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991.
5-甲基-7,4’-二羟基异黄酮水溶性衍生物的合成及其抗缺氧活性 总被引:4,自引:0,他引:4
目的5-甲基-7,4’-二羟基异黄酮水溶性衍生物的合成及其抗缺氧活性的比较。方法三氟化硼-乙醚催化的“一锅法”工艺制备母体化合物1,并通过甲基化和磺化反应合成衍生物2~4,常压耐缺氧试验评价其活性。结果化合物3和4水溶性强,且抗缺氧作用等价于母体化合物。结论新合成的水溶性化合物3和4具有明显的抗缺氧活性。 相似文献
992.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(5):459-464
The potent peroxisome proliferator‐activated receptor (PPAR) δ ligand L783483 (3‐chloro‐4‐(3‐(7‐propyl‐3‐trifluoromethyl‐benzisoxazol‐6‐oxy)propylsulfanyl)phenylacetic acid) has been labelled with tritium via selective tritium/bromine exchange of 5‐bromo‐6‐(3‐bromopropyloxy)‐7‐propyl‐3‐trifluoromethyl‐benzisoxazole. [3H]‐L783483 had a specific activity of 529 GBq/mmol (14.3 Ci/mmol) and a radiochemical purity of 98%. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
993.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(9):883-892
The MMPI [14C]ABT‐770 (1) , N‐[(1S)‐1‐[(4,4‐Dimethyl‐2,5‐dioxo‐1‐imi‐dazolidinyl)methyl]]‐2‐[[4′‐(trifluoromethoxy)[1,1′‐biphenyl]‐4‐yl]oxy]ethyl]‐N‐hydroxyformamide was synthesized in 8 steps using 4‐bromophenol‐UL‐14C (10) as a starting material. The Carbon‐14 label was introduced in one of the metabolically stable biphenyl rings. The key sequence of the synthesis was a three‐step one‐pot reaction in which the hydantoin moiety was introduced, the imine oxidized and further hydrolyzed to get the penultimate precursor to [14C]ABT‐770 (1) in 56% yield. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
994.
Mano M Arakawa T Mano H Nakagawa M Kaneda T Kaneko H Yamada T Miyata K Kiyomura H Kumegawa M Hakeda Y 《Calcified tissue international》2000,67(1):85-92
Prostaglandins (PGs) are well known to be important local factors in regulating bone formation and resorption. PGE2 is a potent stimulator of bone resorption because of enhancing osteoclast formation by its indirect action through stromal
cells. However, the direct action of PGE2 on functionally mature osteoclasts is still controversial. In this study using highly purified rabbit mature osteoclasts,
we examined the direct effect of PGE2 on osteoclastic bone-resorbing activity and its mechanism. PGE2 inhibited resorption pit formation on a dentine slice by the purified osteoclasts in a dose- and time-dependent manner. The
inhibitory effect appeared as early as 4 hours after the PGE2 addition. Forskolin and 12-0-tetradecanoyl phorbol-13-acetate (TPA), respective activators of adenylate cyclase and protein
kinase C, also decreased the osteoclastic bone-resorbing activity. PGE2 increased the content of intracellular cAMP in a dose range effective for the inhibition of bone resorption, whereas the
prostanoid did not alter the intracellular level of inositol triphosphate. The inhibition of osteoclastic bone resorption
by PGE2 was amplified and diminished by a cAMP phosphodiesterase inhibitor (isobutyl methylxanthine) and a protein kinase A inhibitor
(Rp-cAMP), respectively. Of four different subtypes of PGE2 receptors (EPs), EP4 mRNA was predominantly expressed in isolated osteoclasts, whereas the other types of EP mRNA were detected
in only small amounts. These results suggest that the PGE2 inhibitory effect was mediated by an adenylate cyclase system coupled with EP4. This possible association of PGE2 with EP4 in mature osteoclasts was supported by the finding that a specific agonist of EP4 (AE-604) inhibited the bone-resorbing
activity and elevated the intracellular cAMP content. However, butaprost, a selective EP2 agonist, also mimicked the PGE2 effects on isolated osteoclasts although EP2 mRNA expression was minimal. In conclusion, PGE2 directly inhibits bone-resorbing activity of functionally mature osteoclasts by activation of the adenylate cyclase system,
perhaps mainly through EP4.
Received: 21 July 1999 / Accepted: 31 January 2000 相似文献
995.
996.
针刺对实验性变态反应性神经炎TNF-α和IL-4的影响 总被引:2,自引:0,他引:2
目的 探讨肿瘤坏死因子-α(TNF-α)和白细胞介素-4(IL-4)与实验性变态反应性神经炎(EAN)发病的关系,从细胞因子水平研究针刺疗法对本病的免疫调节作用。方法 40只大鼠分为正常对照组、模型组、针刺组、药物组,建立大鼠EAN动物模型,观察大鼠发病率及致病程度,针刺组取腰。夹脊、足三里、悬钟穴,药物组用泼尼松灌胃给药。采用双抗体夹心ELISA法,检测大鼠血清的TNF-αa和IL-4的含量变化。结果 模型组TNF-α含量较正常组明显升高。针刺组和药物组均能降低TNF-α的含量,使其水平接近正常,尤以药物组抑制作用明显。IL-4的含量各组间均无明显差异。结论 提示本病存在Th1/Th2细胞因子间的失衡,其中以Th1型细胞占优势。针刺主要是通过抑制TNF-α等Th1细胞,来重建细胞因子间的平衡。 相似文献
997.
