598-10-7Relevant articles and documents
Hydrolysis of Barbituric Acid Derivatives. Part 6. Hydrolysis of Spirocyclopropane- and Spiro-2'-methylcyclopropane-1',5-barbituric Acids
Mokrosz, Jerzy L.,Paluchowska, Maria H.
, p. 1391 - 1396 (1986)
The title barbiturates are hydrolysed by pyrimidine ring degradation or by cyclopropane ring opening.The cyclopropane ring decreases the hydrolytic reactivity of the pyrimidine moiety in relation to other spirobarbiturates, owing to conjugation between the cyclopropane ring and the C-4 or C-6 carbonyl group.The kinetics and the products of the alcoholysis of these barbiturates have been investigated.The influence of the cyclopropane moiety on the pKa1 values and 13C n.m.r. spectra has also been discussed.
Synthesis of Spirooxindoles from N-Arylamide Derivatives via Oxidative C(sp2)-C(sp3) Bond Formation Mediated by PhI(OMe)2 Generated in Situ
Zhen, Xiaohua,Wan, Xintong,Zhang, Wei,Li, Qiao,Zhang-Negrerie, Daisy,Du, Yunfei
, p. 890 - 894 (2019)
A class of novel spirooxindole compounds (2) were readily synthesized, in a metal-free environment, from N-arylamide derivatives (1) via intramolecular oxidative cyclization. Direct oxidative C(sp2)-C(sp3) bond formation was realized with the least-studied PhI(OMe)2 as an oxidant, formed in situ from the reaction between PhIO and MeOH.
1, 1-cyclopropane dicarboxylic acid amide compound as well as preparation method and application thereof
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Paragraph 0024; 0028; 0031, (2021/01/11)
The invention discloses a 1, 1-cyclopropane dicarboxylic acid amide compound as well as a preparation method and application thereof, and the structural formula of the 1, 1-cyclopropane dicarboxylic acid amide compound is as shown in a formula (I): in the formula (I), the structures of two substituted benzene rings are the same, the number of substituents R on each substituted benzene ring is 1-3,and the substituent R is selected from H, halogen, C1-C4 alkyl, C2-C4 ester group or C1-C3 alkoxy. The 1, 1-cyclopropane dicarboxylic acid amide compound provided by the invention is a novel compoundwith an efficient weeding effect, and provides a basis for research and development of novel herbicides.
Exploration of novel pyrrolo[2,1-f][1,2,4]triazine derivatives with improved anticancer efficacy as dual inhibitors of c-Met/VEGFR-2
Shi, Wei,Qiang, Hao,Huang, Dandan,Bi, Xinzhou,Huang, Wenlong,Qian, Hai
, p. 814 - 831 (2018/09/29)
c-Met and VEGFR-2 have attracted interest as novel targets for treatment of various cancers. Aiming to develop potent dual c-Met and VEGFR-2 inhibitors, a series of pyrrolo[1,2-f][1,2,4]triazine derivatives were designed and synthesized. The majority of target compounds exhibited potent antiproliferative effect against c-Met addictive cancer cell lines with IC50 values ranged from 1.2 to 24.6 nM, especially 27a. In-depth studies demonstrated 27a has great selectivity to c-Met and VEGFR-2, and potent inhibitory activity against them (IC50 of 2.3 ± 0.1 nM and 5.0 ± 0.5 nM). Furthermore, it also showed the highest anticancer activity with IC50 of 0.71 ± 0.16 nM (better than the positive compound) against BaF3-TPR-Met and 37.4 ± 0.311 nM (comparable to the positive compound) against HUVEC-VEGFR2, consistent with that in c-Met sensitive tumor cell lines. Subsequently, physicochemical and pharmacokinetic characterization indicated 27a has favorable druggability and pharmacokinetic properties. Further docking studies suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, also indicating that 27a was a potential candidate for cancer therapy deserving further study.
Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors
Li, Jieming,Gu, Weijie,Bi, Xinzhou,Li, Huilan,Liao, Chen,Liu, Chunxia,Huang, Wenlong,Qian, Hai
supporting information, p. 6674 - 6679 (2017/11/28)
Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing thieno[2,3-d]pyrimidine scaffold. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2 with IC50 values in nanomolar range, especially compound 12j and 12m. Based on the further enzyme assay in vitro, compound 12j was considered as the most potent one, the IC50 values of which were 25 nM and 48 nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 12j with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogues. All the results indicate that 12j is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.
