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1.
Toshima H Oikawa H Yada H Ono H Toyomasu T Sassa T 《Bioscience, biotechnology, and biochemistry》2002,66(11):2504-2510
The labdane diterpene derivative, syn-copalol [(+)-5] is the alcohol part of syn-copalyl diphosphate [(+)-4]. In this paper, racemic (+/-)-5 was synthesized from a known racemic lactone in 8 steps. The current and our previous syntheses provide all four copalol derivatives [(+)-3, (-)-3 and (+/-)-5] which are required for the biosynthetic study of polycyclic diterpenes. 相似文献
2.
Kanakubo A Gray D Innocent N Wonnacott S Gallagher T 《Bioorganic & medicinal chemistry letters》2006,16(17):4648-4651
The synthesis of (+/-)-epiquinamide 1 and (+/-)-C(1)-epiepiquinamide 2 based on the use of a Curtius rearrangement to introduce the C(1) amino residue is reported. In a competition binding assay for [(3)H]epibatidine binding to rat brain membranes neither (+/-)-1 nor (+/-)-2 showed any significant level of nicotinic activity. 相似文献
3.
Takikawa H Hosoe S Ueda K Sasaki M 《Bioscience, biotechnology, and biochemistry》2004,68(9):1961-1965
The first synthesis of (+/-)-robinlin (1), a novel homo-monoterpene with strong bioactivity in the brine shrimp lethality test, was achieved by starting from 3-isobutyloxy-2,6,6-trimethyl-2-cyclohexen-1-one (2). 相似文献
4.
5.
In albino rats, infarctoid myocardial lesions were produced by intraperitoneal (i.p.) administration of isoproterenol (75 mg/kg, during 3 days). In other groups, the descending anterior left coronary artery was ligated. In both experimental settings, the intracerebroventricular (i.c.v.) administration of (+/-) propranolol (100-200-300 microg/animal/day, during 7 days) or (+/-) verapamil (40-80-160 microg/animal/day, during 7 days) afforded a significant protection (with the exception of the lowest dose) on the investigated parameters: arrhythmias, ischemic zone (in coronary ligated rats), lactate dehydrogenase and aspartate aminotransferase activity of the serum, focal necrosis (in isoproterenol treated rats). This protective activity is lower than that afforded by i.p. administered (+/-) propranolol (5 mg/kg, during seven days) or (+/-) verapamil (5 mg/kg, during seven days). From these data it may be concluded that (+/-) propranolol and (+/-) verapamil have a protective action on the experimental myocardial ischemia and necrosis in rats, not only when the drugs come in direct contact with the heart, but also acting upon the central nervous system. 相似文献
6.
Two trans-alpha,beta-dibenzyl-gamma-butyrolactone lignans carrying a hydroxyl group at the beta-benzylic carbon atom and a alpha-hydroxy alpha,beta-dibenzyl-gamma-butyrolactone lignan were synthesized in racemic form using the tandem conjugate addition reaction to construct the basic lignan skeleton. Subsequent reaction steps involved either a catalytic reduction of the regenerated keto group to the alcohol, or a hydrogenolysis to benzylic methylene followed by lactone enolate formation and oxidation to give the alpha-hydroxybutyrolactones. These procedures were applied for the synthesis of 7'-hydroxyenterolactones and 7'-hydroxymatairesinols, and 8-hydroxyenterolactones, respectively. The diastereomeric mixtures of these compounds were separated either by HPLC techniques or column chromatography and the structures were elucidated using NMR spectroscopy. 相似文献
7.
