- Direct synthesis of quinazolinones via the carbon-supported acid-catalyzed cascade reaction of isatoic anhydrides with amides and aldehydes
-
A novel catalytic system is reported for the construction of quinazolinones via the carbon-supported acid-catalyzed cascade coupling of isatoic anhydrides with amides and aldehydes. Subsequent selective hydrosilylation of the quinazolinones using a hydrogen-transfer strategy was also explored to provide dihydroquinazolines with structural diversity. The developed methodology proceeds with a broad substrate scope, excellent functional group tolerance, and utilizes a reusable catalyst and air as a green oxidant.
- Zhang, Xiangyu,Luo, Chujun,Chen, Xiaoyong,Ma, Weilin,Li, Bin,Lin, Zirui,Chen, Xiuwen,Li, Yibiao,Xie, Feng
-
-
- Discovery and antitumor activity of Benzo[d]imidazol-containing 2,4-diarylaminopyrimidine analogues as ALK inhibitors with mutation-combating effects
-
To address drug resistance caused by ALK kinase mutations, a series of novel 2,4-diarylaminopyrimidine (DAAP) analogues were designed by incorporating 1H-benzo[d]imidazol motif onto the maternal framework. All compounds were efficiently synthesized and an
- Li, Zheng,Guo, Ming,Cao, Meng,Zhao, Tianming,Li, Mingzhu,Zhai, Xin
-
-
- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
-
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
- Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
-
supporting information
p. 8297 - 8302
(2021/03/01)
-
- Design, synthesis, biological activities and 3D-QSAR studies of quinazolinone derivatives containing hydrazone structural units
-
In this study, three series of quinazolinone derivatives containing hydrazone structures were designed and synthesized. Bioactivity assays indicated that these compounds showed good antitumour activities towards human lung cancer cells (A549) and human pr
- Shao, Li-Hui,Fan, Si-Li,Meng, Ying-Fen,Gan, Yi-Yuan,Shao, Wu-Bin,Wang, Zhen-Chao,Chen, Dan-Ping,Ouyang, Gui-Ping
-
p. 4626 - 4631
(2021/03/22)
-
- Palladium-catalyzed synthesis of novel trifluoromethylated quinazolinone, N-arylquinazoline and N-benzylquinazoline derivatives
-
A simple and palladium-catalyzed procedure for synthesis of a novel series of potentially biologically active trifluoromethyl-substituted quinazolinones and N-arylquinazoline derivatives via condensation-cyclization reaction of 2-aminobenzamide, 2-amino-N′-arylbenzimidamides and 2-amino-N′-benzylbenzimidamides with trifluoroacetimidoyl chlorides has been developed. noteworthy, this investigation showed the possible of transition-metal-catalyzed activation of trifluoroacetimidoyl chlorides as a carbon trifluoromethylated source for the synthesis of quinazolines and quinazolinone derivatives in good to excellent yields.
- Sajadi, Mahdieh Sadat,Kazemi, Elham,Darehkordi, Ali
-
supporting information
(2021/04/23)
-
- Electrochemical utilization of methanol and methanol-d4 as a C1 source to access (deuterated) 2,3-dihydroquinazolin-4(1H)-one
-
Herein, an electrocatalytic protocol for the synthesis of 2,3-dihydroquinazolin-4(1H)-one has been disclosed. Methanol is activated and utilized as the C1 source to cyclize with 2-aminobenzamides. This cyclization reaction proceeds conveniently (room temperature and air atmosphere) without any homogeneous metal catalysts, external oxidants, or bases. A wide variety of N,N-disubstituted 2,3-dihydroquinazolin-4(1H)-ones are obtained via this approach. Moreover, when methanol-d4 is used, a deuterated methylene motif is incorporated into the N-heterocycles, providing an efficient approach to the deuterated N-heterocycles.
- Liu, Mingzhu,Wei, Yu,Xu, Liang
-
supporting information
(2021/10/06)
-
- Green synthesis of novel phosphonate derivatives using ultrasonic irradiation
-
[Figure not available: see fulltext.] A novel and efficient procedure for the generation of quinazolinone phosphonate derivatives employing the reaction of euparin, isatin or its derivatives, primary amines, dialkyl acetylenedicarboxylates, trimethyl phosphite or triphenyl phosphite, and acidic solution of hydrogen peroxide in aqueous media at ambient temperature under ultrasonic irradiation was developed. Without ultrasonic irradiation, the reaction does not proceed and agitation of the reaction mixture is difficult. Some advantages of this procedure are: short time of reaction, high yields of products, easy isolation of products.