Design, synthesis and biological evaluation of 4-aminopyrimidine-5-cabaldehyde oximes as dual inhibitors of c-Met and VEGFR-2
Qiang, Hao,Gu, Weijie,Huang, DanDan,Shi, Wei,Qiu, Qianqian,Dai, Yuxuan,Huang, Wenlong,Qian, Hai
supporting information, p. 3353 - 3358 (2016/07/20)
The synergistically collaboration of c-Met/HGF and VEGFR-2/VEGF leads to development of tumor angiogenesis and progression of various human cancers. Therefore, inhibiting both HGF/c-Met and VEGF/VEGFR signaling may provide a novel and effective therapeutic approach for treating patients with abroad spectrum of tumors. Toward this goal, we designed and synthesized a series of derivatives bearing 4-aminopyrimidine-5-cabaldehyde oxime scaffold as potent dual inhibitors of c-Met and VEGFR-2. The cell proliferation assay in vitro demonstrated most target compounds have inhibition potency both on c-Met and VEGFR-2 with IC50values in nanomolar range, especially compound 14i, 18a and 18b. Based on the further enzyme assay in vitro, compound 18a was considered as the most potent one, the IC50s of which were 210?nM and 170?nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 10 and 18a with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogs. All the results indicate that 18a is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.
Arene oxidation with malonoyl peroxides
Dragan, Andrei,Kubczyk, Tomasz M.,Rowley, Julian H.,Sproules, Stephen,Tomkinson, Nicholas C. O.
supporting information, p. 2618 - 2621 (2015/06/16)
Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations, and reactivity profile studies is proposed.
A convenient synthesis of cyclopropane malonyl peroxide
Terent'Ev, Alexander O.,Vil', Vera A.,Mulina, Olga M.,Pivnitsky, Kazimir K.,Nikishin, Gennady I.
, p. 345 - 345 (2015/02/19)
Cyclopropane-1,1-dicarbonyl peroxide was prepared in 85% yield by the reaction of diethyl cyclopropane-1,1-dicarboxylate with the urea hydrogen peroxide clathrate in the presence of methanesulfonic acid.
Synthesis, crystal structure and bioactivity of N-(5-propyl-1,3,4- thiadiazol-2-yl)cyclopropanecarboxamide
Sun, Na-Bo,Jin, Jian-Zhong,Lei, Chao,He, Fang-Yue
, p. 7820 - 7822 (2013/09/23)
A new 1,3,4-thiadiazole compound with m.f. C9H 13N3OS, has been synthesized and confirmed by 1H NMR and HRMS. The single crystal structure of the 1,3,4-thiadiazole compound was determined by a single crystal X-ray diffraction study. The crystal belongs to the triclinic system, space group P-1 with a = 10.238(2), b = 10.325(2), c = 10.560(2) ?, α = 104.09(3), β = 109.50(3), γ = 93.40(3)°, Z = 4, V = 1008.4(3)?3, Mr = 211.28, Dc = 1.392 g/cm3, S = 0.98, μ = 0.29 mm-1, F(000) = 448, the final R1 = 0.0970 and wR2 = 0.2147 for 1776 were observed with I > 2Σ(I). X-ray indicated that two intermolecular hydrogen bonds N1-H1···N5, N4-H4···N2 were observed. The preliminary biological test shown that the synthesized compound has moderate herbicidal activity against Brassica campestris.
Synthesis, crystal structure and biological activity of N-(5-(o-tolyl)-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamide
Tong, Jian-Ying,Sun, Na-Bo,Wu, Hong-Ke,Liu, Xing-Hai
, p. 1349 - 1353 (2014/01/06)
A new 1, 3, 4-thiadiazole compound, N-(5-(o-tolyl)-1,3,4-thiadiazol-2-yl) cyclopropanecarboxamide, was synthesized and its structure was confirmed by 1H NMR, MS and HRMS. The single crystal structure of the title compound was determined by X-ray diffraction. The preliminary biological test showed that the synthesized compound has moderate herbicidal activity against Brassica campestris and fungicidal activities against Sclerotinia sclerotiorum(Lib.) de Bary, Rhizoctonia solanii, Fusarium oxysporum, Corynespora cassiicola, and Botrytis cinerea.
