药物化学案例研究(英文版)CASE STUDY for 10
Study_on_the_pharmacological_activities_and_chemic
ReviewStudy on the pharmacological activities and chemicalstructures of Viburnum dilatatumZhiheng Gao, Yufei Xi, Man Wang, Xiaoxiao Huang*, Shaojiang Song*Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research &Development, Liaoning Province, School of Traditional Chinese Materia Medica, ShenyangPharmaceutical University, Shenyang 110016, ChinaAbstractViburnum dilatatum (jiami in Chinese), belonging to the Caprifollaceae family, is widely distributed in Japan and China. Phytochemical investigations of Viburnum dilatatum (V. dilatatum) have resulted in the isolation of triterpenoids, phenolic glycosides essential oil, norisoprenoids, etc. Research results have shown that the chemical constituents of V. dilatatum possess various pharmacological activities, including antihyperglycemic, antioxidant activity and antiulcer effects. This study reviewed the chemical constituents and pharmacological activities of V. dilatatum to provide practical and useful information for further research and development of this plant.Keywords: Viburnum dilatatum; pharmacological activity; chemical structures1 IntroductionViburnum dilatatum (called jiami in Chinese, gamazumi in Japanese and snowball tree in English), beloinging to family Caprifoliaceae, is a deciduous low tree distributed widely in the hills of northern China and Japan [1]. There are many types of chemical constituents in Viburnum dilatatum (V. dilatatum), including triterpenoids, * Author to whom correspondence should be addressed. Address:School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Rd., Shenyang 110016, China; Tel.: +86-24-43520793 (Xiaoxiao Huang); +86-24-43520707 (ShaojiangSong);E-mail:*******************(XiaoxiaoHuang); ****************(ShaojiangSong).Received: 2021-04-16 Accepted: 2022-08-28phenolic glycosides and norisoprenoids [2-4]. The leaves have been utilized as a traditional Chinese medicine, and phenolic compounds have been reported as the main active chemical component of the leaves. Many researchers have analyzed the functions of these medicinal components and found that these components have good antioxidant antihyperglycemic and antiulcer effects. For example, the gamazumi crude extract obtained from the squeezed juice of the fruit prevented oxidative injury in rats [5]. This review described the chemical structures and pharmacological activities of V. dilatatum, so as to help readers understand comprehensively the research progress of V. dilatatum and provide help for the development of V. dilatatum.2 Chemical constituents and structuresPrevious reports have indicated that the main chemical constituents of V. dilatatum are phenolic glycosides and triterpenoids.2.1 Phenolic glycosidesThirteen phenolic glycosides were isolated and identified from V. dilatatum by extensive spectroscopic methods, namely p -hydroxyphenyl-6-O -trans-caffeoyl-β-D -glucoside (1) [6], p -hydroxyphenyl-6-O -trans-caffeoyl-β-D -alloside (2) [6], 4-allyl-2-methoxyphenyl-6-O -β-D -apiosyl(1→6)-β-D -glucoside (3) [6], 1-(4’-hydroxy-3’-methoxypheny1)-2-[2’’-hydroxy-4’’-(3’’’-hydroxypropyl)]-1,3-propanediol-l-O -β-D -glucopyranoside (erythro isomer) (4-7) [7], neochlorogenic acid methyl ester (8-9) [7], cryptochlorogenic acid methyl ester (10-11) [7], cyanidin-3-sambubioside (Cy-3-sam) (12) [8], cyanidin-3-glucoside (Cy-3-glc) (13) [8], 5-O -caffeoyl-4-methoxyl quinic acid (4-MeO-5-CQA) (14) [8], chlorogenic acid (5-CQA) (15) [8], quercetin (16) [8], 2-(glucopyranosyloxy)-benzyl-3-(glucopyranosyloxy)-benzoate (17) [9] and jiamizioside E (18) [10]. These structures are shown in Fig. 1.Fig. 1 Phenolic glycosides isolated from V . dilatatumContinued fig. 12.2 TriterpenoidsThere were about seventeen triterpenoids isolated and characterized from V. dilatatum , such as viburnols A (19) [11], viburnols B (20) [11], viburnols C (21) [11], viburnols D (22) [11], viburnols E (23) [11], viburnols F (24) [12], viburnols G (25) [12], viburnols H (26) [12], viburnols I (27) [12], viburnols J (28) [12],viburnols K (29) [12], viburnudienone B 2methyl ester (30) [13], viburnenone H 2 (31) [13],v i b u r n e n o n e B 2 m e t h y l e s t e r (32) [13], viburnudienone B 1 methyl ester (33) [13], viburnenone H 1 (34) [13], and viburnenone B 2 methyl ester (35) [13]. The structures are shown in Fig. 2.Continued fig. 23 Pharmacological activities3.1 Antioxidant activityOxidative stress caused by free radicals and their derivatives leads to disturbances in redox homeostasis. Reactive oxygen species (ROS) are not only endogenously produced during intracellular metabolic processes but also generated by exogenous stimuli such as UV radiation, pollutants, smoke and drugs. The cell triggers its defense systems or undergoes apoptosis when intracellular oxidative status increases. It influences numerous cellular processes including core signaling pathways, which are associated with development of systematic and chronic disorders, such as aging and cancer. Therefore, it is critical to remove cellular oxidants and restore redox balance.solution of V. dilatatum (GSS) had strong antioxidant activity in vivo and prevent stress-induced oxidative damage by the XYZ-dish method and the澳electron spin resonance (ESR) method [14]. The experimental result showed that the concentrations of lipid peroxide in plasma, liver and stomach in the GSS group were reduced. Furthermore, the activities of plasma lactic dehydrogenase, amylase and creatine phosphokinase are ordinarily increased by stress. However, these activities in the GSS group decreased to that in the control group. It was concluded that gastric ulcer formation, increase of lipid peroxidation in plasma and tissues and elevation of plasma enzymatic activities were confirmed in rats with water immersion restraint stress. It was also found that intake of GSS could protect the stomach and other tissues from oxidative damage.Kim et al. identified and isolated two major anthocyanins by NMR and LC-ESI-MS/MS, namely, cyanidin 3-sambubioside (I) and kuromanin (II) [15]. By the electron spin resonance method, the superoxide anion radical scavenging activities of I and II were evaluated with the IC 50 values of 17.3 and 69.6 µM, and their activities on hydroxyl radicals were evaluated with the IC 50 values of 4.3 and 53.2 mM. As the positive control, the IC 50 values of ascorbic acid were 74.2 µM on superoxide anion radicals and 3.0 mM on hydroxyl radicals, respectively. The above results suggested that these anthocyanins with radical scavenging properties might be the key compounds contributing to the antioxidant activity and physiological effects of V . dilatatum fruits.Woo et al. determined the free radical scavenging capacity of VD (the leaves of V. dilatatum ) [16]. Anti-oxidant activity of the extracts was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. Butylated hydroxytoluene (BHT), a synthetic antioxidant, or α-tocopherol, was used as the positive control in these assays. The experimental result showed that VD inducedincrease in radical scavenging activity. In addition, lipid peroxidation inhibitory activity was determined via measurement of MDA (Malondialdehyde) levels using mouse liver tissue homogenate treated with various concentrations of the extracts. The concentration-dependent decrease in MDA levels observed was consistent with radical scavenging activities of the extracts. To examine whether VD extracts could protect mam-malian cells from oxidative stress, cultures of a human mammary gland-derived epithelial cell line MCF-7 were treated with each extract prior to challenging them with tBHP. The intracellular ROS (Reactive oxygen species) production was determined