6162-76-1Relevant academic research and scientific papers
Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy
Rana, Sandeep,Sonawane, Yogesh A.,Taylor, Margaret A.,Kizhake, Smitha,Zahid, Muhammad,Natarajan, Amarnath
supporting information, p. 3736 - 3740 (2018/10/24)
We synthesized a library of aminopyrazole analogs to systematically explore the hydrophobic pocket adjacent to the hinge region and the solvent exposed region of cyclin dependent kinases. Structure-activity relationship studies identified an optimal substitution for the hydrophobic pocket and analog 24 as a potent and selective CDK2/5 inhibitor.
Preparation method of cytosine intermediate 3,3-diethoxypropionitrile
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Paragraph 0022; 0023, (2017/02/17)
The invention discloses a preparation method of cytosine intermediate 3,3-diethoxypropionitrile. The preparation method comprises following steps: 1) acetonitrile is taken as a raw material, and is reacted with tert-butyl hydroperoxide (TBHP) in the presence of a catalyst, and an obtained product and carbon monoxide are subjected to carbonylation reaction so as to obtain nitrile acetaldehyde; and step 2, nitrile acetaldehyde is reacted with ethanol in the presence of acid alcohol of a catalytic amount so as to obtain 3,3-diethoxypropionitrile. Obtained 3,3-diethoxypropionitrile can be subjected to condensation reaction with urea so as to prepare cytosine, synthesis effect is excellent, and the quality of obtained cytosine is high. Reaction mechanism of the preparation method is different from reaction mechanism of the prior art in which acetonitrile hydrogen protons are captured by strong base; in the preparation method, acetonitrile hydrogen protons are captured via free radical reaction so as to obtain acetonitrile free radicals; the acetonitrile free radicals are subjected to carbonylation reaction with carbon monoxide so as to obtain nitrile acetaldehyde directly; and nitrile acetaldehyde is transformed into 3,3-diethoxypropionitrile in the presence of acid alcohol of a catalytic amount.
Discovery and characterization of a novel 7-aminopyrazolo[1,5-a]pyrimidine analog as a potent hepatitis C virus inhibitor
Hwang, Jong Yeon,Windisch, Marc Peter,Jo, Suyeon,Kim, Keumhyun,Kong, Sunju,Kim, Hyoung Cheul,Kim, Soohyun,Kim, Heeyoung,Lee, Myung Eun,Kim, Youngmi,Choi, Jihyun,Park, Dong-Sik,Park, Eunjung,Kwon, Jeongjin,Nam, Jiyoun,Ahn, Sujin,Cechetto, Jonathan,Kim, Junwon,Liuzzi, Michel,No, Zaesung,Lee, Jinhwa
, p. 7297 - 7301 (2013/02/23)
We describe a novel 7-aminopyrazolo[1,5-a]pyrimidine (7-APP) derivative as a potent hepatitis C virus (HCV) inhibitor. A series of 7-APPs was synthesized and evaluated for inhibitory activity against HCV in different cell culture systems. The synthesis and preliminary structure-activity relationship study of 7-APP are reported.
UV-laser photochemistry of isoxazole isolated in a low-temperature matrix
Nunes, Claudio M.,Reva, Igor,Pinho E Melo, Teresa M. V. D.,Fausto, Rui
, p. 8723 - 8732,10 (2020/09/15)
The photochemistry of matrix-isolated isoxazole, induced by narrowband tunable UV-light, was investigated by infrared spectroscopy, with the aid of MP2/6-311++G(d,p) calculations. The isoxazole photoreaction starts to occur upon irradiation at λ = 240 nm, with the dominant pathway involving decomposition to ketene and hydrogen cyanide. However, upon irradiation at λ = 221 nm, in addition to this decomposition, isoxazole was also found to isomerize into several products: 2-formyl-2H-azirine, 3-formylketenimine, 3-hydroxypropenenitrile, imidoylketene, and 3-oxopropanenitrile. The structural and spectroscopic assignment of the different photoisomerization products was achieved by additional irradiation of the λ = 221 nm photolyzed matrix, using UV-light with λ ≥ 240 nm: (i) irradiation in the 330 ≥ λ ≥ 340 nm range induced direct transformation of 2-formyl-2H-azirine into 3-formylketenimine; (ii) irradiation with 310 ≥ λ ≥ 318 nm light induced the hitherto unobserved transformation of 3-formylketenimine into 3-hydroxypropenenitrile and imidoylketene; (iii) irradiation with λ = 280 nm light permits direct identification of 3-oxopropanenitrile; (iv) under λ = 240 nm irradiation, tautomerization of 3-hydroxypropenenitrile to 3-oxopropanenitrile is observed. On the basis of these findings, a detailed mechanistic proposal for isoxazole photochemistry is presented.
PREPARATION METHODS OF 6-SUBSTITUTED AMINO-3-CYANOQUINOLINE COMPOUNDS AND THE INTERMEDIATES THEREOF
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Page/Page column 10, (2011/11/06)
The present invention relates to a method for preparing 6-substituted amino-3-cyanoquinoline compounds (compound A for short) and the intermediates thereof, more particularly, to a compound of the following formula (I), the preparation method thereof, the intermediates thereof and use thereof for preparing the compound A. The compound of the formula (I) is cyclized in the presence of an alkali to give a compound of formula A, wherein W is OH; or the compound of the formula (I) is cyclized in the presence of an alkali, and then chlorinated to give a compound of the formula A, wherein W is Cl. Compared with the known methods in the literature, the method for preparing the compound A from the compound of formula (I) according to the present invention can avoid using high-temperature condition and high boiling point solvents, and is safe and environment-friendly, mild in reaction condition, easy in operation with a high yield and high product purity.
