- Photo-Triggered Self-Induced Homolytic Dechlorinative Sulfonylation/Cyclization of Unactivated Alkenes: Synthesis of Quinazolinones Containing a Sulfonyl Group
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A self-photocatalyzed sulfonylation/cyclization of quinazolinones containing unactivated alkenes with various sulfonyl chlorides was developed. The protocol provides access to sulfonyl radicals via energy transfer from the quinazolinone skeleton to the sulfonyl chloride. Notably, the transformations proceeded without any external photocatalysts, additives, or oxidants, providing an alternative method for fabricating sulfonylated compounds.
- Sun, Bin,Ding, Hao,Tian, Hai-Xia,Huang, Pan-Yi,Jin, Can,Wu, Chun-Lei,Shen, Run-Pu
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supporting information
p. 766 - 772
(2021/12/22)
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- Electrosynthesis of CF3-Substituted Polycyclic Quinazolinones via Cascade Trifluoromethylation/Cyclization of Unactivated Alkene
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An atom and step economy cascade trifluoromethylation/cyclization of unactivated alkene with Langlois reagent as a CF3 source is described. A variety of polycyclic quinazolinones were successfully synthesized in 52–81% yields under transition metal- and oxidant-free conditions. The Langlois reagent used in this strategy as a CF3 reagent possesses the advantages of bench-stablity, cost-effectivity and high-efficiency. Additionally, gram-scale reaction, broad substrate scope and good functional group tolerance demonstrated the synthetic usefulness of this protocol.
- Liu, Lei,Zhang, Wangqin,Xu, Chao,He, Jiaying,Xu, Zhenhui,Yang, Zehui,Ling, Fei,Zhong, Weihui
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supporting information
p. 1319 - 1325
(2022/03/15)
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- Visible-Light Photosynthesis of CHF2/CClF2/CBrF2-Substituted Ring-fused Quinazolinones in Dimethyl Carbonate
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With eco-friendly and sustainable CO2-derived dimethyl carbonate as the sole solvent, the visible-light-induced cascade radical reactions have been established as a green and efficient tool for constructing various CHF2/CClF2/CBrF2-substituted ring-fused quinazolinones.
- Gui, Qing-Wen,He, Wei-Min,Huang, Wen-Jie,Lu, Zi-Qin,Ouyang, Wen-Tao,Teng, Fan,Xun, Changping,Yang, Hao,Zhu, Meng-Xue
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- Self-catalyzed phototandem perfluoroalkylation/cyclization of unactivated alkenes: Synthesis of perfluoroalkyl-substituted quinazolinones
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A novel visible-light-induced radical tandem trifluoromethylation/cyclization of unactivated alkenes with sodium perfluoroalkanesulfinates (Rf = CF3, C3F7, C4F9, C6F13, C8F17) under air atmosphere has been developed. A range of quinazolinones containing unactivated alkene moiety and sodium perfluoroalkanesulfinates were compatible with this transformation, leading to a variety of perfluoroalkyl-substituted quinazoline alkaloids. Remarkably, the experiment can be carried out without any metal catalyst, strong oxidant, or external photosensitizer.
- Sun, Bin,Huang, Panyi,Yan, Zhiyang,Shi, Xiayue,Tang, Xiaoli,Yang, Jin,Jin, Can
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supporting information
p. 1026 - 1031
(2021/02/06)
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- Photoinduced homolytic decarboxylative acylation/cyclization of unactivated alkenes with α-keto acid under external oxidant and photocatalyst free conditions: access to quinazolinone derivatives
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A novel and green strategy for the synthesis of acylated quinazolinone derivativesviaphoto-induced decarboxylative cascade radical acylation/cyclization of quinazolinone bearing unactivated alkenes has been developed. The protocol provides a novel route to access acyl radicals from α-keto acids through a self-catalyzed energy transfer process. Most importantly, the reaction proceeded smoothly without any external photocatalyst, additive or oxidant, and could be easily scaled-up in flow conditions with sunlight irradiation.
- Sun, Bin,Shi, Rongcheng,Zhang, Kesheng,Tang, Xiaoli,Shi, Xiayue,Xu, Jiayun,Yang, Jin,Jin, Can
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supporting information
p. 6050 - 6053
(2021/06/21)
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- Photo-triggered self-catalyzed fluoroalkylation/cyclization of unactivated alkenes: Synthesis of quinazolinones containing the CF2R group
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A novel photo-triggered self-catalyzed fluoroalkylation/cyclization of quinazolinones containing unactivated alkenes with various fluoroalkyl bromides has been developed. This transformation exhibits excellent substrate generality with respect to both the coupling partners. Of note is that this is the first example describing the Csp3-Br bond homolysis of alkyl bromides via a substrate (quinazolinones) induced energy transfer process. Additionally, the mild conditions, tolerance to a wide range of functional groups and operational simplicity make this protocol practical for the synthesis of fluorine-containing ring-fused quinazolinones. This journal is
- Yang, Jin,Sun, Bin,Ding, Hao,Huang, Pan-Yi,Tang, Xiao-Li,Shi, Rong-Cheng,Yan, Zhi-Yang,Yu, Chuan-Ming,Jin, Can
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supporting information
p. 575 - 581
(2021/01/28)
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- Synthesis, Anti-Tomato Spotted Wilt Virus Activities, and Interaction Mechanisms of Novel Dithioacetal Derivatives Containing a 4(3 H)-Quinazolinone Pyrimidine Ring
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A series of unreported novel dithioacetal derivatives containing a 4(3H)-quinazolinone pyrimidine ring were synthesized, and their antiviral activities were evaluated against tomato spotted wilt virus (TSWV). A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was established, and compound D32 was designed and synthesized according to the analysis results of the CoMFA and CoMSIA models. The bioassay results showed that compound D32 exhibited excellent inactivation activity against TSWV, with EC50 values of 144 μg/mL, which was better than those of ningnanmycin (149 μg/mL) and the lead compound xiangcaoliusuobingmi (525 μg/mL). The binding ability of compound D32 to TSWV CP was tested by microscale thermophoresis (MST), and the binding constant value was 4.4 μM, which was better than those of ningnanmycin (6.2 μM) and xiangcaoliusuobingmi (59.1 μM). Therefore, this study indicates that novel dithioacetal derivatives containing a 4(3H)-quinazolinone pyrimidine ring may be applied as new antiviral agents.
