JOURNAL OF CHEMICAL RESEARCH
·
2015
·
IF 0.633
Haidong Liu,Yuan Li,Dongdong Wang,Yu Qin,Min Ji
A convenient route for the synthesis of Novartis's second-generation anaplastic lymphoma kinase inhibitor Ceritinib (LDK378) involving starting materials that are commercially available has been achieved. The procedure employed mild reaction conditions and avoided the use of expensive reagents compared to the original synthetic route reported by Novartis. More importantly, gram scale synthesis was accomplished and this protocol could be valid in drug discovery synthesis.
研究领域:
药物化学
·
有机合成
·
肿瘤学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 15
·9256-9262
·
IF 4.036
Mengmeng Zhao,Xiaoxia Wu,Zengda Yu,Yunkai Sun,Zhao Liu,Jinqiao Yuan,Hu Liu,Yiping Jin
Avanafil is a phosphodiesterase type 5 inhibitor which is used to treat erectile dysfunction in men. The process-related impurities of avanafil were investigated, and four kinds of impurities in several laboratory batches with a content of 0.29–1.63% were detected by the newly developed gradient ultra-high performance liquid chromatography (UPLC). Based on the synthesis route and UPLC-MS research, the impurities are inferred as Imp-A, Imp-B, Imp-C and Imp-D. The structures of the impurities were inferred from LC-MS studies and confirmed by synthesis, followed by spectroscopic characterization such as NMR and mass spectrometry. Especially, the synthesis of Imp-D is firstly reported. The drug-related substances can be separated well by efficient and selective ultra-high performance liquid chromatography on a Waters ACQUITY HSS C18 (50 × 2.1 mm, particle size 1.8 μm) column at 35 °C, with the mobile phase consisting of ammonium formate (20 mM) and acetonitrile, and the detection at 239 nm with a DAD detector. The method was validated in terms of specificity, linearity, precision, accuracy and sensitivity, and satisfactory results were obtained. The results indicated this developed UPLC method for avanafil and the proposed synthesis mechanism can be used for quality control purposes as required by regulatory agencies to ensure the safety and efficacy of the product.
研究领域:
药物化学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MONATSHEFTE FUR CHEMIE
·
2023
·Vol. 155
·期 1
·99-104
·
IF 1.8
Dong Wenwen,Gong Tengfei,Liu Chaoyang,Lin Jia,Jia Qiang,Chu Changhu
Apixaban is a highly potent, selective, and efficacious inhibitor of blood coagulation factor Xa. A practical and efficient process has been developed for the preparation of the key intermediate of apixaban. Starting from inexpensive 4-chloronitrobenzene and piperidine, an eight-step procedure for the intermediate has been developed. In this case, sodium chlorite is used twice to oxidize the piperidine cycle to the corresponding lactam under a CO 2 atmosphere, resulting in the construction of two lactams. Furthermore, most of these reactions are highly efficient and practical as they occur under mild conditions. Most of the intermediates can be obtained through simple slurry or recrystallization, and column chromatography purification is not necessary. Graphical abstract
研究领域:
药物化学
·
有机合成
✓ 已验证
DOI
高影响因子
JOURNAL OF POLYMERS AND THE ENVIRONMENT
·
2023
·Vol. 31
·期 8
·3573-3584
·
IF 5.3
Chen Zixuan,Sun Fei,Zhao Huakun,Yu Tao,Yang Weidong,Li Qian,Li Yan
Poly (lactic acid) (PLA) is a bio-based polymer that is derived from renewable plant resources, such as corn, cassava, and other crops. It has a wide range of potential applications. However, currently, the PLA produced on an industrial scale is a thermoplastic polymer, which has poor mechanical strength and poor flame retardancy. These mediocre properties limit its potential uses in housings, structural interior of automotives, and packaging. The present study aimed to overcome the limitations of thermoplastic PLA by developing a synthesis route for producing thermosetting PLA with improved flame retardancy. The synthesis involved reacting 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) with itaconic acid (IA), polymerizing the product with pentaerythritol (PENTA) and lactic acid (LA) oligomer, and end-functionalizing with methacrylic anhydride (MAAH). The success of the synthesis was confirmed by analyzing the results of Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance ( 1 H NMR) analysis. The curing kinetics is elaborated by Kissinger’s and Crane’s methods with outstanding fitting. Increasing the LA-to-PENTA ratio results in higher molecular weight and larger arm length, leading to less crosslinking density and lower phosphorus content. A 10:1 LA-to-PENTA mole ratio contributes to UL-94 V1 ranking, 24% limit oxygen index (LOI), 183 kJ/g heat release capacity (HRC), and 21.4 kJ/g total heat release (THR) indicating the admirable flame retardancy. The development of flame-retardant thermosetting PLA could be a significant step forward in expanding its potential applications and improving its properties.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AOAC INTERNATIONAL
