152460-10-1Relevant articles and documents
Industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles-catalyzed hydrogenation of nitroarenes
Fu, Lihua,Li, Dingzhong,Lu, Hao,Qiu, Renhua,Sun, Tulai,Xing, Chen,Yang, Tianbao
, (2022/01/11)
The development of green and efficient methods for hydrogenation of nitroarenes is still highly demanding in organic synthesis. Herein, we report an industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles process for the synthesis of aryl amines with good yields via hydrogenation of nitroarenes. Nine key anti-cancer drug intermediates were successfully achieved with protocol. And Osimertinib intermediate 4m can be smoothly synthesized at a 2.67 kg-scale with >99.5% HPLC purity. This protocol features cheap carbon source, highly catalytic activity, simple operation, kilogram-scalable and recyclable catalysts (eight times without observable losing activity).
SYNTHESIS OF 6-METHYL-N1-(4-(PYRIDIN-3-YL)PYRIMIDIN-2-YL)BENZENE-1,3-DIAMINE
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, (2021/04/23)
Processes and useful intermediates for the synthesis of the tyrosine kinase inhibitors Formula (II) nilotinib and Formula (IV) imatinib. Key intermediates, method for their synthesis and their use in a divergent synthesis, making use of a Curtius rearrangement, to nilotinib and imatinib are described.
SUBSTITUTED ARYLUREA COMPOUNDS FOR INDUCING APOPTOSIS AND COMPOSITION FOR ANTICANCER COMPRISING THE SAME
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, (2021/08/17)
The present invention relates to a substituted arylurea compound inducing apoptosis and an anticancer composition comprising the same. The present invention relates to a novel compound capable of preventing, treating and alleviating cancer diseases such as prostate cancer, breast cancer, lung cancer, colorectal cancer, and skin cancer by inhibiting apoptosis of cancer cells and inhibiting proliferation of cancer cells.
Selective and Additive-Free Hydrogenation of Nitroarenes Mediated by a DMSO-Tagged Molecular Cobalt Corrole Catalyst
Sch?fberger, Wolfgang,Timelthaler, Daniel,Topf, Christoph
supporting information, p. 2114 - 2120 (2021/07/22)
We report on the first cobalt corrole that effectively mediates the homogeneous hydrogenation of structurally diverse nitroarenes to afford the corresponding amines. The given catalyst is easily assembled prior to use from 4-tert-butylbenzaldehyde and pyrrole followed by metalation of the resulting corrole macrocycle with cobalt(II) acetate. The thus-prepared complex is self-contained in that the hydrogenation protocol is free from the requirement for adding any auxiliary reagent to elicit the catalytic activity of the applied metal complex. Moreover, a containment system is not required for the assembly of the hydrogenation reaction set-up as both the autoclave and the reaction vessels are readily charged under a regular laboratory atmosphere.
Synthetic method of N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidinamine
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, (2020/08/02)
The invention discloses a synthetic method of N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidinamine. The synthetic method comprises the following steps: (1) synthesizing 2-(methylthio)-4-(3-pyridyl) pyrimidine; (2) synthesizing 2-(methylsulfonyl)-4-(3-pyridine) pyrimidine; (3) synthesizing N-(2-methyl-5-nitrophenyl)-4-(3-pyridyl)-2-pyrimidinamine and (4) synthesizing the N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidinamine. Synthesis raw materials used in the method are low in price and easy to obtain, reaction conditions are mild, the product yield and purity are high, and the methodis suitable for industrial production. Therefore, the synthetic method disclosed by the invention has good advantages in the aspects of production cost control, environmental friendliness and productquality improvement.
Synthesis method of imatinib and imatinib mesylate
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, (2020/05/02)
The invention relates to a synthesis method of imatinib and imatinib mesylate. The method comprises the following steps: condensing 3-acetylpyridine and N,N-dimethylformamide dimethyl acetal which aretaken as initial raw materials to obtain 3-dimethylamino-1-(3-pyridyl)-2-propen-1-one, then reacting with 2-methyl-5-nitrophenylguanidine nitrate to form a pyrimidine ring, performing nitro reductionto obtain N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine, amidating the N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine and 4-(chloromethyl)benzoyl chloride, performing affinitysubstitution with 1-methylpiperazine to obtain imatinib, and salifying the imatinib and methanesulfonic acid. The products obtained by the method have the advantages of few impurities, simplicity in post-treatment, high total yield, greenness, environmental protection and safety, and is suitable for a production process for large-scale industrial production of imatinib mesylate.