Taoda M Adachi YU Uchihashi Y Watanabe K Satoh T Vizi ES 《Neurochemistry international》2001,38(4):317-322
The presynaptic modulation of [3H]-noradrenaline (NA) release from rat kidney cortex slices, a method used for the first time, was investigated. Rat kidney cortex slices were loaded with [3H]-NA and the release of radioactivity at rest and in response to field stimulation was determined. The alpha(2)-adrenoceptor agonist, dexmedetomidine inhibited the stimulation-evoked release of NA from kidney slices in a concentration-dependent manner, whereas alpha(2)-adrenoceptor antagonist CH-38083 (7,8-methyenedioxy-14-alpha-hydroxyalloberbane HCl), an alpha(2)-adrenoceptor antagonists, enhanced it. When dexmedetomidine and BRL-44408, a selective alpha(2A) antagonist, were added together, the effect of dexmedetomidine was significantly antagonized. In contrast, ARC-239 (2-(2,4-(o-piperazine-1-yl)-ethyl-4,4-dimethyl-1,3-(2H, 4H)disoguinolinedione chloride), a selective alpha(2B)-antagonist, had no effect on the release and failed to prevent the effect of dexmedetomidine. Prazosin, an alpha(1)- and alpha(2B/C)-adrenoceptor antagonist enhanced the release evoked by field stimulation. It is therefore suggested that there is a negative feedback modulation of NA release at the sympathetic innervation of kidney cortex, and dexmedetomidine, a clinically used anesthetic adjunct inhibits the release via activation of alpha(2C)-adrenoceptors. 相似文献
8.
The synthesis and conformational studies of (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-allo-inositol and (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-6-O-methyl-allo-inositol are described. Solid state conformations of the title compounds have been studied by solving their X-ray crystal structures. The inositol ring in both the compounds deviate considerably from the ideal chair conformation to flattened chair conformation in the solid state. Their conformations in solution were studied by the use of 1H NMR spectroscopy. These conformational analyses revealed that the title compounds adopt similar conformations in solid and solution states irrespective of the solvent polarity. 相似文献
9.
Yohannes D Procko K Lebel LA Fox CB O'Neill BT 《Bioorganic & medicinal chemistry letters》2008,18(7):2316-2319
A novel fused tricyclic analog (11) of cytisine has been prepared (coined 'cyfusine') and determined to have high affinity at neuronal nicotinic acetylcholine receptors. A [3+2] cycloaddition protocol permitted entry into a 3,4-differentially difunctionalized dihydropyrrole (7). The penultimate cyclization was accomplished using the modified Van Tamelen conditions developed in our earlier synthesis of (+/-)-cytisine. Sequential ring-forming reactions ([3+2] cycloaddition/cyclopropanation/pyridone cyclization) gives a unique cyclopropyl analog (16) possessing a skeleton isoatomic with that of cytisine. 相似文献
10.
A simple and practical synthetic procedure for the versatile intermediates, (+/-)-1,2:5,6-di-O-isopropylidene-myo-inositol and (+/-)-6-O-benzoyl-1,2:4,5-di-O-isopropylidene-myo-inositol, is described. 相似文献
11.
N Yamaguchi 《Canadian journal of physiology and pharmacology》1985,63(11):1423-1428
The study was carried out to determine whether the diminished release of norepinephrine (NE) upon sympathetic activation in the presence of sotalol can be attributed to the blockade of beta-adrenoceptors in the liver. NE release from the liver was measured in hepatic venous blood collected during direct hepatic nerve stimulation in anesthetized dogs. The mean basal NE concentration in hepatic venous and aortic blood was 0.046 +/- 0.003 and 0.244 +/- 0.041 ng/mL, respectively. NE release increased significantly as stimulation frequency increased, while aortic NE concentration remained unchanged. The increasing response of NE release upon stimulation in the vehicle control group remained stable during the whole experimental period. In dogs treated with sotalol (5 mg/kg, i.v.), NE release was reduced approximately by 30-43%, and the difference was statistically significant (P less than 0.01) at 8 Hz. (+/-)-Propranolol (2.5 mg/kg, i.v.) tended to diminish it, but the difference was not significant. (-)-Propranolol (0.1 mg/kg, i.v.) did not alter NE release at any frequency tested. The beta-blocking action of these drugs in the liver, as determined by the antagonism against the hepatic arterial vasodilating response to isoproterenol, was most effective with (+/-)-propranolol (100%), followed by (-)-propranolol (90%) and sotalol (70%). The results suggest that the inhibitory effect of sotalol on NE release may be related to a mechanism other than its beta-blocking action in the dog liver. 相似文献
12.