with the relative intensity of dichlorofluorescein fluorescence. While intracellular ROS formation was significantly promoted by tBHP treatment, the augmented ROS level was significantly reduced after the treatment with VD extracts.3.2 Antihyperglycemic effectIwai et al. used an oral glucose tolerance test on the diabetic rats [17]. They found that the elevation of plasma glucose level after oral administration of 2 g/kg glucose was suppressed by the repeated administration of the freeze-dried powder of V. dilatatum fruit juice (CEV). The α-glucosidase inhibitory activities of isolated compounds from CEV were also measured. Cyanidin 3-sambubioside and 5-caffeoyl quinic acid A showed inhibitory activity. These results suggested that V. dilatatum fruit had the antihyperglycemic effects.4 ConclusionV. dilatatum is distributed widely in the hills of northern China and Japan. Currently, the studies on V. dilatatum have been conducted at home and abroad, but few studies focus on its chemical components and pharmacological activities. Previousphytochemical investigations showed that the constituents of V. dilatatum included triterpenoids, phenolic glycosides, norisoprenoids and other compounds. This study describes thirteen phenolic glycosides and seventeen triterpenoids and their different degrees of antihyperglycemic, antioxidant activity and antiulcer effects, aiming to provide a reference for further studies on V. dilatatum and pharmaceutical development.References[1] Jeffrey B, Harborne A. Colour atlas of medicinal plantsof Japan. Phytochemistry, 1981, 20: 1467.[2] Miyazawa M, Hashidume S, Takahashi T, et al. Aromaevaluation of gamazumi (Viburnum dilatatum) by aroma extract dilution analysis and odour activity value.Phytochem Anal, 2012, 23: 208-213.[3] Kurihara T, Kikuchi M. Studies on the constituentsof flowers. IV. On the components of the flower of Viburnum dilatatum Thunb. J Health Sci, 1975, 95: 1098-1102.[4] Machida K, Kikuchi M. Norisoprenoids from Viburnumdilatatum. Phytochemistry, 1996, 41: 1333-1336. [5] Iwai K, Onodera A, Matsue H. Mechanism of preventiveaction of Viburnum dilatatum Thunb (gamazumi) crude extract on oxidative damage in rats subjected to stress. J Sci Food Agric, 2010, 83: 1593-1599.[6] Machida K, Nakano Y, Kikuchi M. Phenolic glycosidesfrom Viburnum dilatatum. Phytochemistry, 1991, 30: 2013-2014.[7] Machida K, Kikuchi M. Phenolic compounds fromViburnum dilatatum. Phytochemistry, 1992, 31: 3654-3656.[8] Kim MY, Iwai K, Matsue H. Phenolic compositions ofViburnum dilatatum Thunb. fruits and their antiradical properties. J Food Compos Anal, 2005, 18: 789-802. [9] Lu D, Yao S. Phenolic glycoside from the roots ofViburnum dilatatum. Nat Prod Commun, 2009, 4: 945-946.[10] Wu B, Zeng X, Zhang Y. New metabolite fromViburnum dilatatum. Nat Prod Commun, 2010, 5: 1097-1098.[11] Machida K, Kikuchi M. Viburnols: Novel triterpenoidswith a rearranged dammarane skeleton from Viburnum dilatatum. Tetrahedron Lett, 1996, 37: 4157-4160. [12] Machida K, Kikuchi M. Viburnols: Six noveltriterpenoids from Viburnum dilatatum. Tetrahedron Lett, 1997, 38: 571-574.[13] Machida K, Kikuchi M. Studies on the Constituents ofViburnum Species. XIX. Six New Triterpenoids from Viburnum dilatatum Thunb. Chem Pharm Bull, 1999, 47: 692-694.[14] Iwai K, Onodera A, Matsue H, et al. Antioxidant activityand inhibitory effect of Gamazumi (Viburnum dilatatum THUNB.) on oxidative damage induced by water immersion restraint stress in rats. Int J. Food Sci Nutr, 2001, 52: 443-451.[15] Kim MY, Iwai K, Onodera A, et al. Identification andAntiradical Properties of Anthocyanins in Fruits of Viburnum dilatatum Thunb. J Agric Food Chem, 2003, 51: 6173-6177.[16] Woo YJ, Lee HJ, Jeong YS, et al. Antioxidant Potentialof Selected Korean Edible Plant Extracts. Bio Med Res Int, 2017, 2017: 1-9.[17] Iwai K, Kim MY, Akio O, et al. Alpha-glucosidaseinhibitory and antihyperglycemic effects of polyphenols in the fruit of Viburnum dilatatum Thunb. J Agric Food Chem, 2006, 54: 4588-4592.。
药物化学实验双语教程(一)
药物化学实验双语教程(一)
药物化学实验双语教程
介绍
•药物化学实验的重要性
•如何进行药物化学实验
实验前准备
•实验器材
•实验药物和试剂的准备
实验步骤
1.步骤一：准备实验用溶液
–选择合适的溶剂
–称取适量药物或试剂
–溶解药物或试剂
2.步骤二：测量药物或试剂的物理性质
–测量药物或试剂的溶解度
–测量药物或试剂的沸点和熔点
3.步骤三：进行化学反应
–添加试剂使发生化学反应
–观察反应过程
–记录反应结果
4.步骤四：测定药物或试剂的质量
–使用天平测量药物或试剂的质量
–计算得到准确的质量数据
实验数据处理
•对实验数据进行统计和分析
•生成实验结果报告
结论
•总结实验目的、步骤和结果
•提出后续实验的建议和改进方向
以上是一份关于”药物化学实验双语”的详细教程，希望对您有所帮助。
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药物化学与药物研发案例
药物化学与药物研发案例药物化学是药物研发中的重要领域，药物设计、合成、性质和治疗作用等都是需要药物化学家进行研究和分析的。
本文将介绍几个药物研发成功的案例，并分析了药物化学在这些案例中的作用。
1. 阿司匹林阿司匹林（Aspirin）是一种非甾体类抗炎药，也是最常用的解热镇痛药之一。
它的历史可以追溯到古代时期，人们发现白柳树皮可以用来缓解疼痛。
药物化学家在分离出白柳树皮中的有效成分后，经过多次合成和改良，最终制得了阿司匹林。
药物化学在阿司匹林的研发过程中起到了关键作用。
药物化学家通过对各种合成路线的研究和比较，最终确定了一种合成方法，这种方法具有高效、成本低、易于控制等优点。
同时，药物化学家还对阿司匹林的物理、化学性质进行了深入研究，增加了阿司匹林的稳定性和药效，使其成为一种安全有效的药物。
2. 头孢菌素头孢菌素（Cephalosporin）是一类广谱抗生素，用于治疗各种感染性疾病。
头孢菌素的研发始于20世纪50年代，经过长期的努力，最终在60年代初取得了成功。
药物化学在头孢菌素的合成过程中发挥了重要作用。
药物化学家从天然的青霉素中提取出杆菌素，经过多次合成、扩大规模生产和改良，最终制得了头孢菌素。
药物化学家还对头孢菌素的结构和化学性质进行了深入研究，不断改进其合成路线和生产工艺，提高了头孢菌素的纯度和效力，使其成为一种重要的抗生素药物。
3. 贝伐单抗贝伐单抗（Bevacizumab）是一种针对血管内皮生长因子的单抗药物，用于治疗多种恶性肿瘤。
它的研发历程中，药物化学起到了重要作用。
贝伐单抗的研发始于20世纪80年代，并历经两个十年的时间。
药物化学家在贝伐单抗的开发过程中，不断改进其制备方法和纯化工艺，提高了药物的质量和效能。
药物化学家还对贝伐单抗的结构进行了深入研究，不断改进其结构，提高了药物的亲和力和生物稳定性，使其成为一种安全有效的肿瘤治疗药物。
结论药物化学在药物研发中起到了重要的作用，它不仅负责药物的设计和合成，还研究药物的结构、性质和疗效等，为制药提供了科学依据。
化学论文英文版
化学论文英文版Jun-Ke Wang, Ying-Xiao Zong, Xi-Cun Wang, Yu-Lai Hu, Guo-Ren Yue.Synthesisof N-benzothiazol-2-yl-amides by Pd-catalyzed C(sp2)-H functionalization[J]. CCL, 2015,26(11): 1376-1380Synthesis of N-benzothiazol-2-yl-amides byPd-catalyzed C(sp2)-H functionalizationJun-Ke Wang a,b,c, Ying-Xiao Zong a,b, Xi-Cun Wang a,b, Yu-Lai Hu a,b,Guo-Ren Yue aa Key Laboratory of Hexi Corridor Resources Utilization of Gansu Universities, College of Chemistry and Chemical Engineering, Hexi University, Zhangye 734000, China;b Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China;c Gansu Engineering Laboratory of Applied Mycology, Hexi University, Zhangye 734000, ChinaReceived 11 May 2015, Received in revised form 29 June 2015, Accepted 1 July 2015,Available online 10 August 2015.E-mail addresses: wangxicun@;huyulai@Abstract: A catalytic synthesis of N-benzothiazol-2-yl-amides from1-acyl-3-(phenyl)thioureas was achieved in the presence of a palladium catalyst through the C(sp2)-H functionalization/C-S bond formation. This synthetic methodology can produce various N-benzothiazol-2-yl-amides in high yields with good functional group tolerance.Key words: Benzothiazole Pd-catalyzed1-Acyl-3-phenylthiourea C-H functionalization L-Proline1. IntroductionThe benzothiazole moiety is an important scaffold due to its widespread occurrence in bioactive natural products,pharmaceuticals, organic optoelectronic materials,and ligands for phosphorescent complexes [1-4]. In particular,substituted Nbenzothiazol- 2-yl-amides are an important class of heterocyclic compounds that exhibit a wide range of biological properties [5-9] such as ubiquitin ligaseinhibition [5],antitumor [6],antirotavirus infections [7],modulating the adenosine receptor [8, 9],and the nuclear hormone receptor [9]. For example,the N-benzothiazol-2- yl-cyclohexanecarboxamide,as a new anticancer drug,was selected as one of the most promising screening hit compounds (Fig. 1) [6]. The acylation reaction from2-aminobenzothiazole,one of the classical methods for the preparation of these molecules [5, 6],is known for the limited diversity of the commercially available starting materials. Furthermore,the preparation of 2-aminobenzothiazole also required the use of the toxic bromine.The past several years have witnessed the great progress in the development of the C-S bond formation promoted by transition metals,which can provide moreefficient,practical,and