- Tandem Synthesis of 2-Carboxybenzofurans via Sequential Cu-Catalyzed C-O Coupling and Mo(CO)6-Mediated Carbonylation Reactions
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A modular tandem synthesis of 2-carboxybenzofurans from 2-gem-dibromovinylphenols has been established based on a sequence of Cu-catalyzed intramolecular C-O coupling and Mo(CO)6-mediated intermolecular carbonylation reactions. This protocol allowed one-step access to a broad variety of functionalized benzofuran-2-carboxylic acids, esters, and amides in good to excellent yields under Pd- and CO gas-free conditions.
- Mo, Qinliang,Sun, Nan,Jin, Liqun,Hu, Baoxiang,Shen, Zhenlu,Hu, Xinquan
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p. 11490 - 11500
(2020/10/12)
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- Synthesis and biological evaluation of novel shikonin-benzo[b]furan derivatives as tubulin polymerization inhibitors targeting the colchicine binding site
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A novel series of shikonin-benzo[b]furan derivatives were designed and synthesized as tubulin polymerization inhibitors, and their biological activities were evaluated. Most compounds revealed the comparable anti-proliferation activities against the cancer cell lines to that of shikonin and simultaneously low cytotoxicity to non-cancer cells. Among them, compound 6c displayed powerful anti-cancer activity with the IC50 value of 0.18 μM against HT29 cells, which was significantly better than that of the reference drugs shikonin and CA-4. What's more, 6c could inhibit tubulin polymerization and compete with [3H] colchicine in binding to tubulin. Further biological studies depicted that 6c can induce cell apoptosis and cell mitochondria depolarize, regulate the expression of apoptosis related proteins in HT29 cells. Besides, 6c actuated the HT29 cell cycle arrest at G2/M phase, and influenced the expression of the cell-cycle related protein. Moreover, 6c displayed potent inhibition on cell migration and tube formation that contributes to the antiangiogenesis. These results prompt us to consider 6c as a potential tubulin polymerization inhibitor and is worthy for further study.
- Kong, Ling-Yi,Leng, Jia-Fu,Lian, Bao-Ping,Shao, Yu-Ying,Xia, Yuan-Zheng,Yin, Yong
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- Halogenated benzofuran-coumarin derivative and application thereof to preparation of anti-fouling agent
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The invention relates to a halogenated benzofuran-coumarin derivative and application thereof to preparation of an anti-fouling agent. The preparation method of the halogenated benzofuran-coumarin derivative comprises the following steps: carrying out a backflow reaction on 6-amino coumarin and 5-chlorobenzenefuran-2-formaldehyde in an organic solvent for 5-6 hours, naturally cooling to the room temperature, and adding sodium borohydride in an ice bath to react for 4-5 hours, thereby obtaining the halogenated benzofuran-coumarin derivative of a structure of formula I as shown in the specification.
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Paragraph 0023-0025
(2019/09/17)
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- TBAI/TBHP mediated oxidative cross coupling of ketones with phenols and carboxylic acids: Direct access to benzofurans
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TBAI/TBHP mediated oxidative cross coupling of phenols and carboxylic acids with ketones has been reported under metal-free, base free, solvent free conditions enabling environmentally benign synthesis of aryloxyketones, acyloxy ketones and benzofurans. Phenoxyketones and acyloxylcarbonyl compounds were synthesized in good to high yields, where as benzofurans were synthesized in moderate yields. This method is operationally simple, works under mild conditions, using commercially available as well as inexpensive TBAI and an oxidant TBHP.
- Santhosh Kumar,Ravikumar,Chinna Ashalu,Rajender Reddy
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supporting information
p. 33 - 37
(2017/12/11)
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- Synthesis and biological evaluation of novel Ani9 derivatives as potent and selective ANO1 inhibitors
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Anoctamin 1 (ANO1), a calcium-activated chloride channel, is highly expressed and amplified in a number of carcinomas including breast, pancreatic and prostate cancers. Downregulation of ANO1 expression and function significantly inhibits cell proliferation, migration, and invasion of various cancer cell lines. Development of potent and selective ANO1 inhibitors is currently desirable, which may provide a new strategy for cancer treatment. Our previous study revealed a new class of ANO1 inhibitor, (E)-2-(4-chloro-2-methylphenoxy)-N'-(2-methoxybenzylidene)acetohydrazide (Ani9) and structural optimization via chemical modification of Ani9 basic skeleton was undertaken for the development of more potent and specific inhibitors of ANO1. Structure-activity relationship studies with newly synthesized derivatives revealed a number of potent ANO1 inhibitors, among which 5f is the most potent inhibitor with an IC50 value of 22 nM. The selectivity analyses showed that 5f has excellent selectivity to ANO1 (>1000-fold over ANO2). In cellular assays, 5f significantly inhibited cell proliferation of PC3, MCF7, and BxPC3 cells expressing high levels of ANO1. In addition, 5f strongly reduced the protein levels of ANO1 in PC3 cells. This study will be useful in the development of ANO1 inhibitors for treatment of cancer and other ANO1-related diseases.