·
2019
·Vol. 99
·期 3
·638-648
·
IF 1.201
Ma Xingling,Liu Lei,Cao Na,Zou Qiaogen,Xiong Kaihe,Ouyang Pingkai
Palbociclib is the first U.S. Food and Drug Administration-approved cyclin-dependent kinase inhibitor indicated in combination with letrozole for the treatment of breast cancer. Development of a selective method for the determination of any impurities contained in this drug is significantly important to ensure the quality and safety of palbociclib. In this study, a reliable reversed-phase HPLC method for the separation and determination of eight potential impurities was developed and validated. The structures of two new compounds and six other process-related impurities were characterized and confirmed by MS, NMR, and IR. Based on spectral analysis and available knowledge of the synthetic route of palbociclib, these two new compounds were designated as 6-acetyl-8-cyclopentyl-5-methyl-2-{[3-(piperazin-1-yl)pyridin-2yl]amino}pyrido [2,3-d]pyrimidin-7(8H)-one and 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(4-t-butyloxycarbonyl-)-(piperazin-1-yl)pyridin-2yl]amino}pyrido [2,3-d]pyrimidin-7(8H)-one. The developed method was validated for accuracy, precision, linearity, sensitivity, robustness, and solution stability.
研究领域:
药学
·
分析化学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL PAPERS
·
2014
·Vol. 68
·期 10
·1408-1414
·
IF 1.193
Cao Meng,Hu Hua-You,Zhao Hu-Cheng,Zhang Xi-Quan,Gu Hong-Mei,Yang Ling,Cai Jin,Wang Peng,Hu Bing,Ji Min
In the current study a facile synthetic route for preparing antineoplastic drug GDC-0449 is investigated. Starting with pyridine-1-oxide and 1-iodo-3-nitrobenzene, the intermediate product 2-(2-chloro-5-nitrophenyl) pyridine was prepared by cross-coupling, deoxidation and halogenation. The final compound was then synthesised by reduction of the nitro group followed by amidation. This synthetic route avoids the use of unstable organometallic or organic boride compounds; it employs relatively inexpensive and bench-stable reagents, involves readily controllable reaction conditions, and achieves a relatively high yield.
研究领域:
药物化学
·
有机合成
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2015
·
IF 0.633
Haidong Liu,Yongfeng Lv,Yuan Li,Jin Cai,Junqing Chen,Yu Qin,Min Ji
A convenient route for the synthesis of a third-generation epidermal growth factor receptor inhibitor, mereletinib (AZD9291) using starting materials that are commercially available has been achieved through reactions that are readily conducted under mild conditions. Importantly, a 5 g scale synthesis was also accomplished and this method could therefore be useful in the synthesis of similar drugs.
研究领域:
药物化学
·
有机合成
·
肿瘤学
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 33
·期 2
·2210095
·
IF 19.924
Jiao Chen,Jun Bo Luo,Mu Yuan Hu,Jun Zhou,Cheng Zhi Huang,Hui Liu
Carbon dots (CDs) have received extensive attention and applications in recent years due to their remarkable characteristics of tunable emission wavelength, high stability, and a variety of synthetic raw materials. Since the formation process and photoluminescence properties of CDs are affected by multiple factors, the luminescence regulation of CDs has always been a troublesome problem. Furthermore, it is still a lack of appropriate approaches to reveal the hidden rules between the synthesis conditions and the luminescence properties of CDs. Inspired by machine learning (ML) applications in molecular and materials science, herein, a data-driven ML strategy is proposed to multi-dimensionally investigate the correlation between reaction parameters and the photoluminescence properties of CDs. Meanwhile, it is demonstrated that reaction parameters and solvent properties have different influences on the fluorescence properties of CDs, and the intelligently optimizing synthesis route of CDs is achieved using ML algorithms. CDs with excellent luminescent properties screened by ML are further applied to high-capacity colorful information encryption. This study provides an efficient ML-assisted strategy to guide the synthesis of multicolor CDs, helping researchers to quickly and easily obtain CDs according to experimental requirements.
