A new approach to the facile synthesis of 2-substituted-quinazolin-4（3H）-ones and its derivatives using the condensation reaction of substituted 2-aminobenzamide and orthoesters is reported.
A novel difluorocarbene promoted single-atom skeletal editing of 2H-indazoles is demonstrated herein.Ethyl bromodifluoroacetate was severed as the difluorocarbene source in the current protocol,facilitating the cleava...A novel difluorocarbene promoted single-atom skeletal editing of 2H-indazoles is demonstrated herein.Ethyl bromodifluoroacetate was severed as the difluorocarbene source in the current protocol,facilitating the cleavage of the N-N bond via carbon atom insertion.This metal-free ring expansion reaction enables the late-stage diversification of indazole skeletons,assembling a diverse array of functionalized quinazolin-4(3H)-ones in decent yields with excellent functional group compatibility.展开更多
采用密度泛函理论中的广义梯度近似（DFT/GGA）方法,在PW91/DNP水平上研究了21种2,3-二取代喹唑啉-4（3H）-酮化合物的结构、化学活性和前线轨道.结果表明：此类化合物的能隙Eg大部分都在3.50-3.60 e V之间,其中在喹唑啉环3位上取代甲...采用密度泛函理论中的广义梯度近似（DFT/GGA）方法,在PW91/DNP水平上研究了21种2,3-二取代喹唑啉-4（3H）-酮化合物的结构、化学活性和前线轨道.结果表明：此类化合物的能隙Eg大部分都在3.50-3.60 e V之间,其中在喹唑啉环3位上取代甲氧基苄基,或是在8位上取代甲基,化合物的能隙降低,而且甲氧基在苄基的间位比对位降低得更厉害.通过比较还发现,2,3-二取代喹唑啉-4（3H）-酮化合物对水稻纹枯菌（Rhizoctonia solani bacteria）的杀菌活性与哌啶并噻吩并嘧啶酮衍生物对水稻纹枯菌的杀菌活性相当,而哌啶并噻吩并嘧啶酮衍生物比2,3-二取代喹唑啉-4（3H）-酮化合物对苹果轮纹病（Botryospuaeria gregaria bacteria）杀菌活性好.展开更多
This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly(ADP-ribose)polymerase-1(PARP1)and bromodomain containing protein 4(BRD4),which had important cross relation in the global...This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly(ADP-ribose)polymerase-1(PARP1)and bromodomain containing protein 4(BRD4),which had important cross relation in the global network of breast cancer,reflecting the synthetic lethal effect.A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragmentbased combinatorial screening and activity assays that together led to the chemical optimization.Among these compounds,19 d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1,respectively.Compound 19 d was further shown to efficiently modulate the expression of BRD4 and PARP1.Subsequently,compound 19 d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase.Following pharmacokinetic studies,compound 19 d showed its antitumor activity in breast cancer susceptibility gene 1/2(BRCA1/2)wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight.These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.展开更多
A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized u...A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized using an L-proline catalyzed one-pot multi-component reaction approach.All the synthesized compounds were characterized and screened for their antimicrobial,antifungal and anti-tubercular activities.展开更多
The title compound 3,3＇-（2,2＇-（ethane-1,2-diylbis（oxy））bis（ethane-2,1-diyl））bis（2- （4-chlorophenylamino）quinazolin-4（3H）-one） 3 （C34H30CI2N604, Mr = 657.54） has been synthesized and its crystal struc...The title compound 3,3＇-（2,2＇-（ethane-1,2-diylbis（oxy））bis（ethane-2,1-diyl））bis（2- （4-chlorophenylamino）quinazolin-4（3H）-one） 3 （C34H30CI2N604, Mr = 657.54） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in space group P1 with a = 9.9185（8）, b = 10.6124（9）, c = 15.4064（13） A, α = 92.896（2）,β = 103.813（2）, γ= 94.635（2）°, V= 1565.5（2） A3, Z = 2, Dc = 1.395 g/cm^3,μ = 0.257 mm^-1, F（000） = 684, the final R = 0.0580 and wR = 0.1284 for 3400 observed reflections （I〉 2σ（I）. It remains triclinic in the crystal. Intra- and intermolecular N（3）-H（3A）…O（2）, N（6）-H（6A）…O（3） and C（19）-H（19A）…O（4） #1 （#1： 1-x, 1-y, -z） hydrogen bonds are observed in the title compound. A two-dimensional chain network is formed from the dimmers and intermolecular π-π interactions in the crystal structure. This open network has solvent-accessible voids （10A3）.展开更多
A heteropolyacid efficiently catalyzed the cyclocondensation reaction of 2‐aminobenzamide and salicylamide with aldehydes and ketones to afford good yields of benzoxazine and quinazoline ring systems in an aqueous me...A heteropolyacid efficiently catalyzed the cyclocondensation reaction of 2‐aminobenzamide and salicylamide with aldehydes and ketones to afford good yields of benzoxazine and quinazoline ring systems in an aqueous medium. The method gives clean reactions, has simple workup procedure, and uses environment friendly conditions.展开更多
基金the Natural Science Foundation of China(Nos.U0832005,90813011,20772159,30801436)the Ministry of Education of the People's Republic of China(No.200805581163)+1 种基金the Guangdong Natural Science Foundation(No.8451008901000214)the Science Foundation of Guangzhou(No.2009A1-E011-6)for financial support of this study.
