75754-04-0Relevant articles and documents
Biosynthesis of Mycotoxin Fusaric Acid and Application of a PLP-Dependent Enzyme for Chemoenzymatic Synthesis of Substituted l -Pipecolic Acids
Hai, Yang,Chen, Mengbin,Huang, Arthur,Tang, Yi
supporting information, p. 19668 - 19677 (2020/12/01)
Fusaric acid (FA) is a well-known mycotoxin that plays an important role in plant pathology. The biosynthetic gene cluster for FA has been identified, but the biosynthetic pathway remains unclarified. Here, we elucidated the biosynthesis of FA, which features a two-enzyme catalytic cascade, a pyridoxal 5′-phosphate (PLP)-dependent enzyme (Fub7), and a flavin mononucleotide (FMN)-dependent oxidase (Fub9) in synthesizing the picolinic acid scaffold. FA biosynthesis also involves an off-line collaboration between a highly reducing polyketide synthase (HRPKS, Fub1) and a nonribosomal peptide synthetase (NRPS)-like carboxylic acid reductase (Fub8) in making an aliphatic α,β-unsaturated aldehyde. By harnessing the stereoselective C-C bond-forming activity of Fub7, we established a chemoenzymatic route for stereoconvergent synthesis of a series of 5-alkyl-, 5,5-dialkyl-, and 5,5,6-trialkyl-l-pipecolic acids of high diastereomeric ratio.
Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis
Liu, Mingming,Liang, Yuru,Zhu, Zhongzhen,Wang, Jin,Cheng, Xingxing,Cheng, Jiayi,Xu, Binpeng,Li, Rong,Liu, Xinhua,Wang, Yang
, p. 9299 - 9314 (2019/10/16)
In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 μM) with no obvious cytotoxicity (CC50 > 50 μM). It effectively attenuated hypoxia-induced HIF-1α protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.
Transition-Metal-Free Decarboxylative Arylation of 2-Picolinic Acids with Arenes under Air Conditions
Zhang, Xitao,Feng, Xiujuan,Zhou, Chuancheng,Yu, Xiaoqiang,Yamamoto, Yoshinori,Bao, Ming
supporting information, p. 7095 - 7099 (2018/11/23)
A facile, transition-metal-free, and direct decarboxylative arylation of 2-picolinic acids with simple arenes is described. The oxidative decarboxylative arylation of 2-picolinic acids with arenes proceeds readily via N-chloro carbene intermediates to afford 2-arylpyridines in satisfactory to good yields under transition-metal-free conditions. This new type of decarboxylative arylation is operationally simple and scalable and exhibits high functional-group tolerance. Various synthetically useful functional groups, such as halogen atoms, methoxycarbonyl, and nitro, remain intact during the decarboxylative arylation of 2-picolinic acids.
Design, synthesis and biological evaluation of phenylpicolinamide sorafenib derivatives as antitumor agents
Wu, Chunjiang,Xu, Shan,Guo, Yuping,Wu, Jielian,Luo, Rong,Wang, Wenhui,Tu, Yuanbiao,Le Chen,Zhu, Wufu,Zheng, Pengwu
, p. 374 - 387 (2017/10/07)
Two series of phenylpicolinamide sorafenib derivatives (14a–k, 15a–k) were designed and synthesized. They were evaluated for IC50 values against three cancer cell lines (A549, Hela, and MCF-7) and VEGFR2/KDR, BRAF, and CRAF kinases. Fourteen target compounds showed moderate to excellent cytotoxicity activity against the different cancer cells with potency from the single-digit μM to nanomole range. What’s more, six of them were equal to more potent than sorafenib against one or more cell lines. Most of the compounds showed bad activity against VEGFR2/KDR, BRAF, or CRAF kinases. The most promising compound 15f showed strong antitumor activities against A549 and MCF-7 cell lines with IC50 values of 5.43 ± 0.74 and 0.62 ± 0.21 μM, which were 1.29–6.79-fold more active than sorafenib (6.53 ± 0.82, 4.21 ± 0.62 μM), respectively and it exhibited moderate IC50 (7.1 μM) than 14f (IC50 = 3.1 μM). Structure–activity relationships (SARs) and docking studies indicated that replacement of diarylurea of sorafenib with phenylpicolinamide moiety benefits to the activity. The position of aryl group and the substitutions of aryl group have a great influence on antitumor activity and selectivity. Small volume groups of aryl group such as (substituted) alkyl groups (–CH3, –CF3), halogen atoms (–F) were favorable to the cytotoxicity. Exact action mechanism of target compounds is not quite clear and further study will be carried out to identify the target in near future.
