Preparation of Highly Water-soluble Platinum Antitumor Drugs and Evaluation of Antitumor Efficacy on Tumor Cell Lines / 中国药学杂志

OBJECTIVE: To design and synthesize a new kind of highly water-soluble platinum antitumor compounds, and then evaluate their cytotoxicity in order to confirm their antitumor efficacy. METHODS: Diamide-diiodide platinum was firstly synthesized from potassium chloroplatinate, which was then reacted with Ag2SO4 to obtain intermediate . Using disodium 2-amino-alkyl malonate or N-substituted amino alkyl malonate as the intermediate Ⅱ, the two intermediates reacted at 1∶1 molar ratio to obtain the target compound III in the presence of acid. RESULTS: A new class of platinum compounds were synthesized, which had much better water solubility than that of the existing three-generation platinum compounds. Their antitumor efficacy was confirmed against a variety of tumor cell lines which was higher than that of carboplatin. IIIg was similar to cisplatin in antitumor efficacy on some tumor cell lines. Some target compounds were effective against cisplatin-resistant cell lines. CONCLUSION: Currently in the clinical trial, the target compound IIIg is a new platinum-base antitumor candidate, which exhibits good water solubility and antitumor efficacy in vitro, and the LD50 based on mice shows its lower toxicity than that of cisplatin and carboplatin in vivo.

Improved Synthesis Process of Pivotal Intermediate of SKI2496 in Kilogram Scale / 中国药学杂志

OBJECTIVE: To establish a preparation process of pivotal intermediate of SKI2496, which is low-cost, environmental-friendly and suitable for industrialization as well. METHODS: 1-(2-Fluoro-6-(trifloromethyl)benzyl)urea(2) was synthesized from 2-fluoro-6-(trifluoromethyl)benzylamine(1) with urea,followed by aminolysis with t-butyl acetoacetate and cyclization to give 1--6-methylpyrimidine-2,4(1H,3H)-dione(4).Finally,the title product was obtained via bromation and condensation reaction with piperazine. RESULTS: The synthetic process included four steps with an overall yield of 44.6%(based on compound 1) and its structure was confirmed by 1H-NMR and MS. CONCLUSION: The process is easy to operate, safe and suitable for industrial production.

3D printing technology and pharmacy research / 中国药学杂志

3D printing, as a new rapid prototyping technology, has been widely used in the aerospace, medicine, industry, cultural relics protection, and other fields. This paper made a brief summary of the study and application of 3 D printing in drug synthesis, pharmaceutical preparation, pharmaceutical analysis, and new drug research. The future applications and challenges of 3D printing technology were also discussed. This paper aims to provide a reference for the use of 3 D printing technology in the study of pharmacy.

Planejamento e sintese de compostos potencialmente ligantes dos receptores 5-HT2C e H4 / Design and synthesis of compounds potentially ligands of 5-HT2C e H4

A serotonina e a histamina são duas das mais importantes aminas biogênicas do organismo. Regulam série de funções fisiológicas, como fluxo sanguíneo, temperatura corpórea, sono, fome, liberação de hormônios, comportamento afetivo e humor, entre outras. Assim, há grande interesse no planejamento e desenvolvimento de fármacos que interferem na transmissão serotoninérgica e histaminérgica, para futura aplicação como antidepressivos, antipsicóticos, ansiolíticos e anorexígenos, além de perifericamente, apresentarem possíveis ações antiinflamatórias. O objetivo deste trabalho é apresentar a síntese de compostos contendo os núcleos pirrolquinolínico, benzoindólico e benzodiidrofurânico com potencial atividade ligante nos receptores 5-HT2C e H4, assim como avaliar a seletividade desses compostos em comparação aos receptores 5-HT2A/B e H3. Sintetizou-se série de compostos utilizando reações de alilação, adição à carbonila, termociclização, rearranjo de Claisen, iodociclização e substituição nucleofílica para a obtenção dos compostos finais. Estudos de otimização de síntese por metodologia de superfície de resposta também são apresentados, assim como estudos de relações quantitativas entre estrutura química e atividade biológica de compostos ligantes dos receptores 5-HT2C e H4

Serotonin and histamine are two major biogenic amines in the body. They regulate several physiological functions such as blood flow, body temperature, sleep, hunger, hormone release, emotional behavior and mood, among others. Thus, there is great interest in the design and development of drugs that interfere with serotoninergic and histaminergic transmission, for future use as antidepressants, antipsychotics, anxiolytics and anorectic, and peripherally, possible anti-inflammatory actions. The aim of this work is to present the synthesis of compounds containing the pyrroloquinoline, benzoindole and benzodihydrofurane nucleus with potential binding activity to 5-HT2C and H4 receptors, as well as to evaluate the selectivity of these compounds in comparison to 5-HT2A/B and H3. Series of compounds were synthesized using allylation, carbonyl addition, thermal cyclization, Claisen rearrangement, iodocyclization and nucleophilic substitution reactions. Optimization studies for the synthesis using response surface methodology are also presented, as well as quantitative structure-activity relationships studies of ligands of 5-HT2C and H4 receptors

Understanding of Multimedia Courseware Design of Reactions for Drug Synthesis / 国际中医中药杂志

This article offers some suggestions to the design and making of multimedia courseware. Combining teaching practice, speaks of the application of multimedia courseware and important significance during Organic Reactions for Drug Synthesis teaching.

Design and Synthesis of New γ-Secretase Inhibitors / 华中科技大学学报(医学版)

Objective By virtual screening in MDL,to search for a novel γ-secretase inhibitor.Methods A series of compounds were designed,synthesized,and evaluated based on pharmacophore model of γ-secretase inhibitors by virtual screening in MDL.Results The drug-likeness analytic data synthesized indicated that target compounds had drug-likeness.Each svnthesized compound was checked by IR spectroscopy,~1H and ~(13)C-NMR spectroscopy.Conclusion The designed compounds had better activity by model prediction.And the optimal compound showed a significant estimated activity value of 0.025 nmol/L and can be used as a lead for further drug development.