straightforward approaches to valuable sulfur-containing compounds [10, 11]. However,these methods have been mainly focused on the‘‘traditional’’ cross-coupling reactions of ArX (X = Cl,Br,I,OTf,and B(OH)2) and sulfides [12-39]. To achieve greener and more atomeconomic C-S bond formations,transition metal-catalyzed direct oxidative cross-coupling of C-H bonds and sulfides would be ideal [40-47].In our previous work,we have shown that N-benzothiazol-2-ylamides can be synthesized smoothly by Cu-catalyzed intramolecular cyclization of various substituted 1-acyl-3-(2-bromophenyl) thioureas [48]. This method can provide more diversiform Nbenzothiazol- 2-yl-amides through the carbon-heteroatom formation under relatively mild conditions and avoid the use of the toxic bromine. However,the drawback of this procedure is the limited diversity of the commercially available starting materials due to the use of substituted ortho-haloarylamines. In order to further extend the diversity of N-benzothiazol-2-yl-amides,we have recently demonstrated an efficient intramolecular cyclization of substituted 1-acetyl-3-(2-phenyl)thiourea catalyzed by iron through C-H functionalization [49]. This method can provide more diversiformN-benzothiazol-2-yl-amides under relatively mild conditions. However,the purification of the target compounds is challenging using the column chromatography or recrystallization,since it is inescapable to obtain 1-acetyl-3-phenylurea whose polarity is similar to that of 1-acetyl-3-(2-phenyl)thiourea. Recently,Doi’s group[46] reported a Pd-catalyzed synthesis of 2-substituted benzothiazoles via a C-H Functionalization reaction. Therefore,we envisioned that Pd-catalyzed cyclization of 1-acyl-3-(2-phenyl)- thiourea 1would represent a viable method for the formation and purification of substituted N-benzothiazol-2-yl-amides 2(Scheme 1).2. ExperimentalAll reagents were commercially available and used as supplied. Dimethyl sulfoxide (DMSO) was dried and distilled from calcium hydride. N,N-Dimethylformamide (DMF),toluene,DME and CH3CN were dried prior to use using standard methods. Unless otherwise stated,analytical grade solvents and commercially available reagents were used as received. Thin layer chromatography (TLC) employed glass 0.20 mm silica gel plates. Flash chromatography columns were packed with 200-300 mesh silica gel.All new compounds were characterized by IR,1H NMR,13C NMR and HRMS. The known compounds were characterized by 1H NMR, 13C NMR and HRMS. The IR spectra were run on a Nicolete spectrometer (KBr). The 1H NMR and 13C NMR spectra were recorded on a BRUKER AVANCEIII 400 MHz spectrometer. The chemical shifts (d) were given in parts per million relative to an internal standard tetramethylsilane. High resolution mass spectra (HRMS) were measured with a Waters Micromass GCT instrument and accurate masses were reported for the molecular ion (M+). Melting points were determined on a Perkin-Elmer differential scanning calorimeter and the thermometer was uncorrected.2.1. General procedure for the synthesis of1-acyl-3-arylthioureas [49, 50]To a 25 mL round-bottom flask equipped with a magnetic stirring bar was added acyl chloride (10 mmol),NH4SCN (15 mmol) and CH2Cl2 (20 mL),followed by PEG-400 (0.1 mmol). The mixture was stirred for approximately 3 h at room temperature. Aromatic amine (10 mmol) was added to the mixture and stirred for another 2 h at room temperature. The solvent was removed under reduced pressure to give the resulting residue as a solid,which was washed with water three times,to give the crude product.The analytical samples were obtained by recrystallization from C2H5OH in good yields ([4TD$DIF]88%-98%).2.2. General procedure for the synthesis ofN-benzothiazol-2-ylamides by aPd-catalysed C(sp2)-H functionalization reactionA round-bottom flask equipped with a stirring bar was charged with1-acyl-3-arylthioureas (1 mmol),PdCl2 (10 mol%),CuI (20 mol%),Cs2CO3 (2 equiv.),and L-proline (20 mol%) in 5 mL of DMSO. The mixture was stirred at 100 ℃for the indicated time in Table 2. After cooling to room temperature,the reaction mixture was extracted with ethyl acetate (10 mL × 3). The organic layers were combined,dried over Na2SO4 and concentrated under reduced pressure,and then purified by silica gel chromatography (acetone/petroleum ether = 1:4) to yield the desired product2.N-(4-Ethylbenzo[d]thiazol-2-yl)acetamide (2f): A gray solid (80% yield); mp:264-268 ℃; IR (cm-1): 3169.9,2990.1,2359.9, 1661.1,1550.4; 1H NMR (400MHz,CDCl3): δ 9.42 (s,1H),7.67 (dd, 1H,J = 6.3,2.9 Hz),7.27 (dd,2H,J = 4.4,1.9 Hz),3.04 (q,2H, J = 7.6 Hz),2.28 (s,3H),1.34 (t,3H,J = 7.6 Hz); 13C NMR (100 MHz,CDCl3): δ171.64(s),156.91 (s),146.45 (s),136.81 (s),131.98 (s), 125.25 (s),124.22 (s),118.92 (s),25.36 (s),23.51 (s),14.79 (s); HRMS calcd. for C11H12N2OS [M]+:220.0670; found [5TD$DIF]200.0678.N-(6-Fluorobenzo[d]thiazol-2-yl)acetamide (2 g): A white solid (94% yield); mp:224-231 ℃; IR (cm-1): 3207.8,3071.0,2983.9, 2360.4,1689.2; 1H NMR (400MHz,CDCl3): δ 7.70 (dd,1H,J = 8.9, 4.6 Hz),7.53 (dd,1H,J = 8.0,2.5 Hz),7.19 (td,1H,J = 8.9,2.6 Hz), 2.31 (s,3H); 13C NMR (100 MHz,CDCl3): δ 168.33 (s),160.93 (s), 158.50 (s),121.30 (d,J = 9.1 Hz),114.75 (s),108.09 (s),107.82 (s), 23.46 (s); HRMS calcd. for C9H7FN2OS [M]+: 210.0263; found 210.0256.3. Results and discussionWhile not commercially available,benzothioureas are stable and easilysynthesized [50, 51] from inexpensive starting materials in high yields on a multigram scale. Following Scheme 2,the synthesis of benzothioureas can be achieved in a straightforward manner starting from inexpensive aryl acid chloride and arylamines. Aryl acid chloride was treated with ammonium sulfocyanide in the presence of PEG-400in CH2Cl2,followed by the addition of arylamines,to obtain 1-arylacyl-3-phenylthiourea in good to excellent yields. This intermediate can be used directly without further purifications.In a preliminary experiment,we investigated the intramolecular C-S bond formation of 1-acetyl-3-phenylthiourea utilizing PdCl2 (20%) and a mild base (K2CO3,2 equiv.) in DMSO for 20 h at 100 ℃(Table 1,entry 1). However,the reaction almost failed to take place. Subsequently,we screened several metal salts as cocatalysts, includingAlCl3,CuCl2,Cu(OAc)2,CoCl2,NiCl2,FeCl3,CuI, and CuCl,and found that the addition of CuI considerably enhanced this reaction (Table 1,entries 2-8). However,the desired yield was still not obtained. Surprisingly,when Doi’s condition was used,the yield was still very low (42%) (Table 1,entry 9). Generally,the choice of the ligands is important for the reaction catalyzed by the metal,which prompted us to explore the effect of several bidentate ligands. We carried out the reaction of 1-acetyl-3-phenylthiourea by screening these ligands,such as 1,10-phenanthroline,β-keto esters,β-diketones,andL-proline. (Table 1,entries 10-13),and we were pleased to find that the use of these ligands can notably improve the yield of the product under the same conditions,and that L-proline proved to be the best among an array of ligands tested (Table 1,entry 14). When the amount of CuI and PdCl2 was decreased to 20 mol% and 10mol%,respectively,the catalytic activity was maintained (Table 1,entry 14). Furthermore,we also investigated other bases (Cs2CO3 and K3PO4) (Table 1,entries 15- 16),solvents (DMF,DME,and toluene) (Table 1,entries 17-19) and reaction time (Table 1,entries 20-21). When only CuI was used in this cyclization,no reaction can take place (Table 1,entry 22). Thus, the optimized reaction conditions are as the follows: substrate (1 mmol),PdCl2 (10 mol%),CuI (20 mol%),Cs2CO3 (2 equiv.), L-proline (20 mol%) in DMSO (4 mL) within 8 h at 100 ℃.In response to this encouraging result,we used a range of substituted1-acetyl-3-(phenyl)thioureas to investigate the scope and limitation of this reaction. The corresponding products were obtained in excellent yields (88%-98%). The results obtained under the optimized conditions are listed in Table 2. Initially,the substituents of phenyl were screened. The results demonstrate that little effect of the substituted groups on the benzene ring was observed for this transformation.Furthermore,substituents at different positions of the phenyl ring do not significantly affect the efficiency (Table 2,entries 1-8). It is noteworthy that the halosubstituted benzenes survived leading to halo-substituted products,which can be used for further transformations (Table 2, entries 2,7,8 and 11). In order to make the new Sankyo investigational drugs,the R group was selected as a cyclohexyl to give the corresponding products (Table 2,entries 10-12).Although extensive studies on reaction mechanism have not yet been carried out,the proposed mechanism can be proposed according to the similar palladium-catalyzed processes [51] (Scheme 3). 