- 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
-
supporting information
p. 766 - 772
(2021/12/22)
-
- Electrosynthesis of CF3-Substituted Polycyclic Quinazolinones via Cascade Trifluoromethylation/Cyclization of Unactivated Alkene
-
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
-
supporting information
p. 1319 - 1325
(2022/03/15)
-
- Design, synthesis, and evaluation of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides as antitumor agents
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In our continuing search for novel small-molecule anticancer agents, we designed and synthesized a series of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides (5), focusing on the modification of substitution in the quinazolin-4(3H)-one moiety. The biological evaluation showed that all 13 designed and synthesized compounds displayed significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5l displayed cytotoxicity up to 213-fold more potent than 5-fluorouracil and 87-fold more potent than PAC-1, the first procaspase-activating compound. Structure–activity relationship analysis revealed that substitution of either electron-withdrawing or electron-releasing groups at positions 6 or 7 on the quinazolin-4(3H)-4-one moiety increased the cytotoxicity of the compounds, but substitution at position 6 seemed to be more favorable. In the caspase activation assay, compound 5l was found to activate the caspase activity by 291% in comparison to PAC-1, which was used as a control. Further docking simulation also revealed that this compound may be a potent allosteric inhibitor of procaspase-3 through chelation of the inhibitory zinc ion. Physicochemical and ADMET calculations for 5l provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent.
- Dung, Do T. M.,Park, Eun J.,Anh, Duong T.,Hai, Pham-The,Huy, Le D.,Jun, Hye W.,Kwon, Joo-Hee,Young Ji,Kang, Jong S.,Tung, Truong T.,Dung, Phan T. P.,Han, Sang-Bae,Nam, Nguyen-Hai
-
-
- Visible-Light Photosynthesis of CHF2/CClF2/CBrF2-Substituted Ring-fused Quinazolinones in Dimethyl Carbonate
-
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
-
-
- Self-catalyzed phototandem perfluoroalkylation/cyclization of unactivated alkenes: Synthesis of perfluoroalkyl-substituted quinazolinones
-
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
-
supporting information
p. 1026 - 1031
(2021/02/06)
-
- Photoinduced homolytic decarboxylative acylation/cyclization of unactivated alkenes with α-keto acid under external oxidant and photocatalyst free conditions: access to quinazolinone derivatives
-
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
-
supporting information
p. 6050 - 6053
(2021/06/21)
-
- Photo-triggered self-catalyzed fluoroalkylation/cyclization of unactivated alkenes: Synthesis of quinazolinones containing the CF2R group
-
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
-
supporting information
p. 575 - 581
(2021/01/28)
-
- Visible-Light-Induced Radical Difluoromethylation/Cyclization of Unactivated Alkenes: Access to CF2H-Substituted Quinazolinones
-
A mild and efficient visible-light-induced radical difluoromethylation/cyclization of unactivated alkenes toward the synthesis of substituted quinazolinones with easily accessible difluoromethyltriphenylphosphonium bromide has been developed. The transformation has the advantages of wide functional group compatibility, a broad substrate scope, and operational simplicity. The benign protocol offers a facile access to pharmaceutically valuable difluoromethylated polycyclic quinazolinones.
- Chen, Xiaoyu,Liu, Bo,Pei, Congcong,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
-
supporting information
p. 7787 - 7791
(2021/10/20)
-
- Cobalt-Catalyzed Tandem Transformation of 2-Aminobenzonitriles to Quinazolinones Using Hydration and Dehydrogenative Coupling Strategy
-
A tandem synthesis of quinazolinones from 2-aminobenzonitriles is demonstrated here by using an aliphatic alcohol-water system. For this transformation, a cheap and easily available cobalt salt and P(CH2CH2PPh2)3 (PP3) ligand were employed. The substrate scope, scalability, and synthesis of natural products exhibited the vitality of this protocol.
- Samim, Sk. Abdus,Roy, Bivas Chandra,Nayak, Sourav,Kundu, Sabuj
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p. 11359 - 11367
(2020/10/12)
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- Imidazolium chloride as an additive for synthesis of 4(3H)-quinazolinones using anthranilamides and DMF derivatives
-
Imidazolium chloride as an environmentally benign additive efficiently facilitates construction of 4(3H)-quinazolinones using anthranilamides and DMF derivatives. A series of 4(3H)-quinazolinones were prepared in moderate to excellent yields without conventional oxidants, metal catalysts and corrosive acids or other additives.