- Sharafian, Shirin,Hossaini, Zinatossadat,Rostami-Charati, Faramarz,Khalilzadeh, Mohammad A.
-
p. 1283 - 1291
(2020/11/19)
-
- Aminodithioformate compound used as FAK inhibitor
-
A purpose of the invention is to provide an aminodithioformate compound serving as an FAK inhibitor, a pharmaceutical composition, a preparation method and applications thereof, wherein the compound has a structure represented by the following general formula (I).
- -
-
-
- Aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative as well as preparation and application of 2, 4-diarylaminopyrimidine derivative
-
The invention relates to an aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative represented by a general formula I, an optical isomer, a pharmaceutically acceptable salt, a solvate or a prodrug thereof, preparation methods of the aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative and the optical isomer, the pharmaceutically acceptable salt, the solvate or the prodrug, and a pharmaceutical composition using the compound represented by the general formula I as an active component, wherein substituents R1, R2, R3, R4, R5, R6, X, Y and Z have meanings given inthe specification. The invention also relates to the compound shown in the general formula I, which has strong ALK and ROS1 kinase inhibition effects, and also relates to application of the compound and the optical isomer and pharmaceutically acceptable salt thereof in preparation of drugs for treatment and/or prevention of diseases caused by ALK and ROS1 abnormal expression, and application of the compound in preparation of drugs for prevention of diseases caused by ALK and ROS1 abnormal expression. Use in particular in the preparation of a medicament for treatment and/or for preventing cancer
- -
-
Paragraph 0322-0324
(2020/08/18)
-
- Design and synthesis of diphenylpyrimidine derivatives (DPPYs) as potential dual EGFR T790M and FAK inhibitors against a diverse range of cancer cell lines
-
A new class of pyrimidine derivatives were designed and synthesized as potential dual FAK and EGFRT790M inhibitors using a fragment-based drug design strategy. This effort led to the identification of the two most active inhibitors, namely 9a and 9f, against both FAK (IC50 = 1.03 and 3.05 nM, respectively) and EGFRT790M (IC50 = 3.89 and 7.13 nM, respectively) kinase activity. Moreover, most of these compounds also exhibited strong antiproliferative activity against the three evaluated FAK-overexpressing pancreatic cancer (PC) cells (AsPC-1, BxPC-3, Panc-1) and two drug-resistant cancer cell lines (breast cancer MCF-7/adr cells and lung cancer H1975 cells) at concentrations lower than 6.936 μM. In addition, 9a was also effective in the in vivo assessment conducted in a FAK-driven human AsPC-1 cell xenograft mouse model. Overall, this study offers a new insight into the treatment of hard to treat cancers.
- Ai, Min,Wang, Changyuan,Tang, Zeyao,Liu, Kexin,Sun, Xiuli,Ma, Tengyue,Li, Yanxia,Ma, Xiaodong,Li, Lei,Chen, Lixue
-
-
- Discovery of 7H-pyrrolo[2,3-d]pyridine derivatives as potent FAK inhibitors: Design, synthesis, biological evaluation and molecular docking study
-
Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase responsible for development of various tumor types. Aiming to explore new potent inhibitors, two series of 2,4-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized on the base of structure-based design strategy. Biological evaluation indicated that most of these new compounds could potently inhibit FAK kinase, leading to the promising inhibitors against the proliferation of U-87MG, A-549, and MDA-MB-231 cancer cell lines. Among them, the optimized compound 18h potently inhibited the enzyme (IC50 = 19.1 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC50 values of 0.35, 0.24, and 0.34 μM, respectively. Compound 18h is a multi-target kinase inhibitor. Furthermore, compound 18h also exhibited relatively less cytotoxicity (IC50 = 3.72 μM) toward a normal human cell line, HK2. According to the flow cytometry and wound healing assay results, compound 18h effectively induced apoptosis and G0/G1 phase arrest of MDA-MB-231 cells and suppressed the migration of U-87MG, A-549 and MDA-MB-231 cells. The docking study of compound 18h was performed to elucidate its possible binding modes and to provide a structural basis for the further structural guidance design of FAK inhibitors. Collectively, these data support the further development of compound 18h as a lead compound for FAK-targeted anticancer drug discovery.
