104795-85-9Relevant articles and documents
Axially chiral 3,3′-bi(1-benzothiophene)-2,2′-dicarboxylic acid and its derivatives
Mezlova, Marie,Petrickova, Hana,Malon, Petr,Kozmik, Vaclav,Svoboda, Jiri
, p. 1020 - 1038 (2003)
Ullmann dimerization of substituted methyl 3-X-1-benzothiophene-2-carboxylates 1-7 (X = Cl, Br) gave rise to the corresponding dimeric 3,3′-bi(1-benzothiophene) esters 8-13. Resolution of the title acid 20 by fractional crystallization of its mono- and bisquininium salt afforded pure (R)- and (S)-enantiomers, the optical purity and absolute configuration of which was confirmed by CD spectrometry and by X-ray crystallography. Ullmann dimerization of chiral oxazolines 23 and 24 derived from 2 proceeded without any diastereodifferentiation. Reduction of (R)- and (S)-20 afforded the corresponding (R)- and (S)-diols 29, which served as chiral ligands in a model enantioselective reduction of acetophenone. (R)- and (S)-1-phenylethan-1-ol were formed in 28 and 29% e.e., respectively.
Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors
Li, Wen-Zhen,Xi, Hui-Zhi,Wang, Yi-Jie,Ma, Hong-Bo,Cheng, Zhi-Qiang,Yang, Yu,Wu, Meng-Ling,Liu, Ting-Mei,Yang, Wen,Wang, Qin,Liao, Meng-Ya,Xia, Yong,Zhang, Yi-Wen
, p. 835 - 849 (2021)
As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.
Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents
Zhao, Liyu,Sun, Yin,Yin, Wenbo,Tian, Linfeng,Sun, Nannan,Zheng, Yang,Zhang, Chu,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
, (2021/11/22)
To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03–0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25–2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study.
Discovery of fluorescent coumarin-benzo[b]thiophene 1, 1-dioxide conjugates as mitochondria-targeting antitumor STAT3 inhibitors
Cai, Guiping,Yu, Wenying,Song, Dongmei,Zhang, Wenda,Guo, Jianpeng,Zhu, Jiawen,Ren, Yuhao,Kong, Lingyi
, p. 236 - 251 (2019/05/02)
STAT3 has been extensively studied as a potential antitumor target. Though studies on regulating STAT3 mainly focus on the inhibition of STAT3 phosphorylation at Tyr705 residue, the phosphorylation at Ser727 residue of STAT3 protein is also closely associated with the mitochondrial import of STAT3 protein. N, N-diethyl-7-aminocoumarin is a fluorescent mitochondria-targeting probe. In this study, a series of STAT3 inhibitors were developed by connecting N, N-diethyl-7-aminocoumarin fluorophore with benzo [b]thiophene 1, 1-dioxide moiety. All designed compounds displayed potent anti-proliferative activity against cancer cells. The representative compound 7a was mainly accumulated in mitochondria visualized by its fluorescence. STAT3 phosphorylation was inhibited by compound 7a at both Tyr705 and Ser727 residues. Compound 7a inhibited STAT3 phosphorylation whereas had no influence on the phosphorylation levels of STAT1, JAK2, Src and Erk1/2, indicating good selectivity of compound 7a. Moreover, compound 7a down-regulated the expression of STAT3 target genes Bcl-2 and Cyclin D1, increased ROS production and remarkably reduced the mitochondrial membrane potential to induce mitochondrial apoptotic pathway. Furthermore, compound 7a in vivo suppressed breast cancer 4T1 implanted tumor growth. Taken together, these results highlighted that compound 7a might be a promising mitochondria-targeting STAT3 inhibitor for cancer therapy.
GEMINAL SUBSTITUTED QUINUCLIDINE AMIDE COMPOUNDS AS AGONISTS OF ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTORS
-
Paragraph 00268, (2016/07/05)
The present invention relates to novel geminal substituted quinuclidine amide compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7- nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.
Palladium-catalyzed domino C-S coupling/carbonylation reactions: An efficient synthesis of 2-carbonylbenzo[ b ]thiophene derivatives
Zeng, Fanlong,Alper, Howard
supporting information; experimental part, p. 2868 - 2871 (2011/07/07)
A facile and selective palladium-catalyzed domino procedure has been developed for the preparation of 2-carbonylbenzo[b]thiophene derivatives from 2-gem-dihalovinylthiophenols. This protocol involves intramolecular C-S coupling/intermolecular carbonylatio
Discovery of a new series of potent and selective linear tachykinin NK 2 receptor antagonists
Fedi, Valentina,Altamura, Maria,Catalioto, Rose-Marie,Giannotti, Danilo,Giolitti, Alessandro,Giuliani, Sandro,Guidi, Antonio,Harmat, Nicholas J. S.,Lecci, Alessandro,Meini, Stefania,Nannicini, Rossano,Pasqui, Franco,Tramontana, Manuela,Triolo, Antonio,Maggi, Carlo Alberto
, p. 4793 - 4807 (2008/03/12)
Starting from 1 (MEN 14268), a selective tachykinin NK2 receptor antagonist with an interesting in vitro pharmacological profile, a family of numerous antagonists was obtained through an optimization process focused on iterated structural modifications. The effects of the introduction of a wide variety of substituents on the lipophilic aromatic part of the molecule and the modulation of the structural constraint through the insertion of different achiral α,α-dialkylamino acids were investigated. In particular, aromatic and benzofused heteroaromatic moieties were introduced at the pseudo-N-terminal residue to replace the 2-benzothiophene moiety, and a systematic investigation of the best positioning of substituents onto the aromatic platform was reported for the benzothiophene core. Studies on the modulation of the length and the rigidity of the hydrophilic pseudo-C-terminal pendant are presented. Many heteroaliphatic groups are well tolerated by the receptor in this part of the ligand. The product 48f (MEN15596), bearing a methyl substituent on the benzothiophene and a tetrahydropyranylmethylpiperidine pendant, was finally selected for its good in vivo activity after intravenous, intraduodenal, and oral administration in guinea pigs.
Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors
Capkova, Katerina,Yoneda, Yoshiyuki,Dickerson, Tobin J.,Janda, Kim D.
, p. 6463 - 6466 (2008/04/02)
Botulinum neurotoxins are the most toxic proteins currently known. Based on a recently identified potent lead structure, 2,4-dichlorocinnamic acid hydroxamate, herein we report on the structure-activity relationship of a series of hydroxamate BoNT/A inhibitors. Among them, 2-bromo-4-chlorocinnamic acid hydroxamate, 2-methyl-4-chlorocinnamic acid hydroxamate, and 2-trifluoromethyl-4-chlorocinnamic acid hydroxamate displayed comparable inhibitory activity to that of the lead structure.
Heteroaryl and benzyl amide compounds
-
Page/Page column 13, (2008/06/13)
Compounds of formula I processes for their preparation, their use as pharmaceuticals and to pharmaceutical compositions comprising them.