- Dai, Zeshu,Li, Dan,Li, Zhiyao,Liu, Heng,Luo, Wen,Shang, Suqin,Tian, Qingqiang,Wang, Shuqi,Wang, Xuetong,Wang, Yin,Wu, Huili,Xiao, Xin,Yuan, Jianyong,Zhou, Shangjun
-
-
- Design, Synthesis and Bioevaluation of Two Series of 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-ones and N-(1-Benzylpiperidin-4-yl)quinazolin-4-amines
-
Two series of 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-ones and N-(1-benzylpiperidin-4-yl)quinazolin-4-amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N-(1-benzylpiperidin-4-yl)quinazolin-4-amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 percent in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N-(1-Benzylpiperidin-4-yl)quinazolin-4-amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC-3 (prostate cancer), and NCI?H23 (lung cancer), with 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one being the most cytotoxic agent. 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N-(1-benzylpiperidin-4-yl)quinazolin-4-amines could serve as new leads for further design and AChE inhibitors, while 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one could serve as a new lead for the design and development of more potent anticancer agents.
- Lan, Ta Thu,Anh, Duong Tien,Pham-The, Hai,Dung, Do Thi Mai,Park, Eun Jae,Jang, Sun Dong,Kwon, Joo Hee,Kang, Jong Soon,Thuan, Nguyen Thi,Han, Sang-Bae,Nam, Nguyen-Hai
-
-
- 3,4-DIHYDRO-4-OXOQUINAZOLINE-BASED ACETOHYDRAZIDES AND AN ANTICANCER COMPOSITION COMPRISING THE SAME AS AN ACTIVE INGREDIENT
-
The present invention relates to 3,4 - dihydro -4 -oxoquinazolinediazide and an anticancer composition comprising the same as an active ingredient. , It will be described below. 3,4 - Dihydro -4 - oxoquinazolin-based acetohydrazide according to the present invention activates procacaspase -3 to promote the conversion to caspase -3, and thus can be used as a proliferation inhibitor for various cancer cells. The compound according to the present invention can be developed as an active ingredient of a potent anticancer agent.
- -
-
Paragraph 0097-0098
(2020/12/11)
-
- A in the aqueous phase under microwave conditions using halogenated benzamide fast synthesis of quinazoline compounds of the method
-
The invention discloses a in the aqueous phase under microwave conditions using halogenated benzamide fast synthesis of quinazoline compounds of the method, the use of palladium chloride to serve as the catalyst, in water under microwave heating conditions, neighbouring halogen benzamide with an isocyanate reaction to produce the quinazoline compounds of the method, the invention an environment-friendly, the operation is simple, cheap and safe, efficient process for producing quinazoline compounds of the method. Compared with the prior art, this method not only can be applied to a large number of functional groups, the productive rate is high, few by-products, and the operation is simple, safe, low cost, environmental protection.
- -
-
Paragraph 0015; 0030
(2019/02/13)
-
- A in ammonia water condition of microwave halo benzoic acid synthesis method of the quinazoline compounds
-
The invention discloses a in ammonia water condition of microwave halo benzoic acid synthetic quinazoline compounds of the method, the use of palladium chloride to serve as the catalyst, in ammonia water under the microwave heating condition, neighbouring halogen benzoic acid generated by the reaction with the isocyanate of the quinazoline compounds of the method, the invention an environment-friendly, the operation is simple, cheap and safe, efficient process for producing quinazoline compounds of the method. Compared with the prior art, this method not only can be applied to a large number of functional groups, the productive rate is high, few by-products, and the operation is simple, safe, low cost, environmental protection.
- -
-
Paragraph 0017; 0032
(2019/02/13)
-
- IDENTIFICATION AND USE OF ERK5 INHIBITORS
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The present invention covers heterocyclic compounds of general formula (I) in which T, U, Y, Z, R1 and R3 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer disorders, as a sole agent or in combination with other active ingredients.