- Wang, Ruifeng,Zhao, Xiangxin,Yu, Sijia,Chen, Yixuan,Cui, Hengxian,Wu, Tianxiao,Hao, Chenzhou,Zhao, Dongmei,Cheng, Maosheng
-
-
- Quinazolinone compound containing hydrazone structural unit or stereoisomer, salt or solvate of the quinazolinone compound
-
The invention relates to a quinazolinone compound containing a hydrazone structural unit, or a stereoisomer, or a salt or a solvate of the quinazolinone compound. The compound has a structure as shownin a general formula (I) shown in the specification. Th
- -
-
Paragraph 0041-0043
(2020/07/08)
-
- Design, synthesis and in vitro biological evaluation of quinazolinone derivatives as EGFR inhibitors for antitumor treatment
-
In this paper, a series of novel 3-methyl-quinazolinone derivatives was designed, synthesised and evaluated for antitumor activity in vitro on wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) and three human cancer cell li
- Fu, Yihong,Gan, Yiyuan,Le, Yi,Li, Wen,Liu, Jiamin,Ouyang, Guiping,Wang, Zhenchao,Yan, Longjia,Zhou, Zhixu,Zou, Xue
-
p. 555 - 564
(2020/02/11)
-
- Pyrroformyl-containing 2,4-diaminopyrimidine derivatives as a new optimization strategy of ALK inhibitors combating mutations
-
Aiming to identify new optimization strategy effective for ALK-mutations, two series of pyrroformyl-containing 2,4-diaminopyrimidine compounds (11a-o, 12a-o) were designed, synthesized and evaluated for their anti-proliferative activities against three ca
- Cao, Meng,Chen, Yuxiang,Guo, Ming,Wei, Shangfei,Zhai, Xin,Zhao, Tianming
-
-
- Synthesis method of 2-amino-3, 5-dichloro-N-methylbenzamide
-
The invention relates to a synthesis method of 2-amino-3, 5-dichloro-N-methylbenzamide, which comprises the following steps: 1) adding isatoic anhydride into a solvent A, dropwisely adding a methylamine solution to react, adding water, uniformly stirring,
- -
-
Paragraph 0047-0048; 0051-0052; 0055-0056
(2021/01/11)
-
- Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells
-
A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC50 = 5.17 nM) and 7f (IC50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). In particular, compound 7a also exhibited strong antiproliferative activity against several stubborn cancer cells, including AsPC-1 cells (IC50 = 0.105 μM), BxPC-3 cells (IC50 = 0.090 μM), and MCF-7/ADR cells (IC50 = 0.59 μM). Additionally, compound 7a also showed great antitumor efficacy in vivo via aAsPC-1 cancer Xenograft mouse model. The preliminary mechanism study by Western blot analysis revealed that 7a repressed FAK phosphorylation in AsPC cancer cells. Taken together, the results indicate that compound 7a may serve as a promising preclinical candidate for treatment of stubborn cancers.
- Wang, Luhong,Ai, Min,Yu, Jiawen,Jin, Lingling,Wang, Changyuan,Liu, Zhihao,Shu, Xiaohong,Tang, Zeyao,Liu, Kexin,Luo, Hui,Guan, Wenshun,Sun, Xiuli,Ma, Xiaodong
-
p. 154 - 162
(2019/04/13)
-
- Discovery of 2,4-diarylaminopyrimidine derivatives bearing dithiocarbamate moiety as novel FAK inhibitors with antitumor and anti-angiogenesis activities
-
A series of 2,4-diarylaminopyrimidine derivatives containing dithiocarbamate moiety were designed by molecular hybridization strategy and synthesized for screening as inhibitors of focal adhesion kinase (FAK). Most of these compounds exhibit significant a
- Su, Yue,Li, Ridong,Ning, Xianling,Lin, Zhiqiang,Zhao, Xuyang,Zhou, Juntuo,Liu, Jia,Jin, Yan,Yin, Yuxin
-
-
- Focal adhesion kinase inhibitor and use
-
The invention belongs to the field of medicines, relates to a focal adhesion kinase inhibitor and use, in particular relates to a novel focal adhesion kinase inhibitor compound, or stereoisomers, geometric isomers, tautomers, oxynitrides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, further relates to the use of the compound and pharmaceutical compositions as medicines, in particular the use of the compound and pharmaceutical compositions in manufacture of medicines for treatment or prevention of cancer, pulmonary hypertension, and pathological angiogenesis-related diseases.
