619-31-8Relevant academic research and scientific papers
Detailing the elementary stages in the oxirane ring opening reactions with carboxylic acids catalyzed by tertiary amines
Bakhtin, Stanislav,Shved, Elena,Bespalko, Yuliia,Tyurina, Tatyana,Palchykov, Vitalii
, (2020)
The study of the reaction systems “R3N – proton-donor reagent (NuH) – epichlorohydrin” using a complex of various kinetic methods of investigation allowed the reaction pathway and the catalysis mechanism of the oxirane ring opening by proton-donor reagents in the presence of R3N to be detailed. It was confirmed that the catalytic activity of R3N consists in their quaternization by oxirane under the obligatory condition of its electrophilic assistance with the NuH reagent. The quaternization process of tertiary amines was studied using 1H NMR and UV spectroscopy, quantum chemical modeling, and correlation analysis. It was shown that the transition states of the quaternization stage are dissociative, and their degree of looseness depends on the electrophilic activation of the oxirane ring.
PYRIMIDINE COMPOUND, PREPARATION METHOD THEREOF AND MEDICAL USE THEREOF
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Paragraph 0823; 0824, (2021/04/10)
The present invention discloses a pyrimidine compound, a preparation method thereof and a medical use thereof. Specifically, the present invention discloses a pyrimidine compound represented by formula (I), pharmaceutically acceptable salts thereof, a preparation method thereof, and a use thereof as a cyclin-dependent kinase 9 (CDK9) inhibitor, particularly for the treatment of cancer. The definition of each group in formula (I) is the same as that in the specification.
Amination of Aromatic Halides and Exploration of the Reactivity Sequence of Aromatic Halides
Yang, Chu,Zhang, Feng,Deng, Guo-Jun,Gong, Hang
, p. 181 - 190 (2019/01/10)
A base-promoted amination of aromatic halides has been developed using a limited amount of dimethylformamide (DMF) or amine as an amino source. Various aryl halides, including F, Cl, Br, and I, have been successfully aminated in good to excellent yields. Although the amination of aromatic halides with amines or DMF is usually considered as an aromatic nucleophilic substitution (SNAr) process, and the reactivity of an aromatic halide is F > Cl > Br > I, the reactivity of aromatic halides in this system was found to be I > Br a‰ F > Cl. This protocol also showed a good regioselectivity for multihalogenated aromatics. This protocol is valuable for industrial application due to the simplicity of operation, the unrestricted availability of amino sources and aromatic halides, transition metal-free conditions, no requirement for solvent, and scalability.
Efficient and versatile catalytic systems for the n-methylation of primary amines with methanol catalyzed by n-heterocyclic carbene complexes of iridium
Toyooka, Genki,Tuji, Akiko,Fujita, Ken-Ichi
, p. 4617 - 4626 (2019/02/01)
Efficient and versatile catalytic systems were developed for the N-methylation of both aliphatic and aromatic primary amines using methanol as the methylating agent. Iridium complexes bearing an Nheterocyclic carbene (NHC) ligand exhibited high catalytic performance for this type of transformation. For aliphatic amines, selective N,N-dimethylation was achieved at low temperatures (50-90 °C). For aromatic amines, selective N-monomethylation and selective N,N-dimethylation were accomplished by simply changing the reaction conditions (presence or absence of a base with an appropriate catalyst). These findings can be used to develop methods for synthesizing useful amine compounds having N-methyl or N,N-dimethyl moieties.
Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)
Lu, Yanli,Mao, Fei,Li, Xiaokang,Zheng, Xinyu,Wang, Manjiong,Xu, Qing,Zhu, Jin,Li, Jian
supporting information, p. 5099 - 5119 (2017/06/28)
Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFRα) kinases play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFRα dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRα. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PDGFRα-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 μM concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T670I tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.
Deoxygenation of tertiary amine N-oxides under metal free condition using phenylboronic acid
Gupta, Surabhi,Sureshbabu, Popuri,Singh, Adesh Kumar,Sabiah, Shahulhameed,Kandasamy, Jeyakumar
supporting information, p. 909 - 913 (2017/02/15)
A simple and efficient method for the deoxygenation of amine N-oxides to corresponding amines is reported using the green and economical reagent phenylboronic acid. Deoxygenation of N,N-dialkylaniline N-oxides, trialkylamine N-oxides and pyridine N-oxides were achieved in good to excellent yields. The reduction susceptible functional groups such as ketone, amide, ester and nitro groups are well tolerated with phenylboronic acid during the deoxygenation process even at high temperature. In addition, an indirect method for identification and quantification of tert-amine N-oxide is demonstrated using UV–Vis spectrometry which may be useful for drug metabolism studies.
Direct oxidative cyanation of tertiary amines promoted by in situ generated hypervalent iodine(III)-CN intermediate
Shen, Hang,Zhang, Xiaohui,Liu, Qing,Pan, Jing,Hu, Wen,Xiong, Yan,Zhu, Xiangming
supporting information, p. 5628 - 5631 (2015/09/21)
An environmentally benign and metal-free cyanation method of tertiary amines oxidated by hypervalent iodine(III) intermediate generated in situ from PIFA (or DIB) and TMSCN has been developed. A variety of substituent groups on amines are tolerated to the oxidation of α-C-H bond to form C-C bond in the absence of metal catalysts with yields of up to 74%.
NOVEL TRICYCLIC DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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Page/Page column 51, (2011/10/04)
The present invention relates to a novel tricyclic derivative with efficient inhibitory activity against poly(ADP-ribose)polymerases (PARP) or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition containing the same. The tricyclic derivative of the invention is useful for the prevention or treatment of diseases caused by excess PARP activity, especially neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic nephropathy, inflammatory diseases, osteoporosis, and cancer, by inhibiting the activity of poly(ADP-ribose)polymerases.
NOVEL TRICYCLIC DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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Page/Page column 42, (2011/10/02)
The present invention relates to a novel tricyclic derivative with efficient inhibitory activity against poly(ADP-ribose)polymerases (PARP) or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition containing the same. The tricyclic derivative of the invention is useful for the prevention or treatment of diseases caused by excess PARP activity, especially neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic nephropathy, inflammatory diseases, osteoporosis, and cancer, by inhibiting the activity of poly(ADP-ribose)polymerases.
