31601-41-9Relevant academic research and scientific papers
SYNTHETIC ANALOGS OF Peganum ALKALOIDS. I. SYNTHESIS OF METHOXY- AND HYDROXY-SUBSTITUTED DEOXYVASICINONES AND DEOXYPEGANINES
Karimov, A.,Telezhenetskaya, M. V.,Yunusov, S. Yu.
, p. 466 - 472 (1982)
6-Methoxy-, 7-methoxy-, and 8-methoxydeoxyvasicinones have been synthesized by the reaction of substituted (3-methoxy-, 4-methoxy-, and 5-methoxy-) anthranilic acids with α-pyrrolidone.The demethylation of these compounds has given the corresponding hydroxy-substituted analogs of deoxyvasicinone, and the reduction of the products obtained with zinc in hydrochloric acid has given the hydroxy- and methoxy- analogs of deoxypeganine. 8-Hydrooxydeoxypeganine dimethyl-, ethyl-, and butylcarbamates have been obtained by the carbamoylation of 8-hydroxydeoxypeganine.
An organocatalytic C-C bond cleavage approach: A metal-free and peroxide-free facile method for the synthesis of amide derivatives
Vodnala, Nagaraju,Gujjarappa, Raghuram,Polina, Saibabu,Satheesh, Vanaparthi,Kaldhi, Dhananjaya,Kabi, Arup K.,Malakar, Chandi C.
supporting information, p. 20940 - 20944 (2020/12/31)
A facile organocatalytic approach has been devised towards the synthesis of amide derivatives using 1,3-dicarbonyls as easily available acyl-sources under peroxide-free reaction conditions. This transformation was accomplished by the cleavage of the C-C bond in the presence of TEMPO as an organocatalyst and excludes the use of transition-metals and harsh reaction conditions. A broad range of substrates with diverse functional groups were well tolerated and delivered the products in high yields.
Discovery and optimization of novel N-benzyl-3,6-dimethylbenzo[d]isoxazol-5-amine derivatives as potent and selective TRIM24 bromodomain inhibitors with potential anti-cancer activities
Hu, Qingqing,Wang, Chao,Xiang, Qiuping,Wang, Rui,Zhang, Cheng,Zhang, Maofeng,Xue, Xiaoqian,Luo, Guolong,Liu, Xiaomin,Wu, Xishan,Zhang, Yan,Wu, Donghai,Xu, Yong
, (2019/12/26)
Tripartite motif-containing protein 24 (TRIM24), recognized as an epigenetic reader for acetylated H3K23 (H3K23ac) via its bromodomain, has been closely involved in tumorigenesis or tumor progression of several cancers. Developing inhibitors of TRIM24 is significant for functional studies and drug discovery. Herein, we report the identification, optimization and evaluation of N-benzyl-3,6-dimethylbenzo[d]isoxazol-5-amines as TRIM24 bromodomain inhibitors starting from an in house library screening. Structure-based optimization leads to two potent and selective compounds 11d and 11h in an Alphascreen assay with IC50 values of 1.88 μM and 2.53 μM, respectively. The viability assay demonstrates the great potential of this series of compounds as inhibitors of proliferation of prostate cancer (PC) cells LNCaP, C4-2B. A colony formation assay further supports this inhibitory activity. Compounds 11d and 11h inhibit cell proliferation of other cancer types such as non-small cell lung cancer (NSCLC) cells A549 with IC50 values of 1.08 μM and 0.75 μM, respectively. These data suggests that compounds 11d and 11h are promising lead compounds for further research.
Copper-Catalyzed Site-Selective Oxidative C?C Bond Cleavage of Simple Ketones for the Synthesis of Anilides and Paracetamol
Vodnala, Nagaraju,Gujjarappa, Raghuram,Hazra, Chinmoy K.,Kaldhi, Dhananjaya,Kabi, Arup. K.,Beifuss, Uwe,Malakar, Chandi C.
supporting information, p. 135 - 145 (2018/12/05)
A copper-catalyzed approach for the N-acylation of anilines with acetone and acetophenones via C?C bond cleavage is described. Under the developed conditions both CHCl3 and CH2Cl2 were identified as potential C1-source to promote the transformation. The reaction features a site selective C?C bond cleavage to install the amide moieties with high functional-group compatibility and wide substrate scope. The developed method avoids the use of sensitive and narcotic agents. The method also represents an excellent complement to the previous protocols with lower E-factor (13.91 mg/1 mg) than current industrially used method (E-factor 17.54 mg/1 mg). The developed approach has also been extended for the effective preparation of pyridine derivatives and paracetamol in gram scale. The course of the reaction was monitored by 1H NMR as a preliminary investigation of the reaction mechanism. (Figure presented.).