- Chen, Jixiang,Hu, Deyu,Song, Baoan,Zu, Guangcheng
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p. 14459 - 14466
(2021/12/06)
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- COMPOUNDS FOR THE TREATMENT OF BRAF-ASSOCIATED DISEASES AND DISORDERS
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Provided herein are compounds of the Formula I: and pharmaceutically acceptable salts, solvates and polymorphs thereof, wherein L, X1, R1, R2, R3, R4, R5 and R6 are as defined herein, for the treatment of BRAF-associated diseases and disorders, including BRAF-associated tumors, including malignant and benign BRAF-associated tumors of the CNS and malignant extracranial BRAF-associated tumors.
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Paragraph 1006; 1011; 1012
(2021/01/20)
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- Visible-light induced copper(i)-catalyzed oxidative cyclization of: O -aminobenzamides with methanol and ethanol via HAT
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The use of the in situ generated ligand-copper superoxo complex absorbing light energy to activate the alpha C(sp3)-H of MeOH and EtOH via the hydrogen atom transfer (HAT) process for the synthesis of quinazolinones by oxidative cyclization of alcohols with o-aminobenzamide has been investigated. The synthetic utility of this protocol offers an efficient synthesis of a quinazolinone intermediate for erlotinb (anti-cancer agent) and 30 examples were reported.
- Bhargava Reddy, Mandapati,Prasanth, Kesavan,Anandhan, Ramasamy
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p. 9601 - 9605
(2020/12/28)
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- Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1) Antagonists Demonstrating Potent in Vivo Activity
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There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo target coverage has been challenging. Here we describe the optimization of a potent, selective series of quinazolinone-based TRPA1 antagonists. High-throughput screening identified 4, which possessed promising potency and selectivity. A strategy focused on optimizing potency while increasing polarity in order to improve intrinisic clearance culminated with the discovery of purinone 27 (AM-0902), which is a potent, selective antagonist of TRPA1 with pharmacokinetic properties allowing for >30-fold coverage of the rat TRPA1 IC50 in vivo. Compound 27 demonstrated dose-dependent inhibition of AITC-induced flinching in rats, validating its utility as a tool for interrogating the role of TRPA1 in in vivo pain models.
- Schenkel, Laurie B.,Olivieri, Philip R.,Boezio, Alessandro A.,Deak, Holly L.,Emkey, Renee,Graceffa, Russell F.,Gunaydin, Hakan,Guzman-Perez, Angel,Lee, Josie H.,Teffera, Yohannes,Wang, Weiya,Youngblood, Beth D.,Yu, Violeta L.,Zhang, Maosheng,Gavva, Narender R.,Lehto, Sonya G.,Geuns-Meyer, Stephanie
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p. 2794 - 2809
(2016/04/10)
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- Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP-ribose)polymerase-1 inhibitors
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We have demonstrated that quinazolin-4(3H)-one, a nicotinamide (NI) mimic with PARP-1 inhibitory activity in the high micromolar range (IC50 = 5.75 μM) could be transformed into highly active derivatives with only marginal increase in molecular weight. Convenient one to two synthetic steps allowed us to explore extensive SAR at the 2-, and 5- through 8-positions of the quinazolin-4(3H)-one scaffold. Substitutions at the 2- and 8-positions were found to be most favorable for improved PARP-1 inhibition. The amino group at 8-position resulted in compound 22 with an IC50 value of 0.76 μM. Combination of the 8-amino substituent with an additional methyl substituent at the 2-position provided the most potent compound 31 [8-amino-2-methylquinazolin- 4(3H)-one, IC50 = 0.4 μM] in the present study. Compound 31 inhibited the proliferation of Brca1-deficient cells with an IC50 value of 49.0 μM and displayed >10-fold selectivity over wild type counterparts. Binding models of these derivatives within the active site of PARP-1 have further supported the SAR data and will be useful for future lead optimization efforts.
- Kulkarni, Shridhar S.,Singh, Satyakam,Shah, Janki R.,Low, Woon-Kai,Talele, Tanaji T.
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experimental part
p. 264 - 273
(2012/07/14)
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- 3-HYDROQUINAZOLIN-4-ONE DERIVATIVES FOR USE AS STEAROYL COA DESATURASE INHIBITORS
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The present invention discloses 3-hydroquinazolm-4-one derivatives for use as inhibitors of stearoyl-CoA desaturase. The compounds are useful in treating and/or preventing various human diseases, mediated by stearoyl-CoA desaturase (SCD) enzymes, especial
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Page/Page column 81-82
(2010/06/15)
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- ATP competitive kinase inhibitors
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The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.
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Page/Page column 10
(2008/06/13)
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