Abstract: There is evidence to indicate that opioid compounds with mixed μ agonist/δ antagonist properties are analgesics with low propensity to produce tolerance and physical dependence. A chimeric peptide containing the potent and selective μ agonist H‐Dmt‐D‐Arg‐Phe‐Lys‐NH2 ([Dmt1]DALDA) (Dmt = 2′,6′‐dimethyltyrosine) and the potent and selective δ antagonist H‐Tyr‐TicΨ[CH2‐NH]Cha‐Phe‐OH (TICP[Ψ]) (Cha = cyclohexylalanine), connected ‘tail‐to‐tail’ via a short linker, was synthesized using a combination of solid‐phase and solution techniques. The resulting peptide, H‐Dmt→D‐Arg→Phe→Lys‐NH‐CH2‐CH2‐NH‐Phe←Cha[NH‐CH2]ΨTic←Tyr‐H, showed the expected μ agonist/δ antagonist profile in the guinea‐pig ileum and mouse vas deferens assays. Its μ and δ receptor binding affinities were in the low nanomolar range, as determined in rat brain membrane binding assays. 相似文献
998.
H. Lboutounne Y. C. Guillaume L. Michel S. Makki Ph. Humbert J. Millet 《Drug development research》2004,61(2):86-94
Trimethylpsoralen (TMP) is often used to treat skin diseases (i.e., psoriasis, vitiligo, etc.). This drug permeates moderately the skin barrier. In the present study, we investigated the effect of formulation on the improvement of TMP skin bioavailability. Three formulations were performed. Each form (liposomes, nanospheres, and EtOH solution) contained 0.05% of TMP. For each preparation, the quantity deposited on the skin surface was 250 µg (Q0). The TMP percutaneous penetration through ex‐vivo human skin was processed by Franz® cells (n=4) using a human albumin solution (1.4% w/v) as receiver medium. The percentages of the extracted TMP that permeated through the skin and that were retained in the skin over 24 h, were calculated with respect to Q0. The values obtained were reported, respectively, as follows: EtOH solution (1.33 vs. 0.08%), liposomes (0.93 vs. 0.93%), and PLG‐nanospheres (0.79 vs. 3.01%). So, considering the correlation between the cumulated amounts of TMP permeated through the skin and the TMP stocked in the skin, the nanosphere form showed the higher quantity of TMP accumulated in the skin structures. On the other hand, the maximum value of the flux (ng/cm2/h) in the steady state of TMP incorporated in each formulation was at 6 h for all formulations: 173.5±1.06 (EtOH solution) > 120.4±1.06 (liposomes) > 93.82±0.88 (PLG‐nanospheres). These results indicate that the controlled release of TMP by incorporation in PLG‐nanospheres may increase drug content in the skin, while maintaining a minimal percutaneous absorption. Finally, this work shows that the PLG‐nanospheres could constitute a promising approach for controlling TMP release in order to maintain its topical activity. Drug Dev. Res. 61:86–94, 2004. © 2004 Wiley‐Liss, Inc. 相似文献
999.
目的 观察中药金三莪对实验性肝纤维化大鼠小肠通透性的影响及其作用机制。方法 将大鼠分为A ,B ,C 3组 ,B组和C组采用四氯化碳造模 ,C组于造模第 4周开始灌胃中药金三莪 ,A组和B组灌胃生理盐水 ,共 4周。观察各组大鼠肝功能 ,血清内毒素、D -乳酸、二胺氧化酶 (DAO)及光镜下肝和小肠组织的病理改变。结果 C组大鼠血清ALT及AST值降低 ,肝小叶结构趋于正常 ,纤维间隔变薄 ,血清内毒素、D -乳酸、DAO水平减低 ,与B组比较有显著性差异。结论 中药金三莪能有效保护肠黏膜 ,阻止肠通透性增加 ,可减轻四氯化碳诱导肝纤维化大鼠的肝损伤及纤维化程度。 相似文献
1000.
目的 :研究消风散颗粒免疫调节作用和机制。方法 :分别观察了消风散颗粒对小鼠迟发型变态反应 (DTH)耳肿胀度、胸腺指数、脾指数 ;丝裂原诱导的脾T、B淋巴细胞增殖和炎症组织细胞因子的影响。结果 :消风散颗粒可降低DTH小鼠异常增高的耳肿胀度、脾指数和胸腺指数 ;抑制丝裂原诱导的脾T、B淋巴细胞增殖 ;抑制炎症组织细胞因子白介素 1 (IL 1 )、白介素 2 (IL 2 )和白介素 4 (IL 4 )的活性。结论 :消风散颗粒的免疫抑制作用与其调节T、B淋巴细胞功能和抑制炎性细胞因子的活性有关。 相似文献