6-氟-3-(4-哌啶基)-1,2-苯并异噁唑盐酸盐的合成

4-哌啶甲酸(2)与乙酐反应制得N-乙酰基-4-哌啶甲酸(3),3经历酰氯化、与间二氟苯Friedel-Crafts反应得到N-乙酰基-4-(2,4-二氟苯甲酰基)哌啶(4).4脱保护产物5与盐酸羟胺进行缩合反应生成(2,4-二氟苯基)-(4-哌啶基)甲酮肟盐酸盐(6).最后,6经分子内环合、成盐反应得精神病治疗药的中...     

慢性肾小球肾炎中药疗法临床研究

目的 探讨中药制剂治疗慢性肾小球肾炎临床效果。方法 选取我院2008年3月至2009年12月收治慢性肾小球肾炎患者56例,对症治疗基础上,给予院内自制中药制剂口服治疗3个月。结果 患者治疗3个月后,临床治愈15例,占26.79%;显效18例,占32.14%;有效16例,占28.57%;无效7例,占12.50%。结论 组方含有黄芪、白术、生地、茯苓、杜仲、熟地、桑寄生、当归,重在健脾益气、固摄精血。组方可调节机体免疫功能,扩张血管,降低血压,增加肾血流量,减少肾小球免疫复合物的沉积。通过提高机体免疫功能,降低尿蛋白,减轻肾脏病变,改善肾功能作用,保护肾脏。     

棘白霉素类抗真菌药的研究进展

棘白霉素类抗真菌药是一类新型抗真菌药,作用于真菌细胞壁,对于念珠菌属以及曲霉菌属均有效,而且安全性较高。目前已开发出卡泊芬净、米卡芬净和阿尼芬净3种该类抗真菌药。     

药物中抗坏血酸的铁铵矾氧化还原滴定法

研究了用磺基水杨酸作指示剂，用铁铵矾标准溶液氧化还原滴定抗坏血酸的新方法，用于药物中抗坏血酸的测定，结果与碘量测定法，紫外光度法所得结果基本一致。     

Anticancer Ruthenium(III) Complex KP1019 Interferes with ATP‐Dependent Ca2+ Translocation by Sarco‐Endoplasmic Reticulum Ca2+‐ATPase (SERCA)

Sarco‐endoplasmic reticulum Ca²⁺‐ATPase (SERCA), a P‐type ATPase that sustains Ca²⁺ transport and plays a major role in intracellular Ca²⁺ homeostasis, represents a therapeutic target for cancer therapy. Here, we investigated whether ruthenium‐based anticancer drugs, namely KP1019 (indazolium [trans‐tetrachlorobis(1H‐indazole)ruthenate(III)]), NAMI‐A (imidazolium [trans‐tetrachloro(1H‐imidazole)(S‐dimethylsulfoxide)ruthenate(III)]) and RAPTA‐C ([Ru(η⁶‐p‐cymene)dichloro(1,3,5‐triaza‐7‐phosphaadamantane)]), and cisplatin (cis‐diammineplatinum(II) dichloride) might act as inhibitors of SERCA. Charge displacement by SERCA adsorbed on a solid‐supported membrane was measured after ATP or Ca²⁺ concentration jumps. Our results show that KP1019, in contrast to the other metal compounds, is able to interfere with ATP‐dependent translocation of Ca²⁺ ions. An IC₅₀ value of 1 μM was determined for inhibition of calcium translocation by KP1019. Conversely, it appears that KP1019 does not significantly affect Ca²⁺ binding to the ATPase from the cytoplasmic side. Inhibition of SERCA at pharmacologically relevant concentrations may represent a crucial aspect in the overall pharmacological and toxicological profile of KP1019.     

Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing κP and κP,κS‐Coordinated Ph2PCH2CH2CH2S(O)xPh (x=0–2) Ligands

Iridium(III) complexes of the type [Ir(η⁵‐C₅Me₅)Cl₂{Ph₂PCH₂CH₂CH₂S(O)_xPh‐κP}] (x=0–2; 1 – 3 ) and [Ir(η⁵‐C₅Me₅)Cl{Ph₂PCH₂CH₂CH₂S(O)_xPh‐κP,κS}][PF₆] (x=0–1; 4 and 5 ) with 3‐(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph₂PCH₂CH₂CH₂S(O)_xPh were designed, synthesized, and characterized fully, including X‐ray diffraction analyses for complexes 3 and 4 . In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF‐7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC₅₀ values up to about 0.1 μM , representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal‐based anticancer agents.     

Peptide Bioconjugates of Electron‐Poor Metallocenes: Synthesis,Characterization, and Anti‐Proliferative Activity

We report the synthesis of metallocene compounds Cp₂M with two different electron‐withdrawing substituents on both cyclopentadienyl rings (hexafluoroacetone (HFA) and chlorobenzoyl ( 1 – 5 ); HFA and COOH ( 6 and 7 ), M=Fe or Ru). The COOH‐containing derivatives were used to synthesize peptide bioconjugates with enkephalin ( 8 and 9 ) and neurotensin ( 10 and 11 ) as well as fluorescein‐labeled neurotensin ( 12 ). All the molecules were fully characterized, including X‐ray structures for 6 and 7 . The physicochemical properties (lipophilicity and electrochemistry) and cytotoxicity on MCF‐7, HT‐29, and PT‐45 cancer cells were evaluated for selected compounds. Electrochemical investigation by cyclic voltammetry revealed that all bis‐substituted metallocenes are up to 300 mV harder to oxidize compared to the monosubstituted 2‐ferrocenylhexafluoropropan‐2‐ol (FcHFA: Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =214 mV; disubstituted derivatives: up to Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =512 mV; both vs. FcH^0/+). For the bis‐substituted compounds, log P determinations by RP‐HPLC showed increased lipophilicity in comparison to the monosubstituted FcHFA and RcHFA. Cellular uptake was investigated by fluorescence microcopy, and this revealed endosomal entrapment for 12 .     

Antivitamins for Medicinal Applications

Antivitamins represent a broad class of compounds that counteract the essential effects of vitamins. The symptoms triggered by such antinutritional factors resemble those of vitamin deficiencies, but can be successfully reversed by treating patients with the intact vitamin. Despite being undesirable for healthy organisms, the toxicities of these compounds present considerable interest for biological and medicinal purposes. Indeed, antivitamins played fundamental roles in the development of pioneering antibiotic and antiproliferative drugs, such as prontosil and aminopterin. Their development and optimisation were made possible by the study, throughout the 20th century, of the vitamins' and antivitamins' functions in metabolic processes. However, even with this thorough knowledge, commercialised antivitamin‐based drugs are still nowadays limited to antagonists of vitamins B₉ and K. The antivitamin field thus still needs to be explored more intensely, in view of the outstanding therapeutic success exhibited by several antivitamin‐based medicines. Here we summarise historical achievements and discuss critically recent developments, opportunities and potential limitations of the antivitamin approach, with a special focus on antivitamins K, B₉ and B₁₂.     

矿物药化学成分及药理研究进展

查阅大量相关文献,对近期矿物药的化学成分及药理研究概况进行综述。矿物药主要为一些天然产无机化合物晶体及其单质,不同的炮制方法往往影响其某些化学成分的含量及药效。此类药具有：抑茵、抗炎、抗肿瘤等多种药理活性。