Fusaric acid and analogues as Gram-negative bacterial quorum sensing inhibitors
Tung, Truong Thanh,Jakobsen, Tim Holm,Dao, Trong Tuan,Fuglsang, Anja Thoe,Givskov, Michael,Christensen, S?ren Br?gger,Nielsen, John
supporting information, p. 1011 - 1020 (2016/12/30)
Taking advantage of microwave-assisted synthesis, efficient and expedite procedures for preparation of a library of fusaric acid and 39 analogues are reported. The fusaric acid analogues were tested in cell-based screening assays for inhibition of the las and rhl quorum sensing system in Pseudomonas aeruginosa and the lux quorum sensing system in Vibrio fischeri. Eight of the 40 compounds in the library including fusaric acid inhibited lux quorum sensing and one compound inhibited activity of the las quorum sensing system. To our delight, none of the compounds showed growth inhibitory effects in the tested concentration ranges.
Synthesis, biological evaluation and docking studies of sorafenib derivatives N-(3-fluoro-4-(pyridin-4-yloxy)phenyl)-4(5)-phenylpicolinamides
Wang, Min,Wu, Chunjiang,Xu, Shan,Zhu, Yan,Li, Wei,Zheng, Pengwu,Zhu, Wufu
, p. 176 - 185 (2017/03/08)
Background: Sorafenib is an important VEGFR2/KDR inhibitor which is widely used for the treatment of cancer. Objective: In this paper, two series of sorafenib analogues N-(3-fluoro-4-(pyridin-4-yloxy)phenyl)-4- phenylpicolinamides(13a-k) and N-(3-fluoro-4-(pyridin-4-yloxy)phenyl)-5-phenylpicolinamides (14a-k) were designed and synthesized. Methods: Their structures were confirmed by various analytical methods, such as 1 H and 13 C NMR, m.p., MS, HRMS. All of them were evaluated for IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). Results: Eleven of the synthesized compounds showed moderate to excellent cytotoxicity activity against different cancer cells, whose potency from single-digit μM to nanomolar range. And five of them were equal to more potent than sorafenib against one or more cell lines. The most promising compound 14c showed excellent antitumor activities against PC-3 and MCF-7 cell lines with IC50 values of 2.62±1.07 μM and 1.14±0.92 μM, which were 1.15 to 2.75-fold more active than sorafenib (3.03±1.01 μM, 3.14±1.65 μM), respectively. Conclusion: Structure-activity relationships (SARs) and docking studies indicated that the replacement of diarylurea of sorafenib with phenylpicolinamide moiety benefited to the activity. The position of aryl group and the substituents of aryl group had a great influence on antitumor activity and selectivity. The aryl groups with the substitute of alkyl groups (-CH3), halogen atoms (-F,Cl) were favorable to the cytotoxicity. However, this series of compounds showed moderate activity against VEGFR2/KDR kinase. Mechanism of target compounds was not quite clear and further study will be carried out to identify the possible target.