Structure-Based Discovery and Optimization of Benzo [d] isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC)
Zhang, Maofeng,Zhang, Yan,Song, Ming,Xue, Xiaoqian,Wang, Junjian,Wang, Chao,Zhang, Cheng,Li, Chenchang,Xiang, Qiuping,Zou, Lingjiao,Wu, Xishan,Wu, Chun,Dong, Baijun,Xue, Wei,Zhou, Yulai,Chen, Hongwu,Wu, Donghai,Ding, Ke,Xu, Yong
, p. 3037 - 3058 (2018/04/23)
The bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.
A kind of benzo [d] different wicked zuozuo apperception compound and use thereof
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Paragraph 0163-0166, (2018/06/14)
The invention relates to the technical field of chemical medicine, and particularly discloses a benzo[d]isoxazole compound shown as a general formula (A) and application thereof. The compound can effectively inhibit bromodomain of BET family proteins so as to block interaction between the BET family proteins and chromatin histone to adjust genetic transcription, cause changing of a downstream signal path and exert important influence on various diseases, so that the compound and a combination thereof can be used for preparing medicine for treating or preventing diseases like tumorigenesis, inflammation, viral infection, cell proliferation disorder, autoimmune diseases and septicemia.
Direct synthesis of N-arylamides via the coupling of aryl diazonium tetrafluoroborates and nitriles under transition-metal-free conditions
Xiong, Biquan,Wang, Gang,Xiong, Tao,Wan, Liming,Zhou, Congshan,Liu, Yu,Zhang, Panliang,Yang, Changan,Tang, Kewen
supporting information, p. 3139 - 3142 (2018/07/13)
The direct synthesis of N-arylamides via the coupling of aryl diazonium tetrafluoroborates and nitriles under transition-metal-free conditions has been developed. The reported protocol is practical and represents an efficient method to produce functionalized amides in moderate to good yields.
Sulfonium Salts as Alkylating Agents for Palladium-Catalyzed Direct Ortho Alkylation of Anilides and Aromatic Ureas
Simkó, Dániel Cs.,Elekes, Péter,Pázmándi, Vivien,Novák, Zoltán
, p. 676 - 679 (2018/02/09)
A novel method for the ortho alkylation of acetanilide and aromatic urea derivatives via C-H activation was developed. Alkyl dibenzothiophenium salts are considered to be new reagents for the palladium-catalyzed C-H activation reaction, which enables the transfer of methyl and other alkyl groups from the sulfonium salt to the aniline derivatives under mild catalytic conditions.
Substituted quinolinone inhibitor
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Paragraph 0269-0272, (2018/09/08)
The invention provides a substituted quinolinone inhibitor and relates to a compound as shown in a formula (II) which is described in the specification or a pharmaceutically acceptable salt, solvate,active metabolite, polymorphic substance, ester, isomer or prodrug thereof, a pharmaceutical composition containing the compound as shown in the formula (II), and application of the compound and the pharmaceutical composition to treatment of diseases related to abnormal TOPK activity.
Phenyl [...] compound and its preparation method, pharmaceutical composition, drug use (by machine translation)
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Paragraph 0569; 0571; 0572; 0573, (2016/10/27)
The invention provides a phenylurea coupling quinazoline compound or a pharmaceutically acceptable salt thereof represented by formula (I), wherein R1 represents H, represents Br, Cl or F, represents -CH3, -CH2-CH3, -CH2(CH3)2 or -CF3, represents -O-CH3, -O-CH2-CH3 or -O-CH2(CH3)2, or represents -C[triple bond]CH or -C[triple bond]N; n1 is 1, 2, 3, 4 or 5; one of R2 and R3 is a group represented by formula (II); R4 represents H, represents Br, Cl or F, represents -CH3, -CH2-CH3, -CH2(CH3)2 or -CF3, represents -O-CH3, -O-CH2-CH3 or -O-CH2(CH3)2, represents -NH2, or represents -NO2; n2 is 1, 2, 3, 4 or 5; and the other one of R2 and R3 represents H, -O-CH3, -O-CH2-CH3, -O-CH2(CH3)2, or the following groups.