- -
-
Paragraph 0435; 0437; 0438
(2019/01/08)
-
- Design, synthesis and insecticidal activity of diamides with oxydibenzene or diphenylamine subunits
-
Introduction: After using insecticides over many years, the resistance and environmental issues have become great challenges to crop protection. Modern agriculture calls for new insecticidal candidates. Phthalic diamide insecticide containing adjacent two amide group were favored for its new mode of action. Most chemical optimizations of phthalic diamide insecticide focused on amide groups. Modifications on phenyl part including fewer substituent types. Objective: The objective of this article was to investigate the insecticidal activities variation by alter the orientation and distance of two amide by replace the phenyl part with oxydibenzene and diphenyl-amine. Results: The target compounds were synthesized by using Cu/CuI catalyzed Ullmann coupling and sulfonyl-O-acryl mixed-anhydride as reactive intermediate. All target compounds were evaluated against armyworm (Mythimna sepatara). Two of synthetic compounds containing multifluoro-alkoxyl substituent showed mortality rate of 100% at 500 mg L-1. DFT-based Potential energy surface scanning showed that the relative energies of three conformations of insecticidal compounds were very similar Conclusion: We designed, synthesized and characterized seventeen novel compounds for the insecticidal candidates. Two of them were found to be insecticidal. A preliminary structure-activity relationship showed that the multifluoro-alkoxyl groups on the benzene were preferred. The compound d5 could be a lead compound for further research.
- Liu, Ye,Chen, Xinfei,Xu, Xiaoyong,Cheng, Jiagao,Shao, Xusheng,Li, Zhong
-
p. 262 - 269
(2017/02/15)
-
- Diversification of quinazolinones by Pd-catalyzed C(sp3)-acetoxylation
-
The quinazolinone ring has been exploited as a directing group for C(sp3)-H functionalization for the first time. The proximal C-γ(sp3)-H bonds have been oxidized by palladium-catalyzed acetoxylation reaction. Various functional grou
- Garad, Dnyaneshwar N.,Mhaske, Santosh B.
-
p. 10470 - 10478
(2018/05/31)
-
- Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity
-
A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100?nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10?μM, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells). Results of flow cytometry indicated that inhibitor 7e promoted apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, it almost completely induced the apoptosis at a concentration of 10?μM. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer.
- Qu, Menghua,Liu, Zhihao,Zhao, Dan,Wang, Changyuan,Zhang, Jianbin,Tang, Zeyao,Liu, Kexin,Shu, Xiaohong,Yuan, Hong,Ma, Xiaodong
-
p. 3989 - 3996
(2017/07/05)
-
- Phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with enhanced activity against pancreatic cancer cell lines
-
A family of phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) were synthesized as potent focal adhesion kinase (FAK) inhibitors. The PA-DPPY derivatives could significantly inhibit the FAK enzymatic activity at concentrations lower than 10.69 nM. Among them, compounds 7a and 7e were two of the most active FAK inhibitors, possessing IC50 values of 4.25 nM and 4.65 nM, respectively. In particular, compound 7e also displayed strong activity against AsPC cell line, with an IC50 of 1.66 μM, but show low activity against the normal HPDE6-C7 cells (IC50 > 20 μM), indicating its low cell cytotoxicity. Additionally, flow cytometry analysis showed that after treatment with 7e (8 μM, 72 h), both AsPC and Panc cells growth were almost totally inhibited, with a cell viability rate of 16.8% and 18.1%, respectively. Overall, compound 7e may be served as a valuable FAK inhibitor for the treatment of pancreatic cancer.
- Liu, He,Wu, Bin,Ge, Yang,Huang, Jiaxin,Song, Shijie,Wang, Changyuan,Yao, Jihong,Liu, Kexin,Li, Yanxia,Li, Yongming,Ma, Xiaodong
-
p. 6313 - 6321
(2017/11/16)
-
- Novel pyrimidine anti-tumor compound and preparation method and application thereof
-
The invention relates to a novel pyrimidine anti-tumor compound and a preparation method and application thereof. The novel pyrimidine anti-tumor compound is a compound shown in a formula (I), wherein each substituted group in the formula (I) is defined in the description. The invention also relates to the compound shown in the formula (I) or a pharmaceutically acceptable salt thereof, or application of a medicine composition containing the compound in inhibiting focal adhesion kinase, further treating tumor diseases, and especially treating pancreatic cancers, lung cancers and breast cancers. The formula (I) is shown in the description.