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Page/Page column 51; 67
(2019/10/01)
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- Novel N-Hydroxybenzamides or N-Hydroxypropenamides Incorporating Quinazolin-4(3H)-ones as Histone Deacetylase Inhibitors and Anticancer Composition Comprising the Same
-
The present invention relates to novel N-hydroxy benzamides or N-hydroxy propenamides based on quinazoline-4(3H)-ones as histone deacetylase (HDAC) inhibitors and a use thereof. More specifically, a compound according to the present invention has a strong HDAC inhibitory activity, thereby being able to be used as proliferation inhibitors for various cancer cells. Therefore, the compound according to the invention is expected to be able to be developed as an active component of strong anti-cancer drugs.COPYRIGHT KIPO 2019
- -
-
Paragraph 0135; 0136
(2019/05/15)
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- Novel Hydroxamic Acid Incorporating Quinazolin-4(3H)-ones as Histone Deacetylase Inhibitors and Anticancer Composition Comprising the Same
-
The compound according HDAC(histone deacetylase) to the present -4(3H)- won invention can, be used as an active. ingredient of, a potent anticancer agent, HDAC since the compound according, to the present invention can be used. as, an active ingredient of a potent anticancer agent, since the compound. according to the present invention can be used as an active ingredient of a potent anticancer agent. (by machine translation)
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Paragraph 0105-0106
(2020/03/03)
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- Quinazolin-4(3H)-one-Based Hydroxamic Acids: Design, Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity
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The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin-4(3H)-ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N-hydroxy-7-(7-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5b) and N-hydroxy-7-(6-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5c) (IC50 values, 0.10–0.16 μm) were found to be approximately 30-fold more cytotoxic than SAHA (IC50 values of 3.29–3.67 μm). N-Hydroxy-7-(4-oxoquinazolin-3(4H)-yl)heptanamide (5a; IC50 values of 0.21–0.38 μm) was approximately 10- to 15-fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC50 values in sub-micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c, strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.
- Hieu, Doan Thanh,Anh, Duong Tien,Hai, Pham-The,Thuan, Nguyen Thi,Huong, Le-Thi-Thu,Park, Eun Jae,Young Ji,Soon Kang, Jong,Phuong Dung, Phan Thi,Han, Sang-Bae,Nam, Nguyen-Hai
-
-
- Novel 3,4-dihydro-4-oxoquinazoline-based acetohydrazides: Design, synthesis and evaluation of antitumor cytotoxicity and caspase activation activity
-
In search for novel small molecules with antitumor cytotoxicity via activating procaspase-3, we have designed and synthesized three series of novel (E)-N′-benzylidene-4-oxoquinazolin-3(4H)-yl)acetohydrazides (5a-j, 6a-h, and 7a-h). On the phenyl ring ò the benzylidene part, three different substituents, including 2-OH-4-OCH3, 4-OCH3, and 4-N(CH3)2, were introduced, respectively. Biological evaluation showed that the acetohydrazides in series 5a-j, in which the phenyl ring of the benzylidene part was substituted by 2-OH-4-OCH3 substituent, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). Most of the compounds, in this series, especially compounds 5c, 5b and 5h, also significantly activated caspase-3 activity. Among these, compound 5c displayed 1.61-fold more potent than PAC-1 as caspase-3 activator. Cell cycle analysis showed that compounds 5b, 5c, and 5h significantly arrested the cell cycle in G1 phase. Further apoptotic studies also demonstrated compounds 5b, 5c, and 5h as strong apoptotic cell death inducers. The docking simulation studies showed that these compounds could activate procaspase via chelating Zn2+ ion bound to the allosteric site of the zymogen.
- Huan, Le Cong,Tran, Phuong-Thao,Phuong, Cao Viet,Duc, Phan Huy,Anh, Duong Tien,Hai, Pham The,Huong, Le Thi Thu,Thuan, Nguyen Thi,Lee, Hye Jin,Park, Eun Jae,Kang, Jong Soon,Linh, Nguyen Phuong,Hieu, Tran Trung,Oanh, Dao Thi Kim,Han, Sang-Bae,Nam, Nguyen-Hai
-
-
- Oxalic/malonic acids as carbon building blocks for benzazole, quinazoline and quinazolinone synthesis
-
An oxidant, base and metal free methodology has been developed for the synthesis of various 2-substituted and non-substituted benzazoles, quinazolines and quinazolinones using oxalic/malonic acids as an in situ carbon source. This methodology is applicable for a wide range of substituted o-phenylenediamine, o-aminothiophenol, o-aminophenol and o-aminobenzamide containing various functional groups and provides good to excellent yields of the corresponding product. Furthermore an easy workup procedure, high yield and easy isolation of products are key features of this methodology. The developed protocol is also applicable for the gram scale synthesis of benzimidazoles.
- Sharma, Saurabh,Bhattacherjee, Dhananjay,Das, Pralay
-
supporting information
p. 1337 - 1342
(2018/03/06)
-
- Quinazoline-Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity
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In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a?–?4i, 6a?–?6i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g?–?4i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC50 values in sub-micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.
