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1.
双环[1.1.1]戊烷(BCP)是一种具有三维立体结构的桥环骨架,其作为苯环、叔丁基和炔烃的生物电子等排体,已经在药物化学领域得到广泛的应用。随着BCP应用范围的扩大,BCP及其衍生物的合成日益成为研究的热点。本文对BCP衍生物的主要合成策略和方法进行总结,旨在为新药研发人员提供参考。 相似文献
2.
Claudia Enrichi Cristiano Zanetti Rosaria Stabile Carla Carollo Luca Ghezzo Francesco Piccione 《The journal of spinal cord medicine》2020,43(5):710-713
Context: Magnetic Resonance Imaging (MRI) is an essential diagnostic tool for neuroimaging tissues such as the spinal cord. Unfortunately, the use of MRI may be limited in ventilated patients, who cannot maintain the supine position in spontaneous breathing for the whole duration of the exam (i.e. neuro-muscular patients with diaphragm involvement). The use of MRI-compatible ventilator during MRI could be a solution but they are not universally available. Furthermore, their performances are not up to those of the conventional ones and they are not always compatible with Non Invasive Ventilation (NIV). Findings: This case report describes an easy and low-cost solution to ventilate a patient non-invasively during the MRI procedure. The patient in this case was a 45-yr-old man, wheelchair-dependent and chronically ventilated in NIV with a forced vital capacity in supine position of 370?ml (10% of predicted normal), affected by Arnold-Chiari Syndrome, and in need of a MRI diagnostic control. Conclusion: The technique proposed, that does not affect the MRI images quality, consists in ventilating the patient using a simple nonmetallic Ventilation Bag, operated by a Respiratory Therapist. This has been proven a useful and economical solution for ventilatory support during MRI for a respiratory-dependent patient with Arnold-Chiari Syndrome. 相似文献
3.
《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents. 相似文献
4.
Hend Kothayer Samy M. Ibrahim Moustafa K. Soltan Samar Rezq Shireen S. Mahmoud 《Drug development research》2019,80(3):343-352
In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED50) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b , 4a , 4c , 4f , 4j , and 4i , showed very low ED50 values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABAA binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier.
相似文献
Hit, Lead & Candidate Discovery |
5.
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) in particulate matter that has a diameter of ≤2.5 μm (PM2.5). Studies have demonstrated that BaP exposure causes oocyte meiotic arrest in mice. However, whether BaP exposure also affects oocyte maturation in offspring remains unclear. To test this, female mice were administered BaP before pregnancy to generate BaP-exposed offspring. Our findings showed that BaP exposure reduced the in vitro maturation and increased the abnormalities of meiotic apparatus in offspring oocytes. In addition, BaP exposure reduced the mitochondrial content and intracellular ATP generation, induced early apoptosis, increased reactive oxidative species accumulation and the genomic DNA 5-methylcytosine (5mc) level in offspring oocytes. Along with the abovementioned defective parameters, maternal BaP exposure further compromised the embryo developmental competence of offspring oocytes. In summary, our study demonstrated that maternal BaP exposure compromised offspring oocyte maturation and quality. 相似文献
6.
Synaptic vesicle glycoprotein 2A (SV2A) has been previously characterized as an imaging biomarker for assessment of synaptic density in positron emission tomography (PET) studies of patients with neurological conditions. To provide detailed maps of the brain localization of SV2A autoradiography studies were carried out using the SV2A radioligand [11C]UCB-J and whole hemisphere sections of non-human primate (NHP) and human brain. Binding of [11C]UCB-J was observed in all evaluated grey matter structures of the primate brain, with highest density in the caudate nucleus and cortex and lowest density in pons and globus pallidus. The density of [11C]UCB-J binding sites in human brain showed a good correlation with that in NHP brain. Binding of [11C]UCB-J in the white matter was very low relative to that in grey matter containing structures and was only inhibited to a minor extent by co-incubation with a saturating concentration of unlabelled UCB-J. The high-resolution images obtained in the present study may aid the interpretation of data acquired in human subjects examined using [11C]UCB-J in PET studies. In addition, observation of low binding for [11C]UCB-J in white matter (centrum semiovale) supports that this structure can be used as a reference region for quantitative analysis of [11C]UCB-J PET data. 相似文献
7.