N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine derivative with medicine activity, and preparation method thereof
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, (2019/02/19)
The invention discloses an N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine derivative with medicine activity, and a preparation method thereof, and belongs to the technical field of medicine synthesis. The structural formula of the N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine derivative with medicine activity is shown in the description. The invention also discloses a preparation method for the N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine derivative with anti-cancer activity. The N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine derivative prepared with the preparation method has good inhibition activity for lung carcinoma cells A549, and has a potential for becoming an anti-tumor medicine.
One-pot propagation of (Hetero)Arylamines: Modular synthesis of diverse Amino-di(hetero)arylamines
Liang, Xueting,Xu, Liang,Li, Cuihua,Jia, Xin,Wei, Yu
, p. 721 - 731 (2019/01/08)
Formal propagation of (hetero)arylamine is achieved via a one-pot Buchwald–Hartwig C–N cross-coupling and nitro reduction sequence, enabling a rapid modular synthesis of diverse amino-di(hetero)arylamines from (hetero)arylamines and halogenated nitrobenzenes. Various functionalized aromatic amines with different electronic and steric environments can be efficiently prolongated to formally incorporate another arylamino fragments. This approach has been successfully applied in the synthesis of more than forty amino-di(hetero)arylamines. The applicability of this method has also been demonstrated in the synthesis of oligoanilines and the tyrosine-kinase inhibitor Imatinib.
Molecular requirements for the expression of antiplatelet effects by synthetic structural optimized analogues of the anticancer drugs imatinib and nilotinib
Alivertis, Dimitrios,Brentas, Alexios,Ntemou, Nikoleta,Pantazi, Despoina,Skobridis, Konstantinos,Tselepis, Alexandros D.
, p. 4225 - 4238 (2019/12/25)
Background: Platelets play important roles in cancer progression and metastasis, as well as in cancer-associated thrombosis (CAT). Tyrosine kinases are implicated in several intracellular signaling pathways involved in tumor biology, thus tyrosine kinase inhibitors (TKIs) represent an important class of anticancer drugs, based on the concept of targeted therapy. Purpose: The objective of this study is the design and synthesis of analogues of the TKIs imatinib and nilotinib in order to develop tyrosine kinase inhibitors, by investigating their molecular requirements, which would express antiplatelet properties. Methods: Based on a recently described by us improved approach in the preparation of imatinib and/or nilotinib analogues, we designed and synthesized in five-step reaction sequences, 8 analogues of imatinib (I–IV), nilotinib (V, VI) and imatinib/nilotinib (VII, VIII). Their inhibitory effects on platelet aggregation and P-selectin membrane expression induced by arachidonic acid (AA), adenosine diphosphate (ADP) and thrombin receptor activating peptide-6 (TRAP-6), in vitro, were studied. Molecular docking studies and calculations were also performed. Results: The novel analogues V–VIII were well established with the aid of spectroscopic methods. Imatinib and nilotinib inhibited AA-induced platelet aggregation, exhibiting IC50 values of 13.30 μΜ and 3.91 μΜ, respectively. Analogues I and II exhibited an improved inhibitory activity compared with imatinib. Among the nilotinib analogues, V exhibited a 9-fold higher activity than nilotinib. All compounds were less efficient in inhibiting platelet aggregation towards ADP and TRAP-6. Similar results were obtained for the membrane expression of P-selectin. Molecular docking studies showed that the improved antiplatelet activity of nilotinib analogue V is primarily attributed to the number and the strength of hydrogen bonds. Conclusion: Our results show that there is considerable potential to develop synthetic analogues of imatinib and nilotinib, as TKIs with antiplatelet properties and therefore being suitable to target cancer progression and metastasis, as well as CAT by inhibiting platelet activation.
Synthesis and biological evaluation of phenyl-amino-pyrimidine and indole/oxindole conjugates as potential BCR-ABL inhibitors
Rahim, Abdul,Syed, Riyaz,Poornachandra,Malik, M. Shaheer,Reddy, Ch. Venkata Ramana,Alvala, Mallika,Boppana, Kiran,Sridhar,Amanchy, Ramars,Kamal, Ahmed
, p. 633 - 645 (2019/03/23)
Abstract: Indole/isatin conjugated phenyl-amino-pyrimidine derivatives have been synthesized, characterized and evaluated in vitro for their potential as BCR-ABL inhibitors. Among the series, all derivatives (7a–7o) were found to be more cytotoxic than standard Imatinib against K-562 cell line. Compound 7l was the most active in the series with almost two folds more potency than imitanib (IC50 0.65 μM). In vitro enzymatic studies with recombinant ABL kinase enzyme exhibited promising inhibition in the range of 30–71 μM for most of these novel conjugates. In addition, modelling and other computational studies have been carried out to draw insight into the BCR-ABL protein interactions with the target molecules and drug like properties of the conjugates, respectively. [Figure not available: see fulltext.].