- -
-
Paragraph 0084; 0085; 0089; 0090; 0091
(2017/10/22)
-
- Development of a Process Route to the FAK/ALK Dual Inhibitor TEV-37440
-
The development of a scalable route to TEV-37440, a dual inhibitor of focal adhesion kinase (FAK) and anaplastic lymphoma kinase (ALK), is presented. The medicinal chemistry route used to support this target through nomination is reviewed, along with the
- Allwein, Shawn P.,Mowrey, Dale R.,Petrillo, Daniel E.,Reif, James J.,Purohit, Vikram C.,Milkiewicz, Karen L.,Bakale, Roger P.,Christie, Michael A.,Olsen, Mark A.,Neville, Christopher J.,Gilmartin, Gregory J.
-
p. 740 - 747
(2017/06/05)
-
- OXAZINE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
-
PROBLEM TO BE SOLVED: To provide a compound that specifically inhibits the signal transmission of an IL-23 receptor uncompetitively with IL-23 without inhibiting phosphoenzyme activity of janus kinases. SOLUTION: The present invention provides an oxazine derivative represented by the following formula or a pharmacologically acceptable salt thereof. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0094; 0095; 0096
(2016/10/07)
-
- Mechanistic insights into a catalyst-free method to construct quinazolinones through multiple oxidative cyclization
-
A novel one-pot benign oxidative cyclization of alcohols with 2-aminobenzamides was successfully developed without catalyst to afford the quinazolinones under O2. This one-pot protocol involved oxidations and cyclizations to construct the skeleton of quinazolinones through possibly three kinds of distinct reaction mechanisms.
- Wang, Zhen-Zhen,Tang, Yu
-
p. 1330 - 1336
(2017/02/15)
-
- Experimental and theoretical investigations into the stability of cyclic aminals
-
Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking. Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pKa values of the N-3 nitrogen atom. Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account.
- Sawatzky, Edgar,Drakopoulos, Antonios,R?lz, Martin,Sotriffer, Christoph,Engels, Bernd,Decker, Michael
-
supporting information
p. 2280 - 2292
(2016/11/17)
-
- 3,5-dihalogenated thiophosphoro benzamides insecticide
-
The invention discloses a 3,5-dihalogenation sulfo-benzamide insecticide and preparation method and application thereof. The 3,5-dihalogenation sulfo-benzamide insecticide is represented as a structural formula I. In the formula I: R1 is C1 or Br, R2 is selected from methyl, isopropyl and allyl, and R3 is H or C1. The 3,5-dihalogenation sulfo-benzamide insecticide can be used for prevention and control of agricultural insects or forest insects.
- -
-
Paragraph 0025; 0026; 0027; 0028
(2017/04/22)
-
- An integrated flow and microwave approach to a broad spectrum protein kinase inhibitor
-
The protein kinase inhibitor CTx-0152960 (6, 2-((5-chloro-2-((4-morpholinophenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide), and the piperazinyl analogue, CTx-0294885 (7, 2-((5-chloro-2-((4-piperazin-1-ylphenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide), were prepared using a hybrid flow and microwave approach. The use of flow chemistry approaches avoided the need for Boc-protection of piperidine in the key SNAr coupling with 1-fluoro-4-nitrobenzene. Microwave coupling of 4-morphilinoaniline 8 and 4-(piperazine-1-yl)aniline 9 with 2-(2,5-dichloropyrimidine-4-ylamino)-N-methylbenzamide 10, proved to be the most efficacious route to the target analogues 6 and 7. This hybrid methodology reduced the number of synthetic steps, gave enhanced overall yields and increased atom economy through step reduction and minimal requirement for chromatographic purification, relative to the original batch synthesis approach.
- Russell, Cecilia,Lin, Andrew J. S.,Hains, Peter,Simone, Michela I.,Robinson, Phillip J.,Mccluskey, Adam
-
p. 93433 - 93437
(2015/11/17)
-
- Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives targeting calcium channel
-
A series of compounds containing dihydroquinazolinone moiety was designed and synthesized. Amine bridge part was changed in comparison with known anthranilic diamides insecticides. Their insecticidal activities against oriental armyworm (Mythimna separata) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compounds 5a and 5k showed 80% larvicidal activities against oriental armyworm at the concentration of 5 mg/L. The present study also explored the possible effects of target compounds on the high voltage-gated calcium channel and the calcium channels in the endoplasmic reticulum in the central neurons isolated from the third instar larvae of Spodoptera exigua using whole-cell patch clamp and calcium imaging technique. The results showed that compound 5a activated the high voltage-gated calcium channel in the central neurons of S. exigua weakly. The peak currents only increased by 6% of the initial value at the end of the 10-min recording after treated with 0.22 μM 5a, while chlorantraniliprole has an opposite effect. The effects of 5a on the intracellular calcium ion concentration ([Ca2+]i) in neurons were well investigated. The experimental results indicated that these novel compounds have different mechanism compared with chlorantraniliprole.
