- ARYL HYDROCARBON RECEPTOR LIGANDS AND THEIR ANALOGUES FOR THE PREVENTION AND TREATMENT OF INFLAMMATORY DISORDERS
-
Aryl hydrocarbon receptor (AHR) agonists and their use in treating or preventing or reducing the risk of an inflammatory disorder associated with a reduced expression of an aryl hydrocarbon receptor (AHR), including necrotizing enterocolitis, for preventing, reducing the risk of, or reducing the severity of an inflammatory disorder associated with a reduced expression of an aryl hydrocarbon receptor (AHR), and as an additive to infant nutritional formulas.
- -
-
Page/Page column 79-80
(2022/04/03)
-
- A new series of benzoxazole-based SIRT1 modulators for targeted therapy of non-small-cell lung cancer
-
In an attempt to identify potential anticancer agents for non-small-cell lung cancer (NSCLC) targeting sirtuin 1 (SIRT1), the synthesis of a new series of benzoxazoles (3a – i) was carried out through a facile and versatile synthetic route. The compounds were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cells using the MTT assay. 2-[(5-Nitro-1H-benzimidazol-2-yl)thio]-N-(2-methylbenzoxazol-5-yl)acetamide (3e) and 2-[(5-chloro-1H-benzimidazol-2-yl)thio]-N-(2-methylbenzoxazol-5-yl)acetamide (3g) were the most potent and selective anticancer agents in this series against the A549 cell line, with IC50 values of 46.66 ± 11.54 and 55.00 ± 5.00 μM, respectively. The flow cytometry-based apoptosis detection assay was performed to determine their effects on apoptosis in A549 cells. Both compounds induced apoptosis in a dose-dependent manner. The effects of compounds 3e and 3g on SIRT1 activity were determined. On the basis of in vitro studies, it was observed that compound 3g caused a significant decrease in SIRT1 levels in a dose-dependent manner, whereas compound 3e increased the SIRT1 levels. According to molecular docking studies, the substantial alteration in the type of action could be attributed to the difference between the interactions of compounds 3e and 3g with the same residues in the active site of SIRT1 (PDB code: 4IG9). On the basis of in silico ADME (absorption, distribution, metabolism, and excretion) studies, these compounds are predicted to possess favorable ADME profiles. According to the in vitro and in silico studies, compounds 3e and 3g, small-molecule SIRT1 modulators, were identified as potential orally bioavailable anticancer agents for the targeted therapy of NSCLC.
- Sever, Belgin,Akal?n ?ift?i, Gül?en,Alt?ntop, Mehlika Dilek
-
-
- Highly Diastereoselective Synthesis of Dihydro-benzoimidazo-[1,3]-thiazines via Electro-oxidative Selenocyclization of Thioallyl Benzoimidazoles
-
The current methodology reveals a green and proficient electro-oxidative tandem selenocyclization of thioallyl benzoimidazoles manufacturing selenylated dihydro-benzoimidazo-thiazine derivatives. Both C?Se and C?N bond formation were achieved via this mild protocol which exhibits good functional group tolerability affording an extensive range of substrate scope up to 96% isolated yields. Complete control over the regioselective formation of the six-membered heterocycle and stereoselective construction of the contiguous stereocenters was established. The practical electrochemical method operates in an undivided cell at ambient temperature without using any metal and external chemical oxidant.
- Halder, Atreyee,Mahanty, Kingshuk,Maiti, Debabrata,De Sarkar, Suman
-
supporting information
p. 3895 - 3899
(2021/10/23)
-
- Three-Component Synthesis of 2-Alkylthiobenzoazoles in Aqueous Media
-
A highly efficient three-component protocol for the synthesis of the 2-alkylthiobenzoazoles is described. Tetramethylthiuram disulfide (TMTD) cyclized with o -aminothiophenols, generating the intermediate 2-mercaptobenzothiazoles, and the successive C-S coupling with halogenated alkanes afforded a series of 2-alkyl-substituted thiobenzothiazoles smoothly in a one-pot process. This procedure could also be utilized for the preparation of 2-alkyl-substituted thiobenzoxazoles and 2-alkyl-substituted thiobenzimidazoles. Inexpensive and easily available starting materials, metal catalyst-free, broad substrate scope, and water as solvent are the features of this protocol.
- Chen, Jin-Quan,Dong, Zhi-Bing,Guo, Jia
-
p. 1927 - 1933
(2020/07/03)
-
- AlCl3-Promoted Synthesis of 2-Mercapto Benzoheterocycles by Using Sodium Dimethyldithiocarbamate as Thiocarbonyl Surrogate
-
A simple, expeditious and high-efficiency synthetic method for the AlCl3-mediated one-pot preparation of 2-mercapto benzoheterocycles (2-mercapto benzothiazoles, benzoxazoles and benzimidazoles) is described. By the treatment of a series of S, O and N heteroatoms containing bifunctional molecules with sodium dimethyldithiocarbamate in AlCl3, the desired benzoheterocycles are obtained smoothly. The protocol can also be applied on the synthesis of a series of thiazolidine-2-thiones, imidazolidine-2-thiones. This novel synthetic approach has advantages such as ligand-free, high efficiency, short reaction time, readily available starting materials and simple experimental procedures.
- Liu, Xing,Zhang, Shi-Bo,Dong, Zhi-Bing
-
p. 5406 - 5411
(2018/10/20)
-
- Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
-
PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
- Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
-
p. 6289 - 6304
(2017/08/02)
-
- An environmentally benign and efficient synthesis of substituted benzothiazole-2-thiols, benzoxazole-2-thiols, and benzimidazoline-2-thiones in water
-
An efficient and practical method for the one-step synthesis of benzothiazole-2-thiols, benzoxazole-2-thiols and benzimidazoline-2-thiones by cyclization of 2-aminothiophenols, 2-aminophenols, and 1,2-phenylenediamines with tetramethylthiuram disulfide (TMTD) in water was described. The features of this method include metal/ligand-free, excellent yield, short reaction time and broad substrate scope. The method provides a facile and convenient preparation of some potentially biologically active compounds.
- Liu, Xing,Liu, Min,Xu, Wan,Zeng, Meng-Tian,Zhu, Hui,Chang, Cai-Zhu,Dong, Zhi-Bing
-
p. 5591 - 5598
(2017/12/06)
-
- A Palladium Iodide-Catalyzed Cyclocarbonylation Approach to Thiadiazafluorenones
-
The first example of an additive cyclocarbonylation process leading to 1-thia-4a,9-diazafluoren-4-ones is reported. This process is based on the reaction of readily available 2-(propynylthio)benzimidazoles with carbon monoxide carried out in EtOH at 100 °C under a 5/2 mixture of CO-CO2 at 70 atm in the presence of the PdI2/KI catalytic system. Experimental evidence suggests a mechanistic pathway involving N-palladation of the substrate followed by CO insertion, triple bond insertion, protonolysis, and isomerization.
- Veltri, Lucia,Paladino, Veronica,Plastina, Pierluigi,Gabriele, Bartolo
-
p. 6106 - 6111
(2016/07/26)
-
- SAR156497, an exquisitely selective inhibitor of Aurora kinases
-
The Aurora family of serine/threonine kinases is essential for mitosis. Their crucial role in cell cycle regulation and aberrant expression in a broad range of malignancies have been demonstrated and have prompted intensive search for small molecule Auror
- Carry, Jean-Christophe,Clerc, Fran?