1-Acetyl-3-(phenyl)thiourea was converted to the thioenolate in the presence of Cs2CO3. Pre-association of the sulphur atom in the thioenolate to Pd(OAc)2 facilitates the orthopalladation process with the concomitant release of chloride ion. The formation of the six-membered palladacycle and the subsequent reductive elimination leads to N-benzothiazol-2-yl-amide and Pd(0). The Pd(0) species are reoxidized to Pd(II) by CuI,thus completing the catalytic cycle.4. ConclusionIn conclusion,we have achieved an efficient intramolecular cyclization of substituted 1-acetyl-3-(2-phenyl) thioureas catalyzed by palladium(II) catalysts through C(sp2)-H functionalization. This method can provide more diversiform N-benzothiazol-2-yl-amides efficiently and quickly in high yields under relatively mild conditions. The combination of the generality with respect to the substrate scope and facile accessibility to the starting materials may generate numerous synthetic possibilities. Further mechanistic analysis of these reactions will be the subject of future work.AcknowledgmentsThis work was supported by the National Natural Science Foundation of China (Nos. 21462016,21262010),Natural Science Foundation of Gansu Province and the Advanced Research Fund of Jinchuan Group Co.,Ltd.References[1] R.S. Keri, M.R. Patil, S.A. Patil, S. Budagumpi, A comprehensive review in currentdevelopments of benzothiazole-based molecules in medicinal chemistry, Eur. J.Med. Chem. 89 (2015) 207-251.[2] A. Rouf, C. Tanyeli, Bioactive thiazole and benzothiazole derivatives, Eur. J. Med.Chem.97 (2015) 911-927.[3] A.G. DiKundar, G.K. Dutta, T.N. Guru Row, S. Patil, Polymorphism inopto-electronic materials with a benzothiazole-fluorene core: a consequence of high conformational flexibility of p-conjugated backbone and alkyl sidechains, Cryst. Growth Des. 11 (2011) 1615-1622.[4] T. Girihar, W. Cho, Y.H. 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化学药物发现的典型案例
化学药物发现的典型案例化学药物发现的典型案例导语：化学药物是现代医学的重要组成部分，它们能够改善人类的健康状况，治疗各种疾病。
但是，化学药物的研发和发现并不是一个简单的过程。
在本文中，我将介绍一些化学药物发现的典型案例，探讨其中的科学原理和技术手段。
一、胰岛素的发现与研发胰岛素是一种能够调节人体血糖水平的激素，对于糖尿病患者来说尤为重要。
胰岛素的发现和研发经历了一个漫长而曲折的道路。
1921年，加拿大科学家弗雷德里克·班廷和查尔斯·贝斯特成功从犬腺提取出胰岛素，并通过临床试验验证了其疗效。
此后，人们开始寻找更高效和可靠的胰岛素制备方法，最终在20世纪60年代成功合成了人工胰岛素。
在胰岛素的发现和研发过程中，化学家们运用了许多先进的技术手段，如色谱法、质谱法和核磁共振等。
这些技术能够帮助化学家们快速准确地分离和鉴定药物中的活性成分，从而促进了胰岛素的研发进程。
合成化学也发挥了重要作用，研究人员能够根据分子结构设计和合成新的胰岛素类似物，以提高胰岛素的稳定性和活性。
尽管胰岛素的研发经历了许多困难和挑战，但正是科学家们的不懈努力和创新思维，使得胰岛素成为当今世界上最重要的化学药物之一。
二、抗生素的发现与研发抗生素是一类能够治疗细菌感染的化学药物，对人类的健康发挥了重要作用。
抗生素的发现和研发是一个具有里程碑意义的过程，它为人类解决了许多严重的感染病症。
英国科学家亚历山大·弗莱明于1928年发现了青霉素，这是世界上第一个广谱抗生素，对革兰氏阳性细菌具有极强的杀菌作用。
随后，人们又陆续发现了许多其他抗生素，如链霉素、四环素和头孢菌素等。
抗生素的发现和研发过程中，化学合成和发酵技术发挥了关键作用。
通过合成或提取自微生物培养物中的天然产物，科学家们获得了许多新的抗生素。
高通量筛选技术也为抗生素的发现提供了重要手段。
研究人员能够快速筛选大量的化合物，寻找具有抗菌活性的化合物，并进一步优化它们的药理性质。
case study范文
case study范文Case Study: The Success Story of Airbnb。
In the past decade, Airbnb has emerged as a disruptive force in the hospitality industry, revolutionizing the way people travel and find accommodations. This case study will delve into the factors that have contributed to Airbnb's success and examine the strategies that have propelled the company to the forefront of the sharing economy.Founded in 2008 by Brian Chesky, Joe Gebbia, and Nathan Blecharczyk, Airbnb started as a simple idea to rent out air mattresses in their San Francisco apartment to travelers attending a local conference. Today, the company boasts millions of listings in over 220 countries and regions, offering a diverse range of accommodations from private rooms to entire homes.One of the key factors behind Airbnb's success is its ability to tap into the growing trend of the sharing economy. By allowing individuals to monetize their underutilized spaces, Airbnb has created a platform that benefits both hosts and guests. This has not only expanded the options for travelers but has also provided a new source of income for hosts, making it a win-win situation for all parties involved.Furthermore, Airbnb's emphasis on creating unique and personalized experiences for guests has set it apart from traditional hospitality providers. The platform allows hosts to showcase their properties in a way that reflects their individual style and personality, offering guests a more authentic and immersive travel experience. This personal touch has resonated with travelers who are increasingly seeking out meaningful connections and local insights during their trips.In addition, Airbnb's innovative use of technology has been instrumental in driving its growth and success. The company has invested heavily in developing a user-friendly platform and mobile app that makes it easy for hosts to list their properties and for guests to find and book accommodations. This seamless and efficient booking process has contributed to Airbnb's popularity and has helped it gain a competitive edge in the market.Another key aspect of Airbnb's success is its focus on building a strong and trusted community. The company has implemented rigorous screening processes and verification procedures to ensure the safety and security of both hosts and guests. This has helped to foster a sense of trust and reliability within the Airbnb community, leading to repeat bookings and positive word-of-mouth referrals.Furthermore, Airbnb has been proactive in adapting to the changing needs and preferences of its users. The company has expanded its offerings to include unique experiences and activities, allowing travelers to immerse themselves in the local culture and community. This diversification has enabled Airbnb to cater to a wider audience and has positioned it as a one-stop platform for all aspects of travel.In conclusion, Airbnb's success can be attributed to a combination of factors, including its ability to tap into the sharing economy, its focus on creating personalized experiences, its innovative use of technology, its emphasis on building a strong community, and its proactive approach to meeting the evolving needs of its users. By staying true to its core values and continuously innovating, Airbnb has solidified its position as a leader in the travel and hospitality industry, setting a precedent for other companies in the sharing economy.。
药物化学与药物研发案例
药物化学与药物研发案例药物化学是研究药物的结构、化学性质、合成方法和药效等方面的科学，对药物的研发有着十分重要的作用。
本文将介绍几个药物化学与药物研发的案例。
第一部分：利用药物化学手段优化药物性质案例一：让药物更安全——利用化学手段改善药物的毒副作用曾经有这样一种抗肿瘤药物，剂量稍有误差就可能出现较严重的心脏损伤，严重者甚至需手术治疗。
然而，科学家们意识到了它的结构上的一个小缺陷——一群杂质分子很容易与它发生化学反应，使其转化为有害的代谢产物，导致心脏中毒。
于是，一支药物化学小组着手研究这个问题，他们设计和合成了几种可靠的抗氧化剂，可捕捉这些有害的代谢产物，使药物的毒性降低。
这种新配方成功地通过了动物和人体试验，并取得了成功的市场应用。
案例二：延长药物作用时间——合成药物的长效剂型某疾病的治疗药物需要频繁注射，给患者带来了很大的不便。
药物化学家通过引入高分子材料，将药物制成微球形状，实现了药物间歇性释放，从而让药效更加持久，减少患者的药物负担。
这种长效剂型药物通过了一系列的测试，并在市场上推广。