文摘A new approach to the facile synthesis of 2-substituted-quinazolin-4（3H）-ones and its derivatives using the condensation reaction of substituted 2-aminobenzamide and orthoesters is reported.
基金supported by the National Natural Science Foundation of China(21931013,22271105)the Natural Science Foundation of Fujian Province(2022J02009)+1 种基金the Science and Technology Research Project of Education Department of Hubei Province(B2021133)the Hubei Key Laboratory of Pollutant Analysis&Reuse Technology(PA190109)
文摘A novel difluorocarbene promoted single-atom skeletal editing of 2H-indazoles is demonstrated herein.Ethyl bromodifluoroacetate was severed as the difluorocarbene source in the current protocol,facilitating the cleavage of the N-N bond via carbon atom insertion.This metal-free ring expansion reaction enables the late-stage diversification of indazole skeletons,assembling a diverse array of functionalized quinazolin-4(3H)-ones in decent yields with excellent functional group compatibility.
基金financial support from the National Natural Science Foundation of China(grant Nos.81922064,81874290 and 81673455 to Liang Ouyang,grant No.81673455 to Bo Liu,grant Nos.81573290 and U1603123 to Jie Liu)project of Science and Technology Department of Sichuan Province(grant No.20YYJC3921 to Jie Liu,China)
文摘This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly(ADP-ribose)polymerase-1(PARP1)and bromodomain containing protein 4(BRD4),which had important cross relation in the global network of breast cancer,reflecting the synthetic lethal effect.A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragmentbased combinatorial screening and activity assays that together led to the chemical optimization.Among these compounds,19 d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1,respectively.Compound 19 d was further shown to efficiently modulate the expression of BRD4 and PARP1.Subsequently,compound 19 d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase.Following pharmacokinetic studies,compound 19 d showed its antitumor activity in breast cancer susceptibility gene 1/2(BRCA1/2)wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight.These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.
文摘A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized using an L-proline catalyzed one-pot multi-component reaction approach.All the synthesized compounds were characterized and screened for their antimicrobial,antifungal and anti-tubercular activities.
基金supported by the Open Fund of Ministry-of-education Key Laboratory for the Synthesis and Application of Organic Functional Molecules (No. 2006-KL-013)
文摘The title compound 3,3＇-（2,2＇-（ethane-1,2-diylbis（oxy））bis（ethane-2,1-diyl））bis（2- （4-chlorophenylamino）quinazolin-4（3H）-one） 3 （C34H30CI2N604, Mr = 657.54） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in space group P1 with a = 9.9185（8）, b = 10.6124（9）, c = 15.4064（13） A, α = 92.896（2）,β = 103.813（2）, γ= 94.635（2）°, V= 1565.5（2） A3, Z = 2, Dc = 1.395 g/cm^3,μ = 0.257 mm^-1, F（000） = 684, the final R = 0.0580 and wR = 0.1284 for 3400 observed reflections （I〉 2σ（I）. It remains triclinic in the crystal. Intra- and intermolecular N（3）-H（3A）…O（2）, N（6）-H（6A）…O（3） and C（19）-H（19A）…O（4） #1 （#1： 1-x, 1-y, -z） hydrogen bonds are observed in the title compound. A two-dimensional chain network is formed from the dimmers and intermolecular π-π interactions in the crystal structure. This open network has solvent-accessible voids （10A3）.
基金the Research Council of Mazandaran University for the partial support of this work
文摘A heteropolyacid efficiently catalyzed the cyclocondensation reaction of 2‐aminobenzamide and salicylamide with aldehydes and ketones to afford good yields of benzoxazine and quinazoline ring systems in an aqueous medium. The method gives clean reactions, has simple workup procedure, and uses environment friendly conditions.