- Zhou, Yunyun,Feng, Qi,Di, Fengjuan,Liu, Qiaoxiao,Wang, Duoyi,Chen, Youwei,Xiong, Lixia,Song, Haibin,Li, Yuxin,Li, Zhengming
-
p. 4968 - 4975
(2013/09/02)
-
- PYRAZOLE AMIDE COMPOUNDS AND USES THEREOF
-
Disclosed is a pyrazole amide compound having fungicidal activity, with a structure shown by the general formula (I): Each of the substituents of the compound being defined as in the description. The compound of the present invention has fungicidal activity, and excellent prevention and controlling effects on diseases, such as cucumber downy mildew, corn rust, wheat powdery mildew, rice blast, etc., and in particular, a better prevention and controlling effect on cucumber downy mildew and corn rust. Also disclosed is a process for preparing the compound, a fungicidal composition containing the compound of general formula (I) and the use thereof in preventing and controlling disease in crops.
- -
-
-
- PYRAZOLE AMIDE COMPOUND AND USE THEREOF
-
Disclosed is a pyrazole amide compound having fungicidal activity, with a structure shown by the general formula (I): Each of the substituents of the compound being defined as in the description. The compound of the present invention has fungicidal activity, and excellent prevention and controlling effects on diseases, such as cucumber downy mildew, corn rust, wheat powdery mildew, rice blast, etc., and in particular, a better prevention and controlling effect on cucumber downy mildew and corn rust. Also disclosed is a process for preparing the compound, a fungicidal composition containing the compound of general formula(I) and the use thereof in preventing and controlling disease in crops.
- -
-
-
- BINDING AGENT
-
The present disclosure generally relates to protein binding agents, such as protein kinase binding agents of general Formula (I). The protein binding agents may be provided attached to a solid support and may be used, for example, to detect the presence o
- -
-
Page/Page column 29
(2013/06/06)
-
- A one-pot transition-metal-free tandem process to 1,4-benzodiazepine scaffolds
-
An efficient and practical method for the synthesis of 1,4-benzodiazepines is reported. This methodology offers a transition-metal-free tandem process in one pot. This process is applicable to the construction of a wide variety of 1,4-benzodiazepines and other tricyclic systems with high potential biological and pharmacological activities. Georg Thieme Verlag Stuttgart · New York.
- Li, Yanqiu,Zhan, Chunjing,Yang, Bingchuan,Cao, Xiaoqun,Ma, Chen
-
p. 111 - 117
(2013/03/13)
-
- One-pot synthesis of quinazolinones from anthranilamides and aldehydes via p -toluenesulfonic acid catalyzed cyclocondensation and phenyliodine diacetate mediated oxidative dehydrogenation
-
A variety of 4(3H)-quinazolinones are synthesized conveniently in one pot from 2-aminobenzamides and aldehydes, via cyclization catalyzed by p-toluenesulfonic acid followed by oxidative dehydrogenation mediated by the hypervalent iodine compound phenyliodine diacetate [PhI(OAc)2, PIDA]. Highlights of the described method include the first synthesis of quinazolinones bearing an N-alkoxy substituent, a new application of phenyliodine diacetate as an efficient dehydrogenative oxidant, and mild reaction conditions. Georg Thieme Verlag Stuttgart, New York.
