193825-63-7Relevant academic research and scientific papers
Synthesis, β-adrenergic receptor binding and antihypertensive potential of vanillin-derived phenoxypropanolamines
Coumar, Mohane S.,Jindal, Dharam P.,Bruni, Giancarlo,Massarelli, Paola,Singh, Randhir,Sharma, Amit K.,Nandakumar,Bodhankar, Subhash L.
, p. 903 - 909 (2008/12/23)
Synthesis of vanillin-derived phenoxypropanolamines is carried out by condensing 4-hydroxy-3-methoxybenzaldehyde (vanillin) 1 with epichlorohydrin, followed by treatment with iso-propylamine or tert-butylamine to open the epoxy ring. Percentage inhibition of [3H]dihydroalprenolol binding to both β1- and β2-adrenergic receptors by the newly synthesized compounds is assessed in vitro using turkey erythrocyte membrane (β1) and lung homogenate of rats (β2). Formyl derivatives 8 and 9 showed maximum inhibitory effect in binding assay and are non-selective similar to propranolol. On the other-hand, aldoxime compounds 10 and 11 have preference for β1adrenergic receptors similar to atenolol. Also four of the compounds 8-11 are evaluated for their anti-hypertensive potential, in left renal artery ligation and fructose induced hypertension models. 4-(3-tert-Butylamino-2-hydroxy-propoxy)-3-methoxy- benzaldehyde oxime 11 shows antihypertensive effect better than propranolol.
The new generation dihydropyridine type calcium blockers, bearing 4-phenyl oxypropanolamine, display α-/β-adrenoceptor antagonist and long-acting antihypertensive activities
Liang, Jhy-Chong,Yeh, Jwu-Lai,Wang, Chia-Sui,Liou, Shwu-Fen,Tsai, Chieh-Ho,Chen, Ing-Jun
, p. 719 - 730 (2007/10/03)
A new series of dihydropyridine derivatives, bearing oxypropanolamine moiety on phenyl ring at the 4-position of the dihydropyridine base, were prepared. Oxypropanolamine was synthesized by replacing the phenolic OH of vanillin or other compounds, having a phenyl aldehyde group, with epichlorohydrin, followed by cleavaging the obtained epoxide compounds with tert-butylamine, n-butylamine or 2-methoxy-1-oxyethylamino benzene (guaiacoxyethylamine), respectively. Obtained various oxypropanolamine compounds, still remaining a phenyl aldehyde moiety, were then performed by Hantzsch condensation reaction with methylacetoacetate or ethylacetoacetate, respectively, to give our new series of dihydropyridine linked with the 4-phenyl ring. These compounds were evaluated for inotropic, chronotropic, and aorta contractility that associated with calcium channel and adrenoceptor antagonist activities. Dihydropyridine derivatives that with oxypropanolamine side chain on their 4-phenyl ring associated α-/β-adrenoceptor blocking activities created a new family of calcium entry and the third generation β-adrenoceptor blockers. Optimizing this research to obtain more potent α-/β-adrenoceptor blocking and long-acting antihypertensive oxypropanolamine on the 4-phenyl ring of dihydropyridine series compounds was thus accomplished and classified as third generation dihydropyridine type calcium channel blockers, in comparison with previous short-acting type nifedipine and long-acting type amlodipine. We concluded that compounds 1a, 1b and 1g showed not only markedly high calcium-antagonistic activity but also the highest antihypertensive effect; compounds 1b, 1c, 1f, 1g, 1i and 1j induced sustained antihypertensive effects are major and attributed to their calcium entry and α-adrenoceptor blocking activities in the blood vessel due to their introduction of 2-methoxy, 1-oxyethylamino benzene moiety in the side chain on the 4-phenyl ring of dihydropyridine. Bradycardiac effects of all the compounds 1a-1j resulted from calcium entry and β-adrenoceptor blocking, which attenuate the sympathetic activation-associated reflex tachycardia in the heart. We selected compound 1b as candidate compound for further pharmacological and pre-clinical evaluation studies.
A new aspect of view in synthesizing new type β-adrenoceptor blockers with ancillary antioxidant activities
Huang, Yeun-Chih,Wu, Bin-Nan,Yeh, Jwu-Lai,Chen, Sheue-Jiun,Liang, Jyh-Chong,Lo, Yi-Ching,Chen, Ing-Jun
, p. 1739 - 1746 (2007/10/03)
A series of vanilloid-type β-adrenoceptor blockers derived from traditional Chinese herbal medicines were synthesized and tested for their antioxidant and adrenoceptor antagonistic activities. They all possessed significant β-adrenoceptor blocking activities under in vitro experiments and radioligand binding assays. In addition, some compounds were further examined in in vito tests and produced antagonist effects matching that of propranolol and labetalol by measurements of antagonism toward (-)isoproterenol-induced tachycardia and (-)phenylephrine-induced pressor responses in anesthetized rats. Furthermore, all of the compounds had antioxidant effects inherited from their original structures. In conclusion, compound 11 had the most potent β-adrenoceptors blocking activity, 12 and 13 possessed high cardioselectivity, whereas 14, 15 and 16 possessed additional α-adrenoceptor blocking activity and 15 is the most effective antioxidant of all. the antioxidant activity may be due to their @α and β unsaturated side chain at position 1 and ortho-substituted methoxy moiety on 4-phenoxyethylamine. Copyright