第二部分：药物化学在药物研发中的应用案例三：人类基因组计划推进药物研发人类基因组计划的成果为药物研发提供了极大的便利条件。
一种以人脉冲蛋白基因（HPP）编码的蛋白分子被发现与乳腺癌的发展有关，科学家们利用计算机模拟和化学合成手段设计和制备了多个HPP对接点的类似物，筛选得到了具有较高亲和力和选择性的化合物，利用这些化合物可以抑制乳腺癌的发生和发展，成为治疗乳腺癌的重要药物。
案例四：利用药物结构异构构建新型药物钱某是某家制药公司的首席技术官，他发现了一种新型抗肿瘤药物结构，但这个药物的局限性是副作用很严重。
经过一些科学家的研究，他们发现了药物结构的一个异构体，这个异构体对肿瘤的治疗效果和副作用明显优于原药物结构，从而成功地走向了市场。
结论药物化学是药物研发过程中不可缺少的一环，从化学结构的合成、性质的优化，以及药物研发等方面对药物的研究有着重要的作用。
英语论文案例分析-casestudy
英语论文案例分析-Case study英语论文案例分析:Case studyCase1The ChaoZhou Calen Fashion Company Ltd’ is a private midsized firm located in the edding dress ton —Chaozhou China, ith the area of 1500 square meters. Its produces are mainly of varieties of beading, machine embroidery, and movable floers decorated edding dresses and evening dresses. The firm is a private enterprise but registered as a tonship collective enterprise in 1988 due to policy reason. It produced evening and edding dress for a foreign trade firm in Shanghai exporting to the Japan market. The export share of the firm has alays been close to 100 percent due to heavily dependent on OEM, i.e. producing for other firms and brands. Mr. Cai, one of the shareholders of Calen Fashion, joined Calen Fashion in 2006. He has been orked for a large-scale import and export pany for 5 fears mainly engaged in the field of evening dressing .During that time, he accumulated export experience and overseas customers resources. In 2006, he met the factory manager Mr. Wang through orking relationship. After several times contact, Mr.Cai decided to cooperate ith Mr. Wang to run Calen Fashion together. Mr.Cai used his knoledge and experience to obtain theself-export right for Calen Fashion and registered an on brand for domestic market in 2006. From 2016, the firms obtained export rights and started to accept orders also from the US and Canada hich are mostly introduced by Mr. Cai. Japan still accounts for 60 percent of the export, but is decreasing. The full focus of Calen Fashion has been OEM for the international market, thereby having close to 100 % export. In 2006, the pany registered an on brand for the domestic market, hich no accounts for 5 percent of the sales.Case2Skyline Architecture FirmThe Skyline Architecture Firm is a private midsized architecture design firm located in Beijing. The firm as established in 2003, firstly undertaking project design and urban planning for domestic realty panies. According to Chinese construction regulation, foreign architecture pany ho involved in construction project in China should choose a Chinese architecture firm as a coordinator. From the beginning, through business and personal connections, the firm got many opportunities to ork ith foreign design firms in China’s project. In 2006, the firm started the first overseas project in Qatar, cooperated ith Chinese Construction Company to provide the conceptual design for Qatar clients. From then on, skyline architecture firm try to engage in international architecture petition to explore international market. Hoever, the main customer is still in China. In 2016, through an old business partner, ho orks as the project manager in a Vietnam realty pany, skyline architecture firm obtained their second overseas project. Until 2016, the firm’s overseas turnover accountfor 5% of total revenue.Mr. Chen, the intervieee, is a co-founder of the firm. He has been orked for one of the biggest state oned Architecture Design Research Group. The other partner, Mr. Cui, has been orked in Hong Kong for 5years. They set up skyline in 2003 and focused on cater to domestic realty pany. Mr. Chen said most of the ne customers introduced by business netork.Case3The ‘Shunyi Jiahua Ganment Company Ltd’ is a tonship garment process factory located in Beijing. The pany as established in 1998 and is producing apparel of cotton, ool, silk, etc., e.g.leisure shirts. The firm as established in 1998 and until 2001 it as a tonship enterprise attached to Dahua Garment Company Ltd., hich is one of the biggest state oned garment factories in Beijing. Dahua Ganment subcontracted its foreign orders to cooperative process factories, Jiahua Ganment as one of them. In 2001, China abolished the export a system gradually since the entry in the World Trade Organization . Dahua start to lose its advantage because the pany used to get export a as a state oned enterprise from Chinatex Corporation, hich is alarge-scale state-oned group corporation engaging production and trade of ra materials, textiles and garments. Under the circumstances, Jiahua started to seek orders from other trade or agent panies to make up the shortage order from Dahua. In 2006, Jiahua separated from Dahua Garment officially and kept on OEM for the international market. The export share of the firm has alays been to 100 percent by indirect export. Their products mainly for European clothing brand.。
高阶能力导向进阶式研究性学习模式探索与实践——以“药物化学”课程为例
Univ. Chem. 2023, 38 (12), 51–60 51收稿：2023-06-02；录用：2023-06-26；网络发表：2023-07-19*通讯作者，Emails:*********************.cn(郭文婷);****************.cn(赵丽)基金资助：兰州交通大学2022年重点教改项目(JGZ202205，JGZ202203)；2023年兰州交通大学校级课程思政示范课程(1010070957)；2022年兰州交通大学《药物化学》校级一流课程(101025060134)；兰州大学教育教学改革研究项目(202120)；2023甘肃省高等教育教学成果培育项目；2022甘肃省高等教育教学成果培育项目•专题• doi: 10.3866/PKU.DXHX202306007 高阶能力导向进阶式研究性学习模式探索与实践——以“药物化学”课程为例郭文婷1,*，赵丽1,*，汪宝堆2，马妍1，赵仲丽11兰州交通大学化学化工学院，兰州730070 2兰州大学化学化工学院，兰州 730000摘要：针对药物化学课程教学存在的问题，提出高阶能力导向进阶式研究性学习模式的教学创新。
采用P-MASE 研究性学习模型与进阶式教学活动设计相结合，创建以高阶能力为导向的“案例趣研+创研活动+项目挑战”进阶式教学活动，搭建教学场景，融入教学内容。
学生在教师指导下通过P-MASE (即引入问题Problem-寻找方法Method-科学分析Analysis-有效解决Solution-效果评价Evaluation 五个环节)推进药物化学研究性学习，完成理论构建，同时促进提升学生科研能力和创新思维。
通过分析药物化学课程达成度证实，该模式能够有效提高课程高阶性、创新性和挑战度。
关键词：药物化学；高阶能力导向；研究性学习模型；进阶式教学活动中图分类号：G64；O6Exploration and Practice of Higher-Order Competency-Oriented Progressive Research Learning Model: A Case Study of a “Pharmaceutical Chemistry” CourseWenting Guo 1,*, Li Zhao 1,*, Baodui Wang 2, Yan Ma 1, Zhongli Zhao 11 School of Chemistry and Chemical Engineering, Lanzhou Jiaotong University, Lanzhou 730070, China.2 School of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.Abstract: In response to the issues in the teaching of the medicinal chemistry course, we propose an innovative teaching approach based on a higher-order skills-oriented advanced research-oriented learning model. By combining the P-MASE research-oriented learning model with advanced instructional activity design, we create a higher-order skills-oriented teaching activity that integrates “interesting case research + creative research activities + project challenges”, and construct a teaching scenario that incorporates the instructional content. Under the guidance of teachers, students advance their research-oriented learning in medicinal chemistry through the P-MASE framework, which involves problem identification, method exploration, scientific analysis, effective solution, and evaluation of outcomes. This approach facilitates theoretical development and enhances students’ research and innovation thinking skills. Through an analysis of the achievement of the medicinal chemistry course, it is confirmed that this model can effectively enhance the higher-order nature, innovation, and challenge of the course.Key Words: Medicinal chemistry; Higher-order competence orientation; Research-oriented learning model;Activities of progressive teaching52 大 学 化 学 Vol. 38 1 引言新时期我国高等教育全面推进“四新”建设，以提高人才培养质量。
药物化学—英文
The unexplored potential of microbial diversity
Extremophilic microbes abound in extreme habitats
alkalophiles, alkaline,piezo(baro) and thermophiles and psychrophiles. These extrem enviroments will yield novel bioactive chemotypes.
“A small collection of smart compounds may be more valuable than a much larger hodgepodge collection mindlessly assembled”-- stated by Danishefsky in 2002.
