Synthesis of Tetrahydropyridinyltriazolothiadiazines as Possible Muscarinic Agonists

Amino-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiol 1 were condensed with 2-bromo-1- (substituted phenyl)ethanone to give pyridinyltriazolothiadiazines 2a^c, which were quaternarized with methyl iodide and oxidized with 30 % hydrogen peroxide to afford the corresponding methyl pyridinium salts 3a^c and pyridine-1-oxides 4a^c, respectively. The reduction of compounds 3 and 4 with NaBH4 in methanol produced the target compounds 1-methyl-1, 2, 5, 6-tetrahydropyridin-3- yl)-6-aryl-s-triazolothiadiazines 5a^c and 3-(1-hydroxyl-1, 2, 5, 6-tetrahydropyridin -3-yl)-6-aryl- s-triazolothiadiazines 6a^c, respectively. The endothelium vascular relaxing activity of the target compounds was screened.

Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels

Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath.The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System.The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis,respectively.Results:The total phenolic and total flavonoids contents of the extract were(267.75±5.77)mg GAE/g and(73.86±6.01)mg QE/g,respectively.Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC_(50)value of 0.016 mg/m L,which was blocked by atropine(0.3μM).Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC_(50)value of 2.185 mg/mL.Furthermore,Argemone mexicana extract relaxed potassium(80 mM)-induced contractions(EC_(50):9.07 mg/mL),similar to a standard drug verapamil.The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract(1-5 mg/mL)and verapamil(0.1-1μM).In addition,the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks.Conclusions:Argemone mexicana shows cholinergic agonist and calcium channel blocker activities,as well as antiemetic effect.It may be used as a potential agent for treating gastrointestinal disorders.

Synthesis and Bioactivity of Arecoline Derivatives Containing Amino-s-triazole Coupled Oxadiazole

5-（5＂-Substituted phenyl-[1＂,3＂,4＂]oxadiazol-2＂-yl methylsulfanyl）-3-pyridin-3′-yl- [1,2,4] triazol-4-yl amines la-j were quaternarized with methyl iodide to afford the corresponding methyl pyridinium salts 2a-j. The reduction of compounds 2 with NaBH4 in methanol gave the target compounds 5-（5＂-substituted phenyl-[1＂,3＂,4＂]oxadiazol-2＂-yl methylsulfanyl）-3-（1′-methyl-1＇,2＇,5＇,6＇-tetrahydropyridin-3＇-yl）-[1,2,4]triazol-4-ylamines 3a-j. The endothelium vascular relaxing activity of the target compounds were screened.

Synthesis and Their Endothelium Vascular Relaxation of Arecoline Derivatives Containing Oxadiazoline

Ten novel 1, 1-dimethyl-3-(2-or 5-aryl-4-acetyl-2, 3-dihydro-1, 3, 4-oxadiazoline-5-or- 2-yl)-1, 2, 5, 6- tetrahydropyridinium iodides were synthesized from starting material nicotinalde- hyde or nicotinic acid by two different synthetic methods respectively. The preliminary bioactive tests indicate som compounds exhibit potent relaxing effect on endothelial cells, comparable to Ach or arecoline.

Synthesis of 2-and 5-(1,1-Dimethyl-1,2,5,6-tetrahydropyridinium-3-yl)oxadiazoline Iodides

A series of 2- and 5-(1,1-dimethyl-1,2,5,6-tetrahydropyridinium-3-yl)oxadiazoline iodides, which might be used as M 1 muscarinic receptor agonists, was synthesized from nicotin-aldehyde and nicotinhydrazine, respectively. Their structures were characterized by 1H NMR, IR, MS spectra and elemental analysis.