An efficient synthetic approach towards new 5,5’-diaryl-2,2’-bipyridine-based fluorophores
Krinochkin, Alexey P.,Kopchuk, Dmitry S.,Chepchugov, Nikolay V.,Kim, Grigory A.,Kovalev, Igor S.,Rahman, Matiur,Zyryanov, Grigory V.,Majee, Adinath,Rusinov, Vladimir L.,Chupakhin, Oleg N.
supporting information, p. 1099 - 1103 (2017/05/19)
An efficient approach has been developed for the synthesis of 5,5′-diaryl-2,2′-bipyridines via their 1,2,4-triazine analogues. The notable advantages of the present method are: The possibility of varying the aromatic substituents in the positions 5 and 5′ of bipyridine core and the possibility for obtaining 2,2′-bipyridines bearing a fused cyclopentene core to increase the solubility in organic solvents. These 5,5′-diaryl-2,2′-bipyridines exhibited an intense emission in a range of ca. 422–521?nm in acetonitrile solution; depending on the nature of the aromatic substituents and the presence of annulated cyclopentene fragments. Apart from that, the significant bathochromic shifts of the both absorption and emission maxima were observed in comparison with a number of previously described similar structures. In some cases the significant increasing of the fluorescence quantum yields took place.
Novel indole derivative and medicine containing the same (by machine translation)
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Paragraph 0103; 0107, (2018/06/30)
[A] formation of Amyloid fibrils can be compounds, including therapeutic or prophylactic agent for neurodegenerative disease Amyloid fibrils formation inhibitor compound and of. (I) or its pharmaceutically acceptable compound represented by the formula [a] or a salt or solvate thereof includes the, Amyloid fibrils formation inhibitor. [R1 And R2 Each independently is H, an alkyl group, a cyano group or the like; R3 And R4 Each independently is H, or an alkyl group; R3 And R4 The, joint may form a ring; Ar1 And Ar2 The substituted or unsubstituted heteroaryl group are independently substituted/unsubstituted aryl groups /; X and Y are each independently a single bond, - (=O) - C etc., Z is O or CH2 ; N is an integer of 1 - 3][Drawing] no (by machine translation)
Design, synthesis, and docking studies of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors
Zhu, Wufu,Wang, Wenhui,Xu, Shan,Tang, Qidong,Luo, Rong,Wang, Min,Gong, Ping,Zheng, Pengwu
, p. 812 - 819 (2016/02/09)
Four series of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (12a-e, 13a-f, 14a-f and 15a-i) were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, PC-3 and MCF-7) and c-Met kinase. Five selected compounds (13b, 15b, 15d, 15e and 15f) were further evaluated for the activity against HepG2 and Hela cell lines. Eighteen of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 valuables in single-digit μM to nanomole range. Seven of them are equal to more active than positive control Foretinib against one or more cell lines. The most promising compound 15f showed superior activity to Foretinib, with the IC50 values of 1.04 ± 0.11 μM, 0.02 ± 0.01 μM and 9.11 ± 0.55 μM against A549, PC-3 and MCF-7 cell lines, which were 0.62 to 19.5 times more active than Foretinib (IC50 values: 0.64 ± 0.26 μM, 0.39 ± 0.11 μM, 9.47 ± 0.22 μM), respectively. Structure-activity relationships (SARs) and docking studies indicated that replacement of quinoline nucleus of the previous active compounds with 1H-pyrrolo[2,3-b]pyridine moiety maintained even improved the potent cytotoxic activity. The results suggested that the introduction of fluoro atoms to the aminophenoxy part of target compounds or the phenyl group of pyrimidine substituted on C-4 position was benefit for the activity.
Preparation of 5,6-diaryl-2,2-bipyridines using a 1,2,4-triazine methodology
Kopchuk,Chepchugov,Kim,Zyryanov,Kovalev,Rusinov,Chupakhin
, p. 897 - 900 (2015/12/24)
New unsymmetric 5,6-diaryl-2,2-bipyridines were synthesized in high yields using a 1,2,4-triazine methodology. Their photophysical properties were studied.