- Cheng, Ran,Guo, Tianjian,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
-
p. 2998 - 3006
(2013/11/06)
-
- Three-component (Domino) reaction affording substituted pyrroloquinazolines: Cyclization regioselectivity and stereoselectivity
-
The cyclization involving 2-(aminomethyl)aniline, methyl 3,3,3-trifluoropyruvate, and various oxo compound afforded linearly annulated pyrroloquinazolines, for example, (2R,3aS)-2-hydroxy-3a-phenyl-2- trifluoromethyl-3,3a,4,9-tetrahydropyrrolo[2,1-b]quina
- Paleta, Oldrich,Dolensky, Bohumil,Palecek, Jiri,Kvicala, Jaroslav
-
supporting information
p. 1262 - 1270
(2013/04/10)
-
- 2,4-DIAMINO-6,7-DIHYDRO-5H-PYRROLO[2,3]PYRIMIDINE DERIVATIVES AS FAK/Pyk2 INHIBITORS
-
The invention relates to a novel class of 2,4-diamino-6,7-dihydro-5H-pyrrolo[2,3]pyrimidine derivatives as a FAK and/or Pyk2 inhibitor, to a process for their preparation, and to a composition thereof, as well as to use of the compounds for the inhibiting FAK and/or Pyk2 and method for the treatment of a FAK and/ or Pyk2 mediated disorder or disease.
- -
-
Page/Page column 61
(2012/07/27)
-
- Two-directional approach for the rapid synthesis of 2,4-bis-aminoaryl pyridine derivatives
-
We have developed two different approaches in parallel to rapidly access 2,4-bis aminoaryl pyridine compounds from a common starting material. The C-4/C-2 approach uses palladium-mediated coupling reactions to sequentially functionalize C-4 and then C-2. An alternative C-2/C-4 route uses a regioselective SNAr reaction to first substitute at C-2 then subsequently at C-4 by a palladium-mediated reaction. Both approaches have been used successfully to provide a range of 2,4-bis-aminoaryl pyridine compounds.
- Morgentin, Remy,Barlaam, Bernard,Foote, Kevin,Hassall, Lorraine,Hawkins, Janet,Jones, Clifford D.,Le Griffon, Antoine,Peru, Aurelien,Ple, Patrick
-
experimental part
p. 8 - 24
(2011/10/18)
-
- Fused bicyclic derivatives of 2,4-diaminopyrimidine as c-Met inhibitors
-
The HGF-c-Met signaling axis is an important paracrine mediator of epithelial-mesenchymal cell interactions involving the regulation of multiple cellular activities including cell motility, mitogenesis, morphogenesis, and angiogenesis. Dysregulation of c-Met signaling (e.g., overexpression or increased activation) is associated with the development of a wide range of tumor types; thus, inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of a 2-arylaminopyrimidine scaffold led to a series of potent c-Met inhibitors bearing a C4-2-amino-N-methylbenzamide group. Specifically, a series of C2-benzazepinone analogs demonstrated potent inhibition of c-Met in enzymatic and cellular assays. Kinase selectivity could be tuned by varying the nature of the alkyl group on the benzazepinone nitrogen.
- Weinberg, Linda R.,Albom, Mark S.,Angeles, Thelma S.,Husten, Jean,Lisko, Joseph G.,McHugh, Robert J.,Milkiewicz, Karen L.,Murthy, Seetha,Ott, Gregory R.,Theroff, Jay P.,Tripathy, Rabindranath,Underiner, Ted L.,Zificsak, Craig A.,Dorsey, Bruce D.
-
supporting information; experimental part
p. 164 - 167
(2011/03/17)
-
- COMPOUNDS THAT MODULATE EGFR ACTIVITY AND METHODS FOR TREATING OR PREVENTING CONDITIONS THEREWITH
-
Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith.
- -
-
Page/Page column 41
(2011/11/30)
-
- 2,4-Diaminopyrimidine inhibitors of c-Met kinase bearing benzoxazepine anilines
-
Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lead opt
- Zificsak, Craig A.,Theroff, Jay P.,Aimone, Lisa D.,Albom, Mark S.,Angeles, Thelma S.,Brown, Rebecca A.,Galinis, Deborah,Grobelny, Jennifer V.,Herbertz, Torsten,Husten, Jean,Kocsis, Laura S.,Losardo, Christine,Miknyoczki, Sheila J.,Murthy, Seetha,Rolon-Steele, Damaris,Underiner, Ted L.,Wells-Knecht, Kevin J.,Worrell, Candace S.,Zeigler, Kelli S.,Dorsey, Bruce D.
-
scheme or table
p. 660 - 663
(2011/03/18)
-
- Synthesis of 2,3-dihydroquinazolin-4(1H)-ones by three-component coupling of isatoic anhydride, amines, and aldehydes catalyzed by magnetic Fe 3O4 nanoparticles in water
-
A simple and efficient protocol for one-pot three-component coupling of isatoic anhydride, amines, and aldehydes in water using magnetically recoverable Fe3O4 nanoparticles is reported. This methodology results in the synthesis of a variety of 2,3-dihydroquinazolin-4(1H)-ones in high yields. The catalyst can be recovered and recycled without a significant loss in the catalytic activity.
