Synthesis and biological activity of heterocycle-fused derivatives of pentacylic triterpenes as glycogen phosphorylase inhibitors / 中国药科大学学报

Aim: To search for novel modulators of glycogen metabolism through structural modifications of natural pentacyclic triterpenes. Methods: A series of N-heterocyclic derivatives were synthesized by fusing indole, qui-noxaline and pyrazine rings with A-ring of oleanolic and ursolic acids. The compounds were biologically evaluated for their inhibitory activity against rabbit muscle glycogen phosphorylase. Results and Conclusion: Twelve heter-ocyclic triterpene derivatives were synthesized and their structures were confirmed by IR, ~1H NMR, ~(13)C NMR and MS. Except for compound 12, all of the compounds exhibited glycogen phosphorylase inhibitory activity with IC_(50) values in the range of 14-252 μmol/L Among this series of compounds, compound 15 showed the best potency with IC_(50), of 14 μmol/L

Synthesis and Antihypertensive Activity of 1-Phenylethyl(or 3,4-Dimethyloxyphenylethyl)-4-substituted Aryloxypiperidines / 中国药科大学学报

AIM　The purpose is to make a search for new antihypertensive agents with higher activity and lower side effect. METHODS　As DDPH a lead compound, ten 1-Phenylethyl (or 3,4-dimethyloxyphenylethyl)-4-substituted aryloxypiperidine compounds were designed and synthesized, keeping the two structural fragments of DDPH: phenylethylamine and aryloxyalkylamine. Their structures were confirmed by Elemental Analysis, IR, 1H-NMR and Mass Spectrum. RESULTS　The majority of the compounds possessed potent antihypertensive activity and the antihypertensive effect of I3 and I4 was stronger than that of DDPH. CONCLUSION　The experimental results were accordant with designed thought and provided useful information for modifying the structure of DDPH deeply.

Effect of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethyl-amino) propanehydrochloride on cystometry and benign prostatic hyperplasia in rats / 中国药理学与毒理学杂志

1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride(DDPH) caused parallel rightward shifts of the phenylephrine(Phe) concentration-contractile response curves and did not suppress the maximal contractile response to Phe (pA2=7.24) in isolated rabbit urinary bladder smooth muscle. DDPH decreased the parameters of cystometry in urethane-anesthetized rats. Thirty minutes after DDPH (25 and 50 mg*kg-1 ig) administration, bladder capacity, voiding pressure, voiding threshold pressure were significantly decreased. With the observation of light-microscope and electron-microscope technique, DDPH (25 and 50 mg*kg-1*d-1 ig for 4 weeks) also inhibited the development of testosterone propionate-induced benign prostatic hyperplasia in rats. The results indicate that DDPH may inhibit benign prostatic hyperplasia and improve the urinary flow.

STUDY ON THE PHASE I METABOLITES OF PHONEPROLAMINE HYDROCHLORIDE IN RAT BILE BY LC/DAD/MSD / 药学学报

AIM　To study the phase I metabolites of phenoprolamine hydrochloride (DDPH) in rat bile. METHODS　DDPH was administered ip to bile duct-cannulated rats. Bile samples were collected before administration and up to 12 h after administration. After being treated with β-glucuronidase, the bile samples were purified and enriched with C-18 SPE columns, and then were analyzed by LC/DAD/MSD. The samples containing synthesized reference standards of DDPH metabolite 1-(2,6-dimethylphenoxy)-2-(3-methoxy-4-hydroxyphenylethylamino)-propane (M1), 1-(2,6-dimethyl-3-hydroxyphenoxy)-2-(3,4-methoxy-phenylethylamino)-propane (M2), 1-(2,6-dimethyl-4-hydroxyphenoxy)-2-(3,4-methoxyphenylethylamino)-propane (M3), 1-(2,6-dimethyl-4-hydroxyphenoxy)-2-(3-hydroxy-4-methoxyphenylethylamino)-propane (M4), 1-(2,6-dimethyl-3-hydroxyphenoxy)-2-(3-hydroxy-4-methoxyphenylethylamino)-propane (M5) and 1-(2,6-dimethyl-4-hydroxyphenoxy)-2-(3-methoxy-4-hydroxyphenylethylamino)-propane (M6) were analyzed by LC/DAD/MSD under identical conditions. RESULTS　The retention times, UV spectra, molecular weights and production spectra (obtained by collision-induced dissociation)of the apparent ions of peak A, B, C, D, E and F in the total ion chromatogram of DDPH treated rat bile sample were consistent with those of M1, M2, M3, M5, M4 and M6, respectively. CONCLUSION　M1, M2, M3, M4, M5 and M6 were identified as the phase I metabolites of DDPH in the rat.