Design, synthesis, and in vitro antitumor activity evaluation of novel 4-pyrrylamino quinazoline derivatives
Wu, Xiaoqing,Li, Mingdong,Tang, Wenhua,Zheng, Youguang,Lian, Jiqin,Xu, Liang,Ji, Min
experimental part, p. 932 - 940 (2012/03/11)
Here, we describe the design and synthesis of two series of 4-pyrrylamino quinazolines as new analogs of the epidermal growth factor receptor inhibitor gefitinib. In vitro antitumor activity of these novel compounds against pancreatic (Miapaca2) and prostate (DU145) cancer cell lines was evaluated. Compared with the parental gefitinib, all 18 derivatives show a greatly increased cytotoxicity to cancer cells. In vitro kinase inhibitory activity on epidermal growth factor receptor was also investigated. Among them, compounds GI-6, GII-4, GII-6, GII-8, and GII-9 are more potential receptor tyrosine kinase (RTK) inhibitors. Based on these results, we propose simple structure-activity relationship to provide information for designing and developing more potent antitumor agents.
Synthesis of bosutinib from 3-methoxy-4-hydroxybenzoic acid
Yin, Xiao Jia,Xu, Guan Hong,Sun, Xu,Peng, Yan,Ji, Xing,Jiang, Ke,Li, Fei
experimental part, p. 4261 - 4266 (2010/09/18)
This paper reports a novel synthesis of bosutinib starting from 3-methoxy-4-hydroxybenzoic acid. The process starts with esterification of the starting material, followed by alkylation, nitration, reduction, cyclization, chlorination and two successive amination reactions. The intermediates and target molecule were characterized by 1H-NMR, 13C-NMR, MS and the purities of all the compounds were determined by HPLC.
Mass spectrometric study of the thermal decomposition mechanism of vapors of 2,2,6,6-tetramethyl-3-iminoheptane-5-one and its copper(II) complex
Turgambaeva, Assia E.,Krisyuk, Vladislav V.,Stabnikov, Pavel A.,Igumenov, Igor K.
, p. 5001 - 5006 (2008/03/13)
Thermal conversions of vapors of ketoimine C(CH3)3C(NH)CH2C(O)C(CH3)3 (Htmha = 2,2,6,6-tetramethyl-3-iminoheptane-5-one) and its chelate coordination compound with copper Cu(tmha)2 is studied by in situ mass spectrometry in a vacuum and in the presence of hydrogen. Experiments are carried out under conditions close to low pressure chemical vapor deposition at the evaporator temperature of 130 °C and the reactor temperature range 130-500 °C. It is found that compounds are monomeric in the gas phase. Based on temperature dependences of the composition of primary gaseous products, the mechanism of thermal decomposition is proposed. The decomposition of ketoimine on the heated surface begins at 350 ± 10 °C and proceeds by the elimination of terminal groups. Its copper complex decomposes in two directions and yields both molecular and radical products. The latter provide the assumption that metallic copper forms as the only one solid product. The results obtained are compared with those for copper dipivaloylmethanate(2,2,6,6-tetramethylheptane-3,5-dionate).
Hydrogen peroxide oxidation of 2-cyanoethanol catalyzed by metal complexes
Veghini,Shul'pina,Strelkova,Shul'pin
, p. 167 - 170 (2007/10/03)
Oxidation of 2-cyanoethanol, a relatively inert primary alcohol, with several systems (both homogeneous and heterogenized) based on transition metal complexes was studied. The oxidation was performed under homogeneous conditions with 35% hydrogen peroxide upon catalysis by the chlorides FeCl3 or OsCl3. The best result was obtained upon the oxidation catalyzed by OsCl3 at 70°C for 3 h in the absence of solvent: the total yield of the corresponding aldehyde and cyanoacetic acid reached 90%, and the turnover number was 1500. The systems [LMnIV(O)3Mn IVL]n(X)m-oxalic acid (where L = 1,4,7-trimethyl-1,4,7-triazacyclononane) also catalyze oxidation of 2-cyanoethanol with yields of 50-70% either under homogeneous conditions (X = PF- 6, n = 1, and m = 2) or with the use of the catalyst in the heterogenized form (as insoluble heteropoly acid salt), where X = W 12SiO4- 40, n = 2, and m = 1. Nauka/Interperiodica 2006.
Synthesis, molecular modeling, and evaluation of nonphenolic indole analogs of mycophenolic acid
El-Araby, Moustafa E.,Bernacki, Ralph J.,Makara, Gergely M.,Pera, Paula J.,Anderson, Wayne K.
, p. 2867 - 2879 (2007/10/03)
Based on the promising activity of an indole-3-carboxamide derivative, a nonphenolic analog of mycophenolic acid (MPA), we report herein the synthesis of a compound containing two important features for the activity of MPA, the ring methoxy and methyl. The synthesis was accomplished using two strategies; a method dependent on stepwise building of the hexenoate side chain followed by the indolecarboxamide ring system, and a convergent route that depended on 1,3-sigmatropic rearrangement as a key step. Docking experiments on both Chinese Hamster and Human Type-II inosine monophosphate dehydrogenase (IMPDH) showed that this compound has potential binding interactions with the NAD site. The analogs showed no activity against MCF7-S, MCF7-R, or IGR-OV1 cancer cells.