Mukherjee S Prasad AK Parmar VS Howarth OW 《Bioorganic & medicinal chemistry letters》2001,11(16):2117-2121
(+/-)-5-Acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine has been synthesised by a highly diastereoselective [3+2] cycloaddition reaction between alpha-(4-fluorophenyl)-N-phenylnitrone and vinyl acetate in good yield. Candida rugosa lipase catalyses the deacetylation of this (+/-)-5-acetoxyisoxazolidine in a highly enantioselective fashion in diisopropyl ether containing n-butanol affording (-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine in 43% yield and >99% ee. 相似文献
13.
P-glycoprotein (Pgp) is an ATP-driven membrane exporter for a broad spectrum of hydrophobic xenobiotics. Pgp-overexpression is a common cause of multidrug resistance (MDR) in cancer cells and could lead to chemotherapeutic failure. Through an extensive herbal drug screening program we previously showed that (+/-)-praeruptorin A (PA), a naturally existing pyranocumarin isolated from the dried root of Peucedanum praeruptorum Dunn., re-sensitizes Pgp-mediated MDR (Pgp-MDR) cancer cells to cancer drugs. A number of PA derivatives were synthesized and one of these, (+/-)-3'-O, 4'-O-dicynnamoyl-cis-khellactone (DCK), was more potent than PA or verapamil in the reversal of Pgp-MDR. In Pgp-MDR cells DCK increased cellular accumulation of doxorubicin without affecting the expression level of Pgp. In Pgp-enriched membrane fractions DCK moderately stimulated basal Pgp-ATPase activity, suggesting some transport substrate-like function. However, DCK also inhibited Pgp-ATPase activity stimulated by the standard substrates verapamil or progesterone with decreased V(max)s but K(m)s were relatively unchanged, suggesting a primarily non-competitive mode of inhibition. While the binding of substrates to active Pgp would increase the reactivity of the Pgp-specific antibody UIC2, DCK decreased UIC2 reactivity. These results suggest that DCK could bind simultaneously with substrates to Pgp but perhaps at an allosteric site and thus affect Pgp-substrate interactions. 相似文献
14.
Kubota H Kakefuda A Watanabe T Taguchi Y Ishii N Masuda N Sakamoto S Tsukamoto Si 《Bioorganic & medicinal chemistry letters》2003,13(13):2155-2158
A series of (+/-)-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines were prepared and their bradycardic activities were examined in isolated guinea-pigs' right atria and in anesthetized rats. Modifications on the benzyl moiety of the parent compound, 1, led to the identification of compound 11e as a potent and specific bradycardic agent. 相似文献
15.
Su CR Damu AG Chiang PC Bastow KF Morris-Natschke SL Lee KH Wu TS 《Bioorganic & medicinal chemistry》2008,16(11):6233-6241
Due to their limited natural abundance and significant biochemical effects, we synthesized the alkaloids (+/-)-antofine (1a), (+/-)-deoxypergularinine (1b), and their dehydro congeners (2 and 3) starting from the corresponding phenanthrene-9-carboxaldehydes. We also evaluated their in vitro cytotoxic activity. Compounds 1a and 1b showed significant potency against various human tumor cell lines, including a drug-resistant variant, with EC(50) values ranging from 0.16 to 16ng/mL. Structure-activity correlations of these alkaloids and some of their synthetic intermediates were also ascertained. The non-planar structure between the two major moieties, phenanthrene and indolizidine, plays a crucial role in the cytotoxic activity of phenanthroindolizidines. Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom (1b). 相似文献
16.
Several radioactive analogues of abscisic acid have been tested for their growth-inhibitory effects and their metabolism in excised embryonic axes of Phaseolus vulgaris. The compounds tested were the methyl and ethyl esters of 2-14C-abscisic acid and the cis- and trans-1′,4′-diols of 2-14C-abscisic acid. All four compounds cause less growth inhibition than abscisic acid, and all four compounds are converted to abscisic acid in the axes at rates which are sufficient to account for most, if not all, of the observed growth-inhibitory activity. None of the four compounds is metabolized to the extent that abscisic acid is metabolized in the axes, suggesting that the structural requirements for growth-inhibitory activity and metabolism may be similar. 相似文献
17.