- Zhang, Zhan-Hui,Lue, Hong-Yan,Yang, Shu-Hong,Gao, Jian-Wu
-
experimental part
p. 643 - 646
(2010/10/20)
-
- Development of novel 2-[4-(aminoalkoxy)phenyl]-4(3H)-quinazolinone derivatives as potent and selective histamine H3 receptor inverse agonists
-
Novel 2-[4-(aminoalkoxy)phenyl]-4(3H)-quinazolinone derivatives were identified as potent human H3 receptor inverse agonists. After systematic modification of lead 5a, the potent and selective analog 5r was identified. Elimination of hERG K+ channel and human α1A-adrenoceptor activities is the main focus of the present study.
- Mizutani, Takashi,Nagase, Tsuyoshi,Ito, Sayaka,Miyamoto, Yasuhisa,Tanaka, Takeshi,Takenaga, Norihiro,Tokita, Shigeru,Sato, Nagaaki
-
scheme or table
p. 6041 - 6045
(2009/06/30)
-
- PROCESS FOR THE PREPARATION OF ANTHRANILAMIDE DERIVATIVES
-
The present invention relates to a process for the preparation of a compound of formula (I), by a) treating a compound of formula (Il), with a compound of formula (III), in the presence of a base to form a compound of formula (IV), and b) converting said
- -
-
Page/Page column 79-80
(2010/11/30)
-
- Cyclization of 2-benzoylamino-N-methyl-thiobenzamides to 3-methyl-2-phenylquinazolin-4-thiones
-
Acylation of 2-amino-N-methyl-thiobenzamide with substituted benzoyl chlorides has been used to synthesize the corresponding 2-benzoylamino-N- methylthiobenzamides. Subsequent sodium methoxide-catalyzed ring closure gives the corresponding 3-methyl-2-phen
- Hanusek, Jiri,Rosa, Pavel,Drabina, Pavel,Sedlak, Milos
-
p. 1281 - 1285
(2007/10/03)
-
- 2, 4- DI (PHENYLAMINO) PYRIMIDINES USEFUL IN THE TREATMENT OF NEOPLASTIC DISEASES, INFLAMMATORY AND IMMUNE SYSTEM DISORDERS
-
Novel pyrimidine derivatives of formula (I), to processes for their production, their use as pharmaceuticals in the treatment of neoplastic diseases, inflammatory and immune system disorders and to pharmaceutical compositions comprising them.
- -
-
Page 110-111
(2010/02/08)
-
- Synthesis and reactions of some 2-Vinyl-3H-quinazolin-4-ones
-
A simple, high-yielding synthesis of 2-vinyl-3H-quinazolin-4-one, 2-(1-chlorovinyl)-3H-quinazolin-4-one and 2-(1-bromovinyl)-3H-quinazolin-4-one. The 2-vinylquinazolinones 11a and 14 participate readily in nucleophilic addition reactions. Treatment with both carbon and nitrogen nucleophiles results in a clean conversion into a variety of 2-substituted 3H-quinazolin-4-one derivatives. The 2-(1-halovinyl)-3H-quinazolin-4-ones 11b and 11c reacted with carbon nucleophiles to give several derivatives of 2-substituted 3H-quinazolin-4-one, such as dihydrofurancarboxylic ethyl ester 23. (C) 2000 Elsevier Science Ltd.
- Witt, Anette,Bergman, Jan
-
p. 7245 - 7253
(2007/10/03)
-
- Synthesis and pharmacological activity of triazole derivatives inhibiting eosinophilia
-
In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1- [(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the airway through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1- [(methylamino)(thiocarbonyl)]-1H-triazole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally (ip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD50 value of >2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D4 (LTD4) or platelet-activating factor (PAF)- induced responses. Taken together, these results suggest 23c as a novel candidate for the treatment of chronic asthma. Further studies are now underway.
- Naito, Youichiro,Akahoshi, Fumihiko,Takeda, Shinji,Okada, Takehiro,Kajii, Masahiko,Nishimura, Hiroko,Sugiura, Masanori,Fukaya, Chikara,Kagitani, Yoshio
-
p. 3019 - 3029
(2007/10/03)
-