Fig. Enzymatic processes operative in cell cycle progression
New screening methods
In early days, even the use of simple broad-based bioactivity screens resulted in the isolation of many bioactive compounds; A large number of robust and specific biochemical and genetics-based screens permit the detection of bioactive compounds in natural product extracts with great precision. High throughput screening (upward of 50.000 assay points per day in a number of cases)
做新药研发管理你大概会觉得有用的几本入门书
做新药研发管理你大概会觉得有用的几本入门书药物的整个开发途径大约需要8-15年左右，这一段时间可以大致分成几个阶段，每个阶段的研究内容、所需知识都不尽相同。
如果对每一个阶段都希望进行管理，那么至少应当理解这些工作的意义和价值，管理的基础是至少部分地了解事物的本质，所以对于医药研发人员来说，需要一些必备的常识。
今天我们将首先划分药物研发的阶段，粗浅地讨论一下每一阶段所必备的知识，主要介绍一下获得这些知识的最快途径。
希望这些内容对于即将开始药物研发的新人能够提供一些帮助，尽量避免一些浪费时间的著作。
临床阶段部分可能要到下次再做分享。
红色字体强烈推荐。
药物研发的第一个主要阶段是化合物的发现与早期开发阶段。
这一阶段的主要目的是找出可能有效安全而且成药性较好的药物，药物化学家和生物学研究员是这一阶段的主要两类工作人员，工作的中心是药物化学家的药物分子设计。
本次推送的这一部分主要内容有两个：药物化学案例学习和生物学基础。
药物化学的案例学习药物化学在过去的30年内，受到法规环境、技术进步等多方面的影响，在药物设计上的进步可谓日新月异。
技术迭代在未完成产品开发就已经完成，使得技术进步未能见证产品优势。
药物化学家的工具也变得越来多丰富，无法判断一些药物的设计方法能否禁得住考验。
药物设计工具未经验证，药物化学团队需要一些案例指导。
在之前的推送里，我分享了药物化学的入门书籍，感兴趣的读者可以回翻到当期。
这类书的质量往往主要来源于药物发现团队是否讲述了足够多的内容，就是一般所谓的“干货”，另外选题与选材也比较重要。
由于缺少强有力的编辑团队，这类书的文笔参差不齐，推荐其中的《Accounts in Drug Discovery: Case Studies in Medicinal Chemistry》，与《Casestudies in modern drug discovery and development》。
国内去年的《明星药物》也可以读一读，但对于药物开发缺少实质帮助。
英汉对照药物化学介绍
Medicinal or pharmaceutical chemistry is a discipline at the intersection of chemistry and pharmacology, and involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. The content of medicinal chemistry also includes the study of existing drugs, their chemical structure, physical and chemical properties, chemical stability, biological properties, structure-activity relationships (SAR), metabolism, chemical mechanism of interaction between drugs and biological targets, etc.药物化学是化学和药理学之间的交叉学科，其内容涉及适合于治疗用途的新化学单体药物的鉴定、化学合成和开发利用。
药物化学的内容还包括对现有药物的化学结构、理化性质、化学稳定性、生物活性特征、构效关系（SAR）、体内代谢以及药物与其生物靶点相互作用的化学机制的研究等。
Medicinal chemistry is a discipline mainly concerned to new drug research. Early advances in medicinal chemistry were concerned principally with the estimation, isolation, structural determination, and synthesis of medicinal agents of natural origin. A second major area was the synthesis of simplified fragments of complex drug molecules. Recent medicinal chemistry obtained a great progress by the explosive development of molecular biology, physical chemistry, organic chemistry, high-speed computer and new, powerful analytic methods including various types of chromatography, radioimmunoassay, mass spectrometry, X-ray crystallography, and nuclear magnetic resonance spectroscopy, etc.药物化学是与新药研究有关的一门学科。
药物化学与药物研发案例
药物化学与药物研发案例近年来，药学发展及研发业务扩大了药物化学的重要性，有效的药物化学设计已经成为研发活动的关键要素之一。
药物化学的作用是改变药物的性质，优化现有药物，以实现有效的治疗。
它可以使药物和有毒物质进行混合以提高其有效性，也可以应用到修饰药物以改变其物理和化学属性，以改善过渡和药物分布。
本文将以研发公司Evisan Pharmaceuticals（以下简称“Evisan”）为背景，讨论其在药物化学领域的应用。
Evisan是一家专门从事药物研发的全球化制药公司，利用多学科知识和跨学科知识进行药物开发。
它的研发项目主要集中在药物开发，药物化学，药物分析，药物毒理学，药理学和其他相关领域。
Evisan以其多学科的实验室研发能力广泛应用药物化学。
作为药物开发的关键组成部分，它采用定性和定量分析方法来开发新的药物结构。
不仅可以用于合成新的药物或优化已有的药物，还可以应用于改进药品的分子结构以及合成新型抗菌剂。
该公司研发的药物结构优化方法已经被广泛用于设计和研发单细胞和分子药物，以及新型抗感染药物和改善现有药物的功效。
例如，Evisan的研究人员正在开发一种新型的抗结核药物，它的药物结构被优化，使其更容易通过血液到达结核病毒感染的细胞。
为此，研发团队先收集了结核病毒相关的生物信息，然后利用药物化学筛选出一组化学结构，优化其药物特性，以提高药效和安全性。
最后，研发团队运用分子对接和计算机模拟技术，模拟药物与靶结构之间的相互作用，从而确定最佳药物结构。
最终，该公司将这种新型抗结核药物投入临床试验，以开发一种有效的抗病毒疗法。
药物化学在药物研发过程中发挥着重要作用，其主要功能是修饰药物结构，改善药物性质，开发新药，监测药物研发过程，以及优化药物结构以提高药物安全性、有效性和经济性。
Evisan研发的药物化学的应用是一个很好的实例，它的研发团队利用药物化学的多学科知识和跨学科知识，开发出新型的抗病毒药物，以应对传染性疾病的威胁。
药物化学与药物研发案例
药物化学与药物研发案例
药物化学是药物研发的基础，涉及到药物的结构和性质。
它涵盖了从发现到研发、开发和应用新药物的全流程。
这是一个系统工程，在不断进行中，药物研发和药物化学也在发展壮大。
药物研发涉及到多个阶段。
首先，化学家需要利用合成化学原理，通过试验，构建新药物。
在这个阶段，化学家需要分析新药物的结构和性质，确定其有效性和安全性。
其次，新药物要经过临床试验，以确定其有效性和安全性。
临床试验的内容包括临床研究，它需要在不同的人群中记录药物的疗效和副作用，以及药物的分布、消除和代谢等，以加深对新药物的了解。
然后，新药研发必须经过严格的审批程序，以确保药物质量。
一旦审批通过，新药就可以上市，被广泛应用。
最后，新药安全性应经常检查和评估，以验证药物的质量和效果，以确保病人的安全用药。
以上就是药物化学与药物研发的一个简单案例。
药物化学是一个复杂的过程，从发现新药物到它的研发、开发和应用，都需要多方面的知识和技术支持，以及严格的临床观察和审批程序。
未来，药物化学和药物研发将会进一步发展，给人们带来更多的新药物，从而改善人们的健康状况。
药物化学和药物研发的进步对于人类的健康和福祉至关重要，因此，未来药物化学和药物研发仍将是全球各国最重要的研究课题之一。
希望未来的研究将能够为人们带来更多的新药，有效改善疾病的症状，
为人类的健康福祉贡献力量。
“网络课程学习+课堂授课+临床用药案例讨论”三维立体的临床药学专业《药物化学》教学模式研究
-药学教育-“网络课程学习+课堂授课+临床用药案例讨论”三维立体的临床药学专业《药物化学》教学模式研究徐晓莉，向华，江程(中国药科大学药学院，江苏南京211198)摘要：随着临床精准用药的需求加大，传统的药物化学教学模式越来越难以满足临床药学专业学生的学习需要。
本文从《药物化学》课程特点出发，立足于社会实际需要，结合互联网+技术，构建线上线下混合式教学方法，同时匹配临床用药案例分析，形成了三维立体的临床药学专业《药物化学》教学新模式，提高了该课程的教学质量，为医药学院精准药学专业人才的培养提供了新策略。
关键词：药物化学；临床药学；临床用药；教学模式中图分类号：G642文献标识码:A文章编号：2095-5375(2021)05-0344-003doi：10.13506/ki.jpr.2021.05.014Online course+classroom learning+clinical case study:three-dimensional teachingmode of medicinal chemistry in clinical pharmacyXt XiaoZi,X/ANG Hua,J/ANG Cheng(School of Pharmacy,China Pharmaceutical tni^ersity,Nan/ing277795,China)Abstract:To meet the demand of clinical precision medicine,the traditional teaching mode of medicinal chemistry is more and more difficult to meet the learning objectives from clinical pharmacy students.Based on the characteristics of medicinal chemistry course,we build a three-dimensional teaching mode for clinical pharmacy by combining the online courses,classroom learning and the clinical case study.The novel teaching mode improves the teaching quality and provides a solid foundation for precision pharmacy.Key words：Medicinal chemistry;Clinical pharmacy;Clinical medication;Teaching model我国于2015年启动中国精准医疗计划，为中国现代医疗带来了一场变革,精准药学是精准医学的一个非常重要的分支。
生物正交的药物化学
生物正交的药物化学（中英文实用版）Title: Bioorthogonal Drug ChemistryTitle: 生物正交的药物化学In the field of medicinal chemistry, bioorthogonal reactions have gained significant attention in recent years.These reactions are unique because they occur exclusively in living cells, without interfering with the biological environment.This characteristic makes them particularly useful for targeted drug delivery and imaging techniques.生物正交反应在药物化学领域近年来备受关注。
这些反应之所以独特，是因为它们仅在活细胞中发生，而不会干扰生物环境。
这一特点使它们在靶向药物递送和成像技术中特别有用。
One of the most well-known bioorthogonal reactions is the click reaction, which involves the formation of a cycloaddition between an azide and an alkyne.This reaction is highly specific and efficient, and it has been widely applied in the creation of drug-delivery systems and fluorescent probes.最著名的生物正交反应之一是点击反应，它涉及叠氮化物和炔烃之间的环加成。
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CASE STUDYMedicinal ChemistryCase 1A dentist calls your pharmacy and asks you prepare an antiseptic mouthwash for a patient with a painful bacterial infection of the oral cavity. You ask your second-year pharmacy intern to research the project, and she suggests combining bupivacaine hydrochloride (local anesthetic) with cetylpyridinium bromide(antiinfective)Case 1-Q1 Identify the acidic, basic, or neutral character of the two drug molecules in the case based on salt name.Case 1-Q2 Are these species ionized or unionized in salt form?Case 1-Q3 From an acid-base standpoint, is the mouthwash suggestion sound?Case 3A distraught mother calls the poison control center where you work. Her 6-year-old son just are half a bottle of NH4Cl tablets meant for the family cat. As a complication of morbid obesity, He is hypertensive (the son not the cat), and has been on timolol maleate (blockadren) for 6 months. A significant fraction of timolol is excreted unchanged in the urine, and an overdose can result in bradycardia and hypotension.Case 3-1Q From an acid-base standpoint, is this a potential medical emergency? Why, or whynot?Case 5ZT, a 26-year-old single mother of four with a history of depression, is rushed unconscious to the emergency room of the hospital where you work. The attendant hands you an empty bottle that had contained 10 tablets of amobarbital sodium (pKa = 8.0) After stabilizing respiration and performing gastric lavage, you decide to enhance the renal elimination of the drug .ZT has a urinary pH of 6.0.H NNOOONa pKa = 8.0Case 5 –Q1 What is the acid-base character of amobarbital sodium?Case 5 –Q2 What would be the ratio of ionized to unionized drug forms in this patient ’s urine?Case 5 –Q3Would you recommend the IV administration of NH4Cl or NaHCO3?Case 5 –Q4The ER nurse is preparing to add phentermine hydrochloride to the IV bag containing the pH modifier you have just elected. Would you stop him? Why, or why not?, HClONHCase 17You are an M.D./Ph.D. (in medicinal chemistry, of course) practicing general medicine in the early 1930s. The medical community is all atwitter about a new anti-infective, sodium sulfanilamide, which has shown value