of (Jvariu kurzii.Compounds were isolated and purified by silica gel and Sephadex LH-20 column chromatography. Their chemical structures were identified on the basis of physicoc hemical properties and spectral data.Nineteen compounds were isolated and identified as: beta-sitosterol hexadecanoate (1), stigmasterol hexadecanoate (2), beta-acetylsitosterol (3), beta-acetylstigmasterul (4), tetratriacontanol (5), dotriacontanoic acid (6), beta-sitosterol (7), stigmasterol (8), 5alpha-stigmast-3 , 6-dione (9) , 5alpha-stigmast-22-ene-3,6-dione (10), vanillic acid (11), protocatechuic acid (12), N-(p-trans-collmaroyl) tyramine (13). kaempferol-3-O-beta-D-(6"-O-p-coumaryoyl) galactopyraunoside (14), kaempferol-3-O-rutinoide (15), rutin (16), daucosterol (17), L-quebrachitol (18), allantoin (19), respectively.Compounds 1-6, 9, 10, 13, 18, 19 were isolated from Annonaceac plants; Compounds 14-16 were obtained from the gemis Uvaria; an 7, 8, 11, 12, 17 were separated from this plant respectively for the first time.