Globally, cardio-cerebrovascular diseases caused by platelet aggregation pose a grave threat to human health, and hence, research on anti-platelet aggregation is of paramount importance. It has been demonstrated that purine derivatives are essential molecules for antiplatelet aggregation activity. Therefore, it would be of great value to investigate the correlation between the structure of purine derivatives and the antiplatelet aggregation function, which could be of great assistance in the search for novel drugs. In this paper, we investigate the structural modification of molecules with purine structure as backbone, 46 designed 6-alkylamino-alkylthio(alkoxy) purine derivatives were synthesized via a modification procedure and evaluate their antiplatelet aggregation activity, these compounds were analyzed by 3D-QSAR based on self-organized field analysis (SOMFA). The model with significant results was obtained (SOMFA r 2 = 0.855, r 2 cv = 0.843, F = 247.316, SEE = 0.334), and the prediction ability of the model was verified by the test set. The results indicated that judicious modification of substituents would be beneficial in the development of more effective antiplatelet drugs.

MOOCs offer solutions to traditional constraints faced in chemistry experimental teaching,such as limited lab space,insufficient equipment,and rigid scheduling,However,challenges like underutilization,reluctance from students,and faculty unfamiliarity can undermine these efforts.To address these issues,the National Demonstration Center for Experimental Chemistry and Chemical Engineering Education(Beijing University of Chemical Technology)has explored how to effectively use MOOCs to enhance teaching quality.The team has established an extensive array of online experimental teaching resources,implemented a synergistic blended learning model,and developed both a faculty skill enhancement program and a comprehensive system for tracking and feedback on teaching quality.These initiatives have significantly improved educational effects.

Aims In this research, 3D-QSAR evaluation on a set of fresh purinoid compounds that we produced was conducted. This analysis aims to illustrate the correlation between the structure of purine and its ability to prevent platelet aggregation. Our findings could pave the way to discovering novel antithrombotic medications.Background The incidence of cardiovascular disease triggered by the clumping of platelets poses a significant danger to human health. Purine derivatives are important molecules with antiplatelet aggregation activity.Objective The objectives of this research are to establish the correlation between the structure of purine and its ability to prevent platelet aggregation. Such a correlation could aid in the development of innovative antithrombotic medications.Methods In this study, 3D-QSAR investigation on a collection of 75 new purine derivatives, which we synthesized, was conducted, utilizing Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA).Results Significant correlation coefficients (CoMFA, q2= 0.843, r2= 0.930, F value= 266.755, SEE= 0.165; CoMSIA, q2= 0.869, r2= 0.918, F value= 222.571, SEE= 0.179) were obtained, and assessed the model's predictive capabilities by validating it with the test set.Conclusion Our findings indicate that the introduction of an appropriately sized structure at position 2 of the compound yields significant benefits. Conversely, the attachment of an excessively large group is detrimental. Direct attachment of a bulky substituent at C-6 of the compound is not feasible, and its activity increases when the structure with low electron cloud density is added. Moreover, the presence of a voluminous functional group at the 5' position of the compound is advantageous, and its activity will be further increased by the presence of hydrogen bond receptors in this region. These discoveries furnish significant comprehension for the formation of innovative structures with heightened efficacy.

Cardiovascular disease caused by platelet aggregation is a serious threat to human health, so antiplatelet aggregation has great significance to treat the disease. Since, purine derivatives are important molecules with antiplatelet aggregation activity, it is very essential to study the relationship between purine structure and antiplatelet aggregation effect, which could help us to find antithrombotic drugs. This article describes the modification of molecular substituents with purine structures as backbone and evaluates their antiplatelet aggregation activity. 3D-QSAR analysis of a series of novel purine derivatives synthesized was performed based on self-organized molecular field analysis (SOMFA). Significant correlation coefficients (SOMFA, r(2) = 0.821, r(cv)(2) = 0.807, F value = 283.500, SEE = 0.229) were obtained, and the model prediction ability was validated using the test set. The results suggest that rational modification of the substituent groups can provide a basis for the development of more effective drug molecules.