研究领域:
材料科学
·
化学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 30
·21432-21438
·
IF 3.9
Yunkai Sun,Xiaoxia Wu,Pei Zuo,Zhao Liu,Xuepei Miao,Jian Liu,Hairuo Wen
In the technical route for the synthesis of avanafil, 1-ethyl-(3-dimethylaminopropyl)carbamyldiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBT) are used as reactive acid–amine binding agents. HOBT contains trace amounts of hydrazine residue, and there is a risk of introducing potentially mutagenic impurities with hydrazide-containing structures. The potentially genotoxic impurities E (Imp-E) and F (Imp-F) of avanafil with altering hydrazide-structure were synthesized by chemical method; subsequently, the impurities were evaluated and classified according to ICH M7 guidelines. Two complementary quantitative structure–activity relationship (QSAR) evaluation systems (Derek and Sarah) based on expert rules and statistics were used to preliminarily predict the genotoxicity of Imp-E and Imp-F, and the prediction result of E was suspected to be positive. In the Ames test of Imp-E and Imp-F, in the dose range of 62.5–1000 μg per plate, with or without the presence of metabolic activation system S9, the number of revertant colonies did not exceed 2 times the number of colonies in the solvent control group and did not show a dose–response relationship, and the test results were negative. Imp-E and Imp-F were determined to be negative for genotoxicity, which could be controlled as class 5 in ICH M7, that is, non mutagenic impurity.
研究领域:
药物化学
·
毒理学
·
制药工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2018
·
IF 0.668
Yamu Xia,Lijia Zou,Jiahong Zhang,Wen Zhang
Leoligin, a tetrahydrofuran lignan isolated from the root of the edelweiss plant, was synthesised from veratraldehyde (2 mol), diethyl succinate and 2-methyl-(Z)-2-butenoic acid. Initially, veratraldehyde and diethyl succinate underwent a Stobbe condensation to yield a C6-C5 acid which, after esterification, was condensed with a second molecule of veratraldehyde to generate a 2,3,4-trisubsituted γ-butyrolactone intermediate. Two reduction steps yielded a triol, which was ring-closed with tosyl chloride to form a hydroxymethyl-tetrahydrofuran, esterification of which with 2-methyl-(Z)-2-butenoic acid generated leoligin.
研究领域:
有机化学
·
植物化学
✓ 已验证
DOI
高影响因子
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY
·
2017
·Vol. 53
·期 3
·459-461
·
IF 0.603
Liu X. J.,Yan Y. N.,Wang S. Q.,Li X.,Liu X. G.
A new synthetic route to 4-methoxyisophthalic acid, the key intermediate in the synthesis of Picotamide, is reported. The new protocol starts from commercially available and cheap 4-methylphenol and includes four steps: esterification, Fries rearrangement, methylation, and oxidation; the overall yield is 49%. Unlike the traditional Blanc chloromethylation/oxidation scheme, the proposed procedure avoids using volatile and corrosive hydrochloric acid.
研究领域:
有机化学
·
药物化学
✓ 已验证
DOI
高影响因子
JOURNAL OF LUMINESCENCE
·
2020
·
IF 3.28
Lei Chen,Zhuming Cheng,Guifang Zheng,Gang Yao,Liangrui He,Lei Wang,Jianzhe Liu,Haiwu Zheng,Shizhong Wei,Haiyong Ni
The green-emitting phosphor SrSi 2 O 2 N 2 : Eu 2+ , along with the cyan-emitting phosphor BaSi 2 O 2 N 2 : Eu 2+ , is a key component for phosphors used to package natural sunlight full-spectrum LED devices. Thereby, the synthesis of high-efficiency and thermal-stability luminous SrSi 2 O 2 N 2 : Eu 2+ with an economic approach is very important for the development of LED industry. In this work, the syntheses of SrSi 2 O 2 N 2 : Eu 2+ phosphors were optimized from four aspects: strontium sources, reaction atmospheres, reaction vessels, and reaction fluxes. Meanwhile, the relationship among photoluminescence performances, crystal structures, and morphologies were examined. The results show that the synthesis of SrSi 2 O 2 N 2 : Eu 2+ from SrO and Sr(NO 3 ) 2 sources are beneficial to obtain N-rich oxynitide structure, which is helpful to improve luminescence. By employing SrCO 3 and Sr(NO 3 ) 2 as strontium sources, however, the SrSi 2 O 2 N 2 : Eu 2+ is O-rich and the by-product Sr 2 Si 5 N 8 :Eu is introduced. The optimal conditions for the synthesis of SrSi 2 O 2 N 2 : Eu 2+ is by utilizing SrO as a strontium source, in N 2 atmosphere, adopting Mo crucible, and adding NH 4 Cl as flux. The quantum yield of the optimal SrSi 2 O 2 N 2 : Eu 2+ phosphor under the excitation of 380 nm reaches up to 100%.
研究领域:
材料科学
·
光学工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）