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991.
Naiara VázquezVanessa Gómez-Vallejo Javier CalvoDaniel Padro Jordi Llop 《Tetrahedron letters》2011,52(5):615-618
Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers. In the current Letter, analogs of enantiomeric substituted benzamides (Raclopride and FLB-457) in which the phenyl ring has been substituted by a carborane cage (either orto- or meta-carborane) have been developed as potential D2 receptor antagonists. The formation of intramolecular hydrogen bonds (in solution) and the stability of the new chemical entities have been evaluated by means of 1H NMR and HPLC-MS, respectively. 相似文献
992.
Manuela Weber Herbert Bartsch Thomas Erker 《Monatshefte für Chemie / Chemical Monthly》2002,133(5):653-659
Summary. Starting from 2-chloro-3-nitropyridine, 2-isopropyl-1,4-dihydropyrido[2,3-b]pyrazin-2(3H),3-dione was synthesized. This compound was reacted with potassium tert-butoxide and diethyl chlorophosphate to afford an intermediate dihydropyrido[2,3-b]pyrazin-2-ylphosphate derivative which in turn furnished the desired 1,2,4-oxadiazolylimidazo[1,5-a]pyrido[2,3-e]pyrazine derivatives with 5-alkyl-3-isocyanomethyl-1,2,4-oxadiazoles in the presence of additional tert-butoxide. The title compounds are potential ligands for the γ-aminobutyric acid A/benzodiazepine receptor complex.
Received November 26, 2001. Accepted December 3, 2001 相似文献
993.
《中国化学》2018,36(2):129-133
The sulfoximine group has been evaluated as a pharmacophore. Introducing the sulfoximine structure into medicinal compounds as exciting motifs has brought opportunities in drug discovery. In order to develop new ryanodine receptor (RyR) modulators, a series of phthalamides containing sulfoximine derivatives were designed, synthesized, and evaluated against oriental armyworm and diamondback moth for their insecticidal activities. These studies helped to elucidate the electronic and structural requirements around the sulfoximine motif for insecticidal activity. All new structures were synthesized and characterized by 1H NMR, 13C NMR, HRMS and bioassay and a preliminary structure − activity relationship (SAR) was discussed. The biological assessment indicated that most title compounds showed good to excellent larvicidal activities. Compounds Ia , Ie , and If gave excellent insecticidal activity against oriental armyworm, which showed 100% larvicidal activity at 0.5 mg/L. All compounds showed 100% larvicidal activity at 0.1 mg/L against diamondback moth. In particular, the larvicidal activities of Ie , If , and Ih at 0.0001 mg/L were 50%, 20%, and 40%, respectively, reaching an activity as high as that of the commercial flubendiamide (40%, 0.0001 mg/L). Therefore, Ia , Ie , If and Ih could be considered as new lead structures for the development of new ryanodine receptor (RyR) modulators. 相似文献
994.
含酰肼结构荧光受体的合成及其阴离子识别研究 总被引:1,自引:0,他引:1
合成了一种新型的含蒽荧光基团和酰肼结构的阴离子受体,经过核磁共振氢谱(1HNMR)、质谱(MS)、红外光谱(IR)等检测方法证实其结构.用荧光光谱法研究了该阴离子受体与不同阴离子(AcO-,H2PO-4,Cl-,Br-,I-)的相互作用.结果表明:该阴离子受体与AcO-具有很好的选择性识别配位性能,对不同阴离子的络合选择性次序为:AcO->H2PO-4形成1∶1的络4 Cl-,Br-,I-.荧光光谱数据说明该阴离子受体可与AcO-,H2PO-合物. 相似文献
995.
Epidermal growth factor receptor (EGFR) is an attractive target for tumor therapy because it is overexpressed in the majority of solid tumors and the increase in receptor expression levels has been linked with a poor clinical prognosis. Also it is well established that blocking the interaction of EGFR and the growth factors could lead to the arrest of tumor growth and possibly result in tumor cell death. A13 is a murine monoclonal antibody (mAb) that specifically binds to various sets of EGFR-expressing tumor cells and inhibits EGF-induced EGFR phosphorylation. We isolated human immunoglobulin genes by guided selection based on the mAb A13. Four different human single chain Fvs (scFvs) were isolated from from hybrid scFv libraries containing a human VH repertoire with the VL of mAb A13 and a human VL repertoire with the VH of mAb A13. All the 4 scFvs bound to EGFR-expressing A431 cells. One scFv (SC414) with the highest affinity was converted to IgG1 (ER414). The ER414 exhibited ~17 fold lower affinity compared to the A13 mAb. In addition the ER414 inhibited an EGF-induced tyrosine phosphorylation of EGFR with much lower efficacy compared to the A13 mAb and Cetuximab (Merck KgaA, Germany). We identified that the epitope of A13 mAb is retained in ER414. This approach will provide an efficient way of converting a murine mAb to a human mAb. 相似文献
996.