Selena Milicevic Sephton Tunde Miklovicz Joseph J. Russell Aniruddha Doke Lei Li Istvan Boros Franklin I. Aigbirhio 《Journal of labelled compounds & radiopharmaceuticals》2020,63(3):151-158
An automated radiosynthesis of carbon-11 positron emission tomography radiotracer [11C]UCB-J for imaging the synaptic density biomarker synaptic vesicle glycoprotein SV2A was established using Synthra RNPlus synthesizer. Commercially available trifluoroborate UCB-J analogue was used as a radiolabelling precursor, and the desired radiolabelled product was isolated in 11 ± 2% (n = 7) nondecay corrected radiochemical yield and formulated as a 10% EtOH solution in saline with molar activities of 20 to 100 GBq/μmol. The method was based upon the palladium(0)-mediated Suzuki cross-coupling reaction and [11C]CH3I as a radiolabelling synthon. The isolated product was cGMP compliant as demonstrated by the results of quality control analysis. 相似文献
8.
Tessa Timmers Rik Ossenkoppele Denise Visser Hayel Tuncel Emma E Wolters Sander CJ Verfaillie Wiesje M van der Flier Ronald Boellaard Sandeep SV Golla Bart NM van Berckel 《Journal of cerebral blood flow and metabolism》2020,40(12):2464
The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [18F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [18F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr80–100 and SUVr110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods. 相似文献
9.
《Journal of vascular and interventional radiology : JVIR》2020,31(5):795-800
From 2015 to 2019, 9 patients underwent ultrasound-guided intranodal lymphangiography for the treatment of a chyle leak following thoracic outlet decompression surgery. Chyle leaks were identified by Lipiodol (Guerbet, Roissy, France) extravasation near the left supraclavicular surgical bed in all patients. The technical success rate of thoracic duct embolization was 67% (6 of 9), including fluoroscopic transabdominal antegrade access (n = 4) and ultrasound-guided retrograde access in the left neck (n = 2). Clinical success was achieved in 89% of patients (8 of 9). The mean interval from lymphangiography to drain removal was 6.6 days (range, 4–18 d). No patients had a chyle leak recurrence during clinical follow-up (mean, 304 d). 相似文献
10.
史树利 《医药高职教育与现代护理》2020,3(2):221-224
摘要 目的 观察三种不同时机下术前导尿配合手术室护理对全身麻醉(全麻)手术患者苏醒期躁动的影响。方法 选择2017年1月~2018年12月于我院行择期全麻手术的患者100例,根据术前导尿时机分为3组:A组(手术当日清晨在病房导尿,33例)、B组(麻醉前在手术室导尿,30例)、C组(麻醉平稳后在手术室导尿,37例)。记录并比较3组麻醉时间、术中输液量、术中出血量、苏醒时间及导尿前后收缩压(SBP)、舒张压(DBP)及心率(HR)变化,比较3组一次性导尿成功率、术后导尿管适应度及苏醒期躁动发生情况,采用自拟问卷调查患者护理满意度。结果 3组麻醉时间、术中输液量、术中出血量及苏醒时间比较,差异无统计学意义(P>0.05);A组导尿后SBP、DBP、HR较导尿前均显著升高(P<0.05),B组和C组SBP、DBP、HR与导尿前比较,差异无统计学意义(P>0.05);A组一次性导尿成功率显著低于B组和C组,术后导尿管适应度显著差于B组和C组(P<0.05);A组苏醒期躁动发生率显著高于C组,苏醒期躁动分级显著高于C组P<0.05);A组护理满意度评分显著低于B组和C组,差异有统计学意义(P<0.05)。结论 在麻醉前后于手术室进行导尿的效果明显优于手术当日清晨在病房导尿,配合手术室护理干预可有效提高患者术后对导尿管的适应度,降低苏醒期躁动发生率,提高患者护理满意度。 相似文献