- Hieu, Doan Thanh,Anh, Duong Tien,Hai, Pham-The,Huong, Le-Thi-Thu,Park, Eun Jae,Choi, Jeong Eun,Kang, Jong Soon,Dung, Phan Thi Phuong,Han, Sang-Bae,Nam, Nguyen-Hai
-
-
- Method of synthesizing quinazolinone derivative by using methanol as raw material
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The invention discloses a method of synthesizing a quinazolinone derivative by using methanol as a raw material. The method comprises adding an anthranilamide derivative II, methanol III and an iridium metal complex in a reaction container; performing a reaction on the reaction mixture in a microwave reactor or under magnetic stirring at a temperature of 130 +/- 10 DEG C for 2 hours or more; performing cooling to a room temperature; removing a solvent in a spin drying manner; and performing column separation to obtain a target compound. The method provided by the invention adopts nontoxic and renewable methanol as a raw material, and the by-products in the reaction are hydrogen gas and water, thus the method does not pollute the environment and meet the requirements of green chemistry, so that the method has a wide development prospect.
- -
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Paragraph 0040; 0041; 0042; 0043
(2017/12/06)
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- A microwave catalysis in the aqueous phase a method of preparing Quinazolinone compounds
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The invention discloses a method for preparing quinazolinone in water phase through microwave catalysis. The method comprises the step: by utilizing a water-soluble coordination compound (such as 8-hydroxyquinoline) as a catalyst, carrying out high-efficiency microwave catalysis on the reaction of 2-halogenated benzaldehyde and amidine salts in pure water phase. The invention relates to a method for preparing a quinazolinone compound, which is environment-friendly, simple and convenient to operate, safe and low-cost, and high-efficiency. Compared with the prior art, the method not only can be applicable to a great deal of functional groups, high in yield, fewer in side products, but also is simple and safe to operate, low in cost, and environment-friendly.
- -
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Paragraph 0056
(2017/02/09)
-
- Acceptorless Dehydrogenative Coupling of o-Aminobenzamides with the Activation of Methanol as a C1 Source for the Construction of Quinazolinones
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A strategy for the synthesis of quinazolinones via acceptorless coupling of o-aminobenzamides with methanol has been accomplished in the presence of the metal-ligand bifunctional catalyst [Cp?Ir(2,2′-bpyO)(H2O)]. Notably, this research exhibited the potential of transition-metal-catalyzed activation of methanol as a C1 source for the construction of heterocycles.
- Li, Feng,Lu, Lei,Liu, Pengcheng
-
supporting information
p. 2580 - 2583
(2016/06/15)
-
- 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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- Simple, selective, and practical synthesis of 2-substituted 4(3H)-quinazolinones by Yb(OTf)3-catalyzed condensation of 2-aminobenzamide with carboxamides
-
A simple, selective, and practical synthetic method of 4(3H)-quinazolinones is realized by Yb(OTf)3-catalyzed condensation of 2-aminobenzamide with carboxamides. As the reaction proceeds, NH3 and H2O were formed as byproducts; however, Yb(OTf)3 can operate as an efficient Lewis acid catalyst without deactivation.
- Yoshimura, Tsutomu,Yuanjun, Di,Kimura, Yu,Yamada, Hisatsugu,Toshimitsu, Akio,Kondo, Teruyuki
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p. 857 - 865
(2015/03/04)
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- THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
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-
Paragraph 0344; 0345; 0346
(2015/01/06)
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- THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases
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Page/Page column 50
(2013/07/19)
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- BICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS
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The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
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- Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP-ribose)polymerase-1 inhibitors
-
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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- RAF KINASE MODULATORS AND METHODS OF USE
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The present invention comprises a new class of compounds capable of modulating the activity of Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have a general Formula (I) wherein each of A1, A2, A3, A4, A5, A6, A7, A8, A9, bond B, X, rings Z1 and Z2, R1 and R3 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.
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Page/Page column 43; 58
(2009/01/24)
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- NITROGEN-CONTAINING BICYCLIC HETEROARYL COMPOUNDS AND METHODS OF USE
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The present invention comprises a new class of compounds capable of modulating Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have Formula (I) wherein R1 is Formula (II), (III) or (IV) and A1, A2, A3, A4, X, Z, Z', R1, R2, R3, R4, R5 and R6 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.
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Page/Page column 115-116
(2008/06/13)
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- Substituted oxoazaheterocyclyl compounds
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This invention is directed to oxoazaheterocycyl compounds which inhibit Factor Xa, to oxoazaheterocycyl compounds which inhibit both Factor Xa and Factor IIa, to pharmaceutical compositions comprising these compounds, to intermediates useful for preparing these compounds, to a method of directly inhibiting Factor Xa and to a method of simultaneously directly inhibiting Factor Xa and Factor IIa..
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Page/Page column 70
(2008/06/13)
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