We need a practical, inexpensive, and green way to reduce the environmental pollutants, especially for dye wastewater. The discharge of industrial wastewater such as organic dyes will cause serious pollution to water bodies, thereby affecting people's lives. In this work, we designed and successfully synthesized four new ligand catalysts. The total outputs of diamide diamino iron ligand compounds A and B are 71.33% and 61.39%, respectively. The total outputs of polyaromatic iron tetraamido macrocyclic ligand (TAML) compounds C and D are 38.49% and 49.11%, respectively. The catalytic effects of four catalysts on the degradation of dye wastewater by hydrogen peroxide oxidation were studied and compared with the second‐generation Fe III ‐TAML catalyst. The experimental results showed that acyclic catalyst A and B has good catalytic effect. For methylene blue, methyl orange, rhodamine B three dyes wastewater, under the conditions of 20°C, C catalyst A = 0.056–0.28 mM and C hydrogen peroxide = 33 mM, the decolorization rate and chemical oxygen demand (COD) removal rate are 81.53%–97.58% and 52.2%–60.7%, respectively. Under the condition of 20°C, C catalyst B = 0.75 mM and C hydrogen peroxide = 33 mM, the decolorization rate and COD removal rate are 48.33%–80.33% and 44.6%–57.8%, respectively.

To reduce the cost of water treatment reagents, a simplified iron(III) tetraamido macrocyclic ligand compound (Fe-III-TAML) was synthesized with a total yield of 53.3%. For comparison, two second generation Fe-III-TAML catalysts were synthesized. The synthetic route was optimized, and the total yield increased from 30.1% to 49.5%. The catalytic activity of the simplified catalyst for degradation of dye wastewater by hydrogen peroxide was tested and compared with that of the second generation Fe-III-TAML catalysts. The experimental results show that the simplified catalyst has good catalytic activity. At 25 degrees C, pH = 8, CFe-TAML = 50 mg/L, and C-hydrogen peroxide = 1.5 g/L, the decolorization and chemical oxygen demand removal of methylene blue, methyl orange, neutral red, and Rhodamine B dye wastewater were 74.8%-96.1% and 46.9%-63.7%, respectively.

—In this study, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and the self-organizing molecular field analysis (SOMFA) were performed on a series of novel adenosine derivatives. Significant correlation coefficients (CoMFA, q2 = 0.560, r2 = 0.940, F value = 71.850, and SEE = 0.097; CoMSIA, q2 = 0.528, r2 = 0.943, F value = 29.29 and SEE = 0.108; SOMFA, r2 = 0.615, $$r_{{{\text{cv}}}}^{{\text{2}}}$$ = 0.577, F value = 60.797, and SEE = 0.226) were obtained, and the generated models were validated using test sets. By analyzing the corresponding contour maps in detail, new adenosine derivatives with potential efficacy were designed for synthesis in the future.

This article described how further extensive variation of the substituents on the purine scaffold of adenosine triphosphate (ATP), and the human anti-platelet aggregation activities were modified in order to find exploitation of the structure-activity relationships (SAR). A series of novel designed 6-alkylamino-2-alkylthio-9-hydroxyalkyl(carbalkoxy) purine derivatives were synthesized via a modification procedure, and the human anti-platelet aggregation activities were evaluated. The SAR of these compounds were analyzed in detail, and the results of the structural requirements of the substituents to improve potency may provide a basis for the development of potent P2Y(12) antagonists.

(R)-3二甲氨基吡咯烷是合成药物巴氟替尼的关键手性中间体.本文以L-苹果酸为起始原料,经过环化、还原、过磺酰化、脱保护等反应合成了(R)-3-二甲氨基吡咯烷,总收率31.45%,其结构经1 H NMR, 13 C NMR和IR确证.并对关键中间体的合成条件进行了优化.

血小板凝集导致的血栓类心血管疾病正严重威胁着人类健康,故而抵抗血小板凝集对血栓类心血管疾病的治疗至关重要.嘌呤衍生物是具有抗血小板凝集活性的重要分子,研究嘌呤结构与抗凝效果之间的关系,对治疗血栓类疾病药物的研发具有重要指导意义.本文采用自组织分子场(SOMFA)对29个新型腺嘌呤化合物结构与抗凝活性之间的关系进行3D-QSAR分析,建立最佳SOMFA模型,交叉验证系数r2可达0.87,非交叉验证系数r2cv可达0.83,统计方差比F值为183.41,标准方差s仅为0.05,表明该模型有较好的预测能力.测试集的r2pred为0.886,表明该模型对外部化合物的药物活性具有较为可靠的预测能力.同时,立体场和静电场的三维网格图显示了取代基空间体积及电荷分布规律对活性的影响,为下一步预测、设计及合成活性更高的抗凝集嘌呤分子提供理论指导.