- Seo, Yohan,Kim, Jinhwang,Chang, Jiwon,Kim, Seong Soon,Namkung, Wan,Kim, Ikyon
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p. 245 - 255
(2018/10/24)
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- Efficient synthesis of chiral benzofuryl β-amino alcohols via a catalytic asymmetric Henry reaction
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Chiral β-amino alcohol ligands were found effective for the copper(ii)-catalyzed asymmetric Henry reaction of benzofuran-2-carbaldehydes with nitromethane, which led to the formation of (S)-enriched benzofuryl β-nitro alcohols with satisfactory enantioselectivities (up to 98% ee). Using this catalytic protocol, bioactive (S)-benzofuryl β-amino alcohols could be conveniently prepared in short steps.
- Chen, Wei,Zhou, Zhao-Hui,Chen, Hong-Bin
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p. 1530 - 1536
(2017/02/15)
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- INHIBITORS OF DRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS
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The present invention provides novel indoleamide compounds for treating tuberculosis, including drug-resistant M-tuberculosis, compositions comprising the indoleamides and methods of using the indoleamides in conjunction with other biologically active agents for the treatment of tuberculosis in a subject in need thereof.
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Page/Page column 21
(2015/11/16)
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- Preliminary structure - Activity relationships and biological evaluation of novel antitubercular indolecarboxamide derivatives against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains
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Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world's population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent antitubercular agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure-activity relationships (SARs). These efforts led to the identification of three molecules (12-14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis, with minimum inhibitory concentration (MIC) values lower than those of the most prominent antitubercular agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay.
- Onajole, Oluseye K.,Pieroni, Marco,Tipparaju, Suresh K.,Lun, Shichun,Stec, Jozef,Chen, Gang,Gunosewoyo, Hendra,Guo, Haidan,Ammerman, Nicole C.,Bishai, William R.,Kozikowski, Alan P.
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supporting information
p. 4093 - 4103
(2013/06/27)
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- Convenient synthesis of some 3-phenyl-1-benzofuran-2-carboxylic acid derivatives as new potential inhibitors of ClC-Kb channels
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Improved experimental conditions were carried out for the preparation in high yields of some 3-phenyl-1-benzofuran-2-carboxylic acids, potent inhibitors of ClC-K chloride channels. A one-pot condensation-cyclization was set up starting from different 2-hy
- Piemontese, Luca,Carbonara, Giuseppe,Fracchiolla, Giuseppe,Laghezza, Antonio,Tortorella, Paolo,Loiodice, Fulvio
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experimental part
p. 2865 - 2872
(2011/04/24)
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- Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part I: Exploration of 5-6 fused rings as alternative S1 moieties
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A series of cis-1,2-diaminocyclohexane derivatives were synthesized with the aim of optimizing previously disclosed factor Xa (fXa) inhibitors. The exploration of 5-6 fused rings as alternative S1 moieties resulted in two compounds which demonstrated improved solubility and reduced food effect compared to the clinical candidate, compound A. Herein, we describe the synthesis and structure-activity relationship (SAR), together with the physicochemical properties and pharmacokinetic (PK) profiles of some prospective compounds.