Type 1 diabetes mellitus is caused by the autoimmune destruction of β cells within the islets. In recent years, innate immunity has been proposed to play a key role in this process. High-mobility group box 1 (HMGB1), an inflammatory trigger in a number of autoimmune diseases, activates proinflammatory responses following its release from necrotic cells. Our aim was to determine the significance of HMGB1 in the natural history of diabetes in non-obese diabetic (NOD) mice. We observed that the rate of HMGB1 expression in the cytoplasm of islets was much greater in diabetic mice compared with non-diabetic mice. The majority of cells positively stained for toll-like receptor 4 (TLR4) were β cells; few α cells were stained for TLR4. Thus, we examined the effects of anti-TLR4 antibodies on HMGB1 cell surface binding, which confirmed that HMGB1 interacts with TLR4 in isolated islets. Expression changes in HMGB1 and TLR4 were detected throughout the course of diabetes. Our findings indicate that TLR4 is the main receptor on β cells and that HMGB1 may signal via TLR4 to selectively damage β cells rather than α cells during the development of type 1 diabetes mellitus. 相似文献
997.
目的探讨呼吸机相关性肺炎(VAP)患者支气管肺泡灌洗液中可溶性髓系细胞触发受体-1(sTREM-1)的动态变化及其临床意义.方法选择临床疑诊VAP患者112例,通过微支气管肺泡灌洗技术获取其BALF液体,测定其BALF中sTREM-1、血清CRP水平及临床肺部感染积分(CPIS).动态观察确诊的74例VAP患者在入组第1、4、7、14天(或脱机/死亡当天)BALF中sTREM-1、血清CRP水平及CPIS变化趋势,并比较存活者(39例)与死亡者(35例)各指标的差异.结果 VAP组与非VAP组在临床疑诊当天BALF中sTREM-1、血清CRP水平及CPIS评分明显升高,差异有统计学意义(P<0.01).ROC曲线分析显示BALF中sTREM-1水平在153.18pg/ml时,诊断VAP有最佳的敏感性和特异性,分别为86.49%和84.21%,ROC曲线下面积为0.882.VAP组中存活者BALF中sTREM-1水平在第7天已经下降,第14天或脱机前已经降至非 VAP组水平,VAP组死亡者 BALF中sTREM-1水平在第7、14天或死亡前持续增高,与存活者在相同时间点比较差异有统计学意义(P<0.01).VAP组 BALF中sTREM-1水平与APACHEII评分呈正相关(r=0.526, P<0.01).结论 BALF中sTREM-1水平在>153.18pg/ml时,有利于早期诊断VAP;VAP患者BALF中sTREM-1水平变化与病情的严重程度及预后相关. 相似文献
998.
《Analytical letters》2012,45(8-9):609-619
Abstract We describe here a competitive protein-binding assay (CPBA) of cAMP which employs a crude thyroid cytosol preparation as the ligand-binding reagent. The affinity constant (Ka) of the binding of cAMP to the thyroid receptor varied between 1 and 4 × 109 M?1 in the assay. ATP, ADP and AMP did not interfere in the assay. Cross -reaction of cGMP, 1.8%, and that of cIMP, 36%, were comparable to those observed with previously described CPBAs of cAMP. The range of the assay standard curve was 0.5—20.0 pmoles per tube. Coefficient of variation was 8.3% within an assay and 8.7% between assays. The assay was applied to measurement of cAMP in biologic fluids and tissues. The results were comparable to those obtained with previous methods. 相似文献
999.
1000.
《Journal of Coordination Chemistry》2012,65(24):3951-3960
We designed and synthesized a Cu-coordination complex based on a seven-membered amide cycle and studied its binding ability with nucleotides (cytidine 5′-monophosphate (CMP), cytidine 5′-diphosphate (CDP), cytidine 5′-triphosphate (CTP), cytidine d-5′-monophosphate (dCMP), and thymidine d-5′-monophosphate (dTMP)) by UV-Vis spectroscopy. Results indicate that the compound shows the highest binding ability with CDP among the studied nucleotides and can selectively and strongly bind nucleotides in neutral aqueous solution. The compound can be used as optical receptor for the detection of CDP. 相似文献