A general approach for the synthesis of 2-alkylthio-N-6-aryladenosine was developed from the commercially available guanosine through the acetyl protection, chlorination, diazotization-alkylthionation, aromatic nucleophilic substitution and deacetylation. Two approaches were designed for the transformation of 2-amino-6-chloro-guanosine to 2-alkylthio-N-6-aryladenosines but only the one with diazotization-alkylthionation first could afford the target molecules. Both electron-rich and deficient anilines can afford the desired products in moderate to good yield. Finally, under the optimized condition, 20 2-alkylthio-N-6-aryladenosines were synthesized, 5 of which exhibit poor antiplatelet aggregation activities.

Background: Chronic Myelogenous Leukemia (CML) is a kind of blood and bone marrow cancer. Tyrosine Kinase Inhibitors (TKIs) play an important role in the treatment of Chronic Myelogenous Leukemia (CML). Objective: The aims of this study are to demonstrate the different binding mode of Benzothiazole-Based analogues with T315I mutant Bcr-Abl and wild-type Bcr-Abl. Methods: In this paper, Self-Organizing Molecular Field Analysis (SOMFA), a simple Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) analysis was performed on these 49 benzothiazole-based derivatives. Results: In this paper, highly predictive SOMFA models (r(2) = 0.748, r(cv)(2) = 0.720, F value = 124.9, and SEE = 0.761 for T3151 mutant Bcr-Abl, r(2) = 0.676, r(cv)(2) = 0.616, F value = 52.98, and SEE = 0.767 for wild-type Bcr-Abl) were obtained, and the generated models were validated using test sets. Conclusion: We obtained the best models of the training set and the statistical results for SOMFA model had a high predictive ability. The contour maps of potent compounds 9b was constructed by SOMFA method and some useful information was obtained for further designing new structures with high activity.

A practical and operationally simple protocol for the assembly of 6‐aryl‐substituted purines through the direct C6–H arylation of purines and 8‐azapurine and purine nucleosides from arylboronic acids was developed. This reaction was performed under ambient conditions with ammonium persulfate as the oxidant in the presence of silver(I). The reaction was found to be regioselective with the arylation occurring predominantly at the C6 position, and a large variety of functional groups, including halides, esters, hydroxy groups, and heterocycles, were tolerated.

The cover picture shows a silver-colored statue with a hand holding a triple helix, which can be found at the campus of the Beijing University of Chemical Technology. This DNA-like statue represents step-by-step chemical transformations, in this case the silver-catalyzed cross-coupling of purines and aryl boronic acids, shown as different balls at the bottom of the helix, to afford the final C6-arylated product, shown as the single ball at the top. Details are discussed in the Communication by N. Chen, H. Du et al. on page 3415 ff (https://doi.org/10.1002/ejoc.201700406).

Twenty 6-alkylamino-2-alkylthio adenosine derivatives with tested antiplatelet aggregation activity were subjected to a self-organized molecular field analysis (SOMFA),and a three-dimensional-quantitative structureactivity relationship (3D-QSAR) analysis.By using the multiple regression method,a best SOMFA model with good predictive functionality was generated with r2cv =0.801,r2 =0.807,F =75.281,and s =0.130.Analyzing the 3D electrostatic and shape potential master grid of this model provides a useful clear and intuitive theoretical guide for designing new antiplatelet aggregation inhibitors.

A highly regioselective C—H arylation of N 9 -arylpurines is developed in which aliphatic alcohols and PhI(OAc) 2 are used as alkoxylation reagent and oxidant, respectively.

AbstractThe method utilizes an inexpensive catalyst‐oxidant system, tolerates a broad range of substrates and proceeds well even on gram scale.

A palladium-catalyzed alkoxylation of N(9)-arylpurines with primary or secondary alcohols has been developed successfully, which is a rare C-H activation reaction of polynitrogenated purines and offers a late-stage strategy to synthesize N(9)-(ortho-alkoxyl)arylpurines. Although there are more than four nitrogen atoms present in the purine moiety, the reaction can be effectively conducted by sterically blocking the N(1) site for catalyst coordination and first employing the purinyl N(3) atom as a directing group.

A straight forward strategy to synthesize purine nucleosides with multiple functionalization on 2-, 6-, and 8-positions has been developed successfully, which provides a series of 8-alkoxy-6-alkylamino-2-alkylthiopurine nucleosides in moderate to good yields for further biological and medical activity screening. (C) 2016 Elsevier Ltd. All rights reserved.