- Yoshikawa, Kenji,Yokomizo, Aki,Naito, Hiroyuki,Haginoya, Noriyasu,Kobayashi, Shozo,Yoshino, Toshiharu,Nagata, Tsutomu,Mochizuki, Akiyoshi,Osanai, Ken,Watanabe, Kengo,Kanno, Hideyuki,Ohta, Toshiharu
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experimental part
p. 8206 - 8220
(2010/04/06)
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- Aminostyrylbenzofuran derivatives as potent inhibitors for Aβ fibril formation
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The synthesis of a novel series of aminostyrylbenzofuran derivatives 1a-w and their inhibitory activities for Aβ fibril formation were described. All the synthesized compounds were evaluated by thioflavin T (ThT) assay and displayed potent inhibitory activities for Aβ fibril formation. Among them, compounds 1i and 1q exhibited excellent inhibitory activities (IC50 = 0.07 and 0.08 μM, respectively) than those of Curcumin (IC50 = 0.80 μM) and IMSB (IC50 = 8.00 μM) as reference compounds. Both compounds were selected as promising candidates for further biological evaluation.
- Byun, Ji Hun,Kim, HyeYun,Kim, YoungSoo,Mook-Jung, Inhee,Kim, Dong Jin,Lee, Won Koo,Yoo, Kyung Ho
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scheme or table
p. 5591 - 5593
(2009/06/18)
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- New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central α2-antagonistic activity as potential antidepressants
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The synthesis and biological activity of a series of benzofuro[3,2- c]pyridines and a benzothieno[3,2-c]pyridine are described. These compounds exhibit high affinity for the α2-adrenoceptor, with high selectivity versus the α1-receptor. Compound 1 also shows potent in vivo central activity and has been selected for further biological and clinical evaluation.
- Kennis, Ludo E.J.,Bischoff, Francois P.,Mertens, Carolus J.,Love, Christopher J.,Van den Keybus, Frans A.F.,Pieters, Serge,Braeken, Mirielle,Megens, Anton A.H.P.,Leysen, Josee E.
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- Inhibition of aromatase (P450Arom) by some 1-(benzofuran-2-ylmethyl)imidazoles.
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Studies of a series of 1-(benzofuran-2-ylmethyl)imidazoles, 1-5, previously proposed as potential agents for prostatic cancer by their inhibition of 17beta-hydroxylase:17,20-lyase (P450 17), have been extended to their selectivity against placental microsomal aromatase (P450(Arom)) in man. The compounds were 3-7-fold more potent than aminoglutethimide and had some selectivity for P450 17 as expressed by the ratio (IC50 P450(Arom))/(IC50 P450) 17)/17.0 (2), 10.3 (3), 34.6 (4) and 42.0 (5), where IC50 is the concentration resulting in 50% inhibition. The lower potency of 1-5 towards P450(Arom) compared with the racemic alpha-phenyl-substituted compounds (6, 80-1000 x aminoglutethimide) and some racemic alpha-methyl (8.5 and 12.2 x aminoglutethimide) and alpha-ethyl (12.1 and 32.9 x aminoglutethimide) analogues has been rationalized. This work selectively extends studies of the P450 17 inhibitor 5, a potential prostatic cancer agent, towards other cytochrome P450 enzymes in the steroidogenic pathway and provides a general method for determining the relative influence of chemical manipulation of a parent inhibitor towards two enzymes in the pathway using additional literature data.
- Owen,Nicholls,Smith,Whomsley
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p. 427 - 433
(2007/10/03)
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- α-Adrenoreceptor Reagents. 2. Effects of Modification of the 1,4-Benzodioxan Ring System on α-Adrenoreceptor Activity
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Modification of the 1,4-benzodioxan ring present in RX 781094 (1) has not previously been considered.This paper describes a number of analogues of this ring system, including compounds in which one of the oxygen atoms has been replaced by a methylene group and also those in which the ring size has been changed to give, for example, furan and thiophene derivatives.The dihydroxybenzofuranylimidazoline compound 7 is the only analogue possesing presynaptic antagonist potency and selectivity comparable to that of 1.In view of this result, a number of derivatives was prepared to determine the structure-activity relationships within this series.Many derivatives, as well as the parent compound 7, were found to possess presynaptic α2-adrenoreceptor antagonist and postsynaptic α1-adrenoreceptor partial agonist properties.Two of the selective presynaptic antagonists,13 and 14, possess greater potency and selectivity than that possessed by 1.The 5-chloro derivative 25 is twice as potent as 1 after oral administration but only about half as potent when given intravenously.
- Chapleo, Christopher B.,Myers, Peter L.,Butler, Richard C. M.,Davis, John A.,Doxey, John C.,et al.
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p. 570 - 576
(2007/10/02)
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