in the treatment of urinary tract infections and infection secondary to burns. You are concerned, however, about the tendency of this agent to cause crystalluria, which can result in severe, life-threatening kidney damage. The pKa of sulfanilamide (17.1) is 10.4.Case 17-Q1 Draw the structure of Sodium Sulfanilamide .Case 17-Q2Why would a patient with a urinary pH of 5.4 be at greater risk for the development of crystalluria than one with a urinary pH of 6.4? What would be the ratio of ionized to unionized sulfanilamide drug forms at each urinary pH?Case 17-Q3 Which urinary pH modifier would you prescribe for a patient who began to show symptoms of crystalluria, NH4Cl or NaHCO3?Case 17-Q4 As a medicinal chemist, you understand the impact of structure on the therapeutic profile of drug molecules, and drug design visions are now dancing in your head. Which of the three modified sulfanilamide structures (17.3~17.5) would have a higher therapeutic index with regard to crystalluria? What is the structural basis for your answer?17.1SNH2H2N O OH17.3SNH2NO ONNH17.4SNH2N O O OH17.5SNH2NO OCase 28LP, a prepharmacy student attending a local junior college, has been taking organic chemistry (her favorite class) and has been starting to really understand organic structures. She has been seeing her physician regularly for allergy problems that are particularly troublesome in the fall (ragweed season ). She has been taking diphenhydramine (28.1) for more than a year now, but it is really bothered by the dry mouth and sleepiness that she has come to associate with takingthis drug. Lately, she has been drinking lots of colas to stay awake in organic chemistry and combat the dry mouth. She now thinks that she is dependent on caffeine. You are the pharmacist on duty at the drug store when LP ’s physician calls to ask for advice regarding an alternative medication.Case 28-Q1 Explain the reasons for the side effects that have been observed with diphenhydramine(28.1).O NCH 3CH 328.1Case 28-Q2 Recommend one of the following drugs as an appropriate choice for this patient. Justify your choice and discuss briefly why the other choices are inappropriate. 28.2 Ranitidine28.3 chlorpheniramine 28.4 cetirizine 28.5 Bethanechol28.2OS NHNH 2NO 2NCH 3CH 3NNCH 3CH 3Cl28.3NNCH 3CH 3Cl28.3ClH NNOOOH . 2HCl28.428.5H 3C N O NH 2H 3CCH 3CH 3OCase 46Imagine yourself as drug information specialist at a poison control center. A technician from the coroner ’s office is investigating a case and requires assistance in identifying the possible sources of benzodiazepines (BZDs) in the toxicology profile of a particular corpse. The technician has identified four distinct BZDs in the blood sample. She believes that the major component is diazepam (46.1) (72% of the identified BZDs) and that the remaining three compounds are metabolites (NOTE: the assay identifies only active compounds).Case 46 –Q1What are the three structures of potential ACTIVE metabolites for diazepam (46.1)?Case 50SA is a 20-year-old university coed who presents to the student health service complaining of extreme nervousness, irritability, and difficulty concentrating. For the past year, SA has constantly worried about achieving sufficiently high grades in her prepharmacy courses to qualify for entry into the Doctor of pharmacy program. She is also concerned about her skin condition, which has worsened since she entered the university 2 years age’s has suffered from atomic dermatitis since high school, a condition which until recently had been kept under control using topical hydrocortisone (0.5% cream). As the time for her interview with the College of Pharmacy admissions committee approaches, SA’s worry increase, and she has become increasingly agitated, is unable to concentrate on her studies, and has shortness of breath and palpitations . To make matters worse, the itching rash on her face and arms has worsened.The student health physician, in consultation with SA’s family doctor, decides on a diagnosis of generalized anxiety disorder (GAD). The two physicians agree that a benzodiazepine is indicated.Case 50-Q1 Select a benzodiazepine from the structures (50.1-50.5) provided that would be the most appropriate for treating SA’s anxiety. Justify your choice on the basis of structure/potency and duration of action/relationships. Eliminate inappropriate choices on the same basis.Case 50-Q2How long should SA maintained on anti-anxiety medication? Explain fully.Case 50-Q3What are you going to do for the patient’s atopic dermatitis?Case 83FP is a 62-year-old male vintner with hypertension that is not well controlled on hydrochlorothiazide 50 mg daily and captopril 50 mg tid. Blood pressures on treatment ranges from 160 to 170 systolic and 95 to 105 diastolic. Ten days ago, FP developed a cold that initially got somewhat better, but the worsened over the last 3 days, with the development of facial pain below the eyes, which is made worse when he bends over; a purulent nasal dis charge that “tastes and smells foul”; and a fever of 101 F. The doctor plans to treat the sinusitis with amoxicillin 500mg tid for 3 weeks and wants decongestant treatment for the first 3 to 5 days, but is concerned about its effect on FP’s blood pressure.FP used Dristan nasal spray for his cold, but stopped because “it made me jittery”. The doctor calls asking for a recommendation for a decongestant that will exert minimal effect on blood pressure and won’t make FP feel jittery.Case 83-Q1 Select a decongestant from the structures (83.1~83.5) provided that you would recommend for FP. Explain your rational on a structure/activity basis.83.1N NClNH OH83.2NH2 OH83.3NNHHO83.483.5NHOHHOCase 84As the inpatient pharmacist at Bigshots University Hospital, you have received a call from a medical student for some drug information. This medical student is working on a case presentation for a patient who has been ordered Aldomet 500 mg IV q6h. His question for you is:why would an IV solution be prepared with α-methyldopate hydrochloride (Aldomet IV [84.1]) rather than α-methyldopate (Aldomet [84.2])?Case 84- Q1 Why would an IV solution be prepared with α-methyldopate hydrochloride (Aldomet IV [84.1]) rather than α-methyldopate (Aldomet [84.2])84.1.HClNH 2HOHO O O 84.2NH 2HOHO OH OCase 86HS, a western Nebraska farmer, is brought by his wife to the emergency room of your local hospital with a broken leg. His also complaining of weakness and dizziness, which he is attributing to the pain of his break. You also note that he is salivating and sweating excessively, has a low heart rate, and is breathing with some difficulty. You discover that, in the farm accident which caused the broken leg, he came in contact with large quantities of the insecticide Parathion(硝苯硫磷酯)(86.1).86.1O 2NOP CH 3O CH 3SCase 86-Q1 Explain the cause of the farmer’s symptoms.Case 86-Q2 Which of structures (86.2~86.5) should be immediately administered? Why?86.2+CH 3H O OH86.3Cl -+N 3NOH86.4Cl -+H 2NON CH 3O CH 386.5Br-+O NCH 3OCH 3N CH 3CH 3Case 88LN is a 74-year-old woman who presents to her HMO with malaise, shortness of breath, and fatigue. She also complains of weight gain and swollen hands and feet. LN has a 6-month history of congestive heart failure (CHF), a 3-year history of hypercholesterolemia, and a 6-year history of adult onset (type II) diabetes mellitus. Two weeks ago, LN suffered a mild stroke and washospitalized for 3 days. She was then discharged with a prescription for oral warfarin (5 mg daily ) for 3 weeks. Her other current medications include: digoxin (0.125mg daily), lovastatin (20mg at night), and tolazamide (250mg daily). The patient’s creatinine clearance is 35 mL/min. The cardiologist determines that the digoxin alone is insufficient to control LN’s congestive heart failure. Because previous attempts to use angiotensin-converting enzyme inhibitors caused intolerable hypotension, it is decided to employ diuretic therapy.Case 88-Q1 Which diuretic(s), of the structures (88.1~88.6) shown, would provide the most benefit? Justify your choice(s).Case 88-Q2 Indicate agents that would be inappropriate and/or less effective than your first choice. Explain why.88.1N OCl H 2NO 2SOHH H N S Cl H 2NO 2SO OCl88.2N N N N H 2NNH 2NH 288.3Cl OClOOH 88.4H NNCl H 2NO 2SO 88.5H OHN OH 2NO 2S88.6Case 90AG , is a 56-year-old construction worker with a 15-year history of hypertension and ischemic heart disease that was well controlled until 6 months ago, when he began