Okazaki R Oritani T Hara Y Yamamoto H 《Bioscience, biotechnology, and biochemistry》2001,65(4):943-946
Microbial hydroxylation of (+/-)-(2Z,4E)-5-(1',2'-epoxy-2',6',6'-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid (3a) with Cercospora cruenta, a fungus producing (+)-abscisic acid, gave a four-stereoisomeric mixture consisting of (+)- and (-)-xanthoxin acid (4a), and (+)- and (-)-epi-xanthoxin acid (5a) by an HPLC analysis with a chiral column. Screening of the microorganisms capable of oxidizing (+/-)-3a showed that Cunninghamella echinulata stereoselectively oxidized (+/-)-3a to xanthoxin acid (4a) with the some degree of enantioselectivity as (-)-3a to (-)-4a. 相似文献
18.
Of a range of glycerol analogues, (+/-)-2,3-dihydroxypropyl dichloroacetate (III) has been shown to be the most potent inhibitor of glycerol kinase in vitro. Inhibition is noncompetitive with a Ki value of 1.8 X 10(-3) M. The presence of ATP seems essential for effective inhibition of the enzyme, suggesting that the inhibitor is phosphorylated to a glycerol-3-phosphate analogue. In vivo III causes a decrease in the specific activity of liver glycerol kinase and produces a dose-dependent reduction in blood glucose levels. There is a reduction in the conversion of [U-14C] glycerol into glucose after administration of III to CBA/CA mice while gluconeogenesis from fructose is increased. This suggests that of the enzymes of gluconeogenesis only glycerol kinase is inhibited by III. This compound may be useful in reducing the lipid contribution to gluconeogenesis in advancing cancer. 相似文献
19.
New abscisic acid analogs possessing a cyano or methoxycarbonyl group at the 6'alpha-position of methyl abscisate were synthesized by regioselective hydrocyanation. These compounds had weak activity in the rice second leaf sheath elongation test. 相似文献
20.
Beta-adrenergic activity of (+/-)-hydroxybenzylisoproterenol in isolated rat fat cells and hepatocytes 总被引:1,自引:0,他引:1
C C Malbon 《Biochimica et biophysica acta》1981,673(2):203-216
The pharmacology of (+/-)-hydroxybenzylisoproterenol with respect to stimulation of cyclic AMP accumulation by isolated rat fat cells and liver cells was examined. (+/-)-Hydroxybenzylisoproterenol was found to be a full agonist and twice as potent as (-)-isoproterenol in liver cells, and equipotent to (-)-isoproterenol in fat cells with regard to stimulating cyclic AMP accumulation. A study of the ability of this catecholamine to stimulate adenylate cyclase activity of broken-cell preparations revealed that (+/-)-hydroxybenzylisoproterenol was equipotent to (-)-isoproterenol in liver cell homogenates, while 3- to 4-fold more potent than (-)-isoproterenol in fat cell ghost membranes. (+/-)-Hydroxybenzylisoproterenol was also found to be as potent as (-)-isoproterenol in stimulating cyclase activity of S49 mouse lymphoma cell membranes. Competition studies of specific [125I]iodohydroxybenzylpindolol binding to liver cell membranes revealed a Kd of 10 nM for (+/-)-hydroxybenzylisoproterenol and 25 nM for (-)-isoproterenol binding to the liver beta-adrenergic receptor. Competition studies of specific (-)-[3H]dihydroalprenolol binding to fat cell membranes indicated a similar affinity of these sites for both (+/-)-hydroxybenzylisoproterenol and (-)-isoproterenol. The guanyl nucleotide Gpp(NH)p induced a shift in the curve for competition of (-)-[3H]dihydroalprenolol binding by (-)-isoproterenol to the right, but failed to do so when (+/-)-hydroxybenzylisoproterenol was the competing agonist. Properties of (+/-)-[3H]hydroxybenzylisoproterenol binding to fat cell or liver cell membranes were inconsistent with those expected of adenylate cyclase coupled beta-adrenergic receptors. 相似文献