having anginal chest pain with increasing frequency and severity. Over the past 2 months, has been seen twice in the ER with chest pain unrelieved by sublingual nitroglycerin. On a third occasion, he was hospitalized with the same symptoms and was given a complete workup. He has severe two vessel disease ,but refuses angioplasty or bypass surgery at this time. His current medications include nifedipine XL, captopril, nitroglycerin ,diltiazem, and aspirin .During the past week, he experienced several anginal attacks each day that were relieved by nitroglycerin; finally, AG has decided to seek more definitive treatment. Tonight he presents to the ER with chest pain unrelieved by nitroglycerin and is sent to the critical care until with the diagnosis of unstable angina pectoris. The attending physician orders IV nitroglycerin and wants to start an IV β-adrenergic blocker to counteract any tachycardia ,but is concerned about its long-term effects on overall cardiac function.Case 90-Q1 Select the most appropriate β-adrenergic antagonist from the structures (90.1~90.6) provided. Justify your choice on the basis of the pharmacology and the comparative pharmacokinetics of the available structures.Case 90-Q2 one of the structures is contraindicated in the patient. Which one is it, and why is it contraindicated?90.1HHN OOHN90.2NOHHOHONOH90.3HONOH O90.4HONOH OO90.5H90.6ONOH HCase 100RV , a student from the local community college,is standing in the OTC section of your pharmacy looking miserable and reading the backs of three product packages. He is trying to select something that will help him get over the cold of the century, and expresses anxiety about being ill with autumn midterm examinations coming up in a few days. Normally quite healthy, he appears very congested and feels “achy ”, but his lungs are still clear. He is taking Nodoz prn (which contains caffeine) to help him stay up nights to study, and admits to no allergies. The products he has pulled off the shelf contain the following chemical compounds.100.1+OH O -O HCH 3N ClCH 3 Cl -+CH 3NH 2OHCH 3100.2 Cl -+NH 3CH 3100.3Case 100 –Q1 What pharmacologic class of the molecule dose RV require? Which of the structures provided (100.1~100.3) fall into this pharmacologic class?Case 100 –Q2 Of the agents (100.1~100.3), which would you recommend? How dose the chemistry of your agent of choice support your recommendation?Case 114Dr.Iris Brown,an ophthalmologist, is seeing a patient with corneal inflammation .She wishes to initiate topical antimuscarinic therapy ,and is considering the merits of the compounds shown (114.1~114.5). Dr. Brown wishes to formulate a potent antimuscarinic in a standard lanolin-based ointment and asks your advice on which product to choose.Case 114-Q1 What chemical property would be most important in a drug molecule destined for a lanolin-based ointment base?Case 114-Q2 What structural features contribute to high antimuscarinic potency in Solanaceous alkaloid molecules?Case 114-Q3 Which of the five contemplated structures(114.1~114.5) would you recommend to Dr. Brown?Case 114-Q4 If Dr. Brown ’s patient returned to her clinic after a number of days on your drug of the choice complaining of dry mouth and blurred vision, how might this be explained?Case 114-Q5 Which of the original five molecules (114.1~114.5) would you have selected if Dr. Brown had wanted to prepare an ophthalmic solution for her patient? Could you have easily modified the structure of the drug you selected for an ointment formulation to make it appropriate for delivery in aqueous solution?Case 143GT is a 12-year-old African-American male who presents to the emergency room with server pain and tenderness in the left lower leg. He also complains of pain in the left knee, but states that the leg hurts more. His leg pain has become progressively worse during the past week. GT has a history of sickle cell anemia and has been admitted to the hospital in the past for supportive treatment and management of sikle cell crisis. GT remembers that he fell on the playground while playing basketball 2 weeks ago. He thought the pain he had been experiencing was due to his disease. The acetaminophen that he had been taking helped to relieve his pain initially, but it dose not appear to be effective now. Blood cultures grew Salmonella typhimurium . Antibiotic sensitivity results will be available in 24 hours. An x-ray of the left tibia was suggestive of osteonecrosis at that site.Case 143-Q1 Select an appropriate penicillin derivative (143.1~143.6) to treat GT’s osteomyelitis along with the preferred route of administration and chemical form. Justify your choice on the comparative microbiologic properties of the chosen agent vs the remaining drugs.CH 3O CH 3CH3114.13OOH114.3CH 3O OH114.4CH 3OOH114.2CH 3OOHH 3C 114.5+143.1H N OSO143.2H ONSO143.2H ON S O143.1H N OSO143.5H NOSO NH 3+143.6H NOSOCOOH+SCase 143-Q2 Assure that sensitivity tests later reveal that your initial choice is ineffective. Explain how this could happen. Would this mean that no penicillin derivative, under any circumstances, would be effective in this case? Explain.Case 143-Q3 Suggest other antibiotics or chemotherapeutic agents that could be employed if the patient were allergic to penicillin.Case 148JD is a 27-year-old prostitute who is admitted to the hospital with fever and severe abdominal pain. She has experienced generalized pain for the past 3 days and has lost her appetite. In addition to the pain in the lower abdomen, JD reports a brown, foul-smelling vaginal discharge. JD reveals that she has been a prostitute for the past 8 years and has been treated on three different occasions in the past 18 months for sexually transmitted diseases: twice for gonorrhea and once for syphilis.Laboratory results show gram-negative cocci, and tests for Cblamydia are pending. A diagnosis of pelvic inflammatory disease (PID) is made, and the doctor decides to administer ceftriaxone (148.7)(250mg IM) to JD and release her with a prescription for an oral tetracycline derivative.Case 148-Q1 What are the most likely causative microorganisms of JD’s PID based on the available information?Case 148-Q2 Why is ceftriaxone specifically employed in this case? Case 148-Q3 What is the purpose of the oral tetracycline derivativ e?Case 148-Q4 Select the most appropriate tetracycline from the structures (148.1~148.6) provided. Justify your choice on the basis of the pharmacokinetic properties of the various tetracyclines available.148.12148.22148.32148.4OHOOH OH O OH NNH 2OOHOHOOH OH O OH NNH 2OOH148.5OH OOH OH O OH NNH 2ON148.6148.7S N N N O OHONHO NSNH 2NCase 149You, as a staff pharmacist at the V A hospital, are called in to consult on a case involving a 55-year-old municipal bus driver, who has been admitted with an acute urinary tract infection. Past medical history includes rheumatic fever with eventual mitral valve replacement and a history of UTIs due to a congenital inflammation of the urinary tract that is not surgically correctable. Blood and urine cultures confirm group D streptococcus (enterococcus). Because of t he microorganism’s inherent resistance to single drug treatment and the potential for subacute endocarditis, a combination of penicillin with an aminoglycoside is indicated. Five years ago, the patient experienced a gentamicin-included elevation in serum creatinine while being treated for a urinary tract infection. Current serum creatnine level is 1.3, with a creatnine clearance of 75mL/min.Case 149-Q1 Why is combination of antibiotics indicated for this patient? Explain the basis of the mechanism(s) of action of the antibiotics.Case 149-Q2 What are the causes for the physician’s concern? Are these concerns justified? Case 149-Q3 Select an aminoglycoside from the structures provided; streptomycin (149.1), kanamycin (149.2), gentamicin (149.3), amikacin (149.5), netilmicin (149.6), tobramycin (149.4), that when combined with penicillin G , would maximize the benefit to the patient and minimize the risks.Case 149-Q4 Provide a rationale for your choice based on the properties of the aminoglycoside chosen and explain why each of the remaining aminoglycoside was rejected.Case 149-Q5 Will dose adjustment(s) of the two antibiotics be required? Explain.O O OCHO HO CH 3OOH OH NHCH 3HO OH OHOHNHCNH 2NHH 2NCNHNH 149.1149.2OOH OH HO NH 2O OHO H 2NOHHONH 2H 2nOHO149.3OH 2NNH 2O CH 3OCH 3CH 3NHOH HOOHNH 2H 2NOH O149.4OCH 2OHOHOH OHONH 2H 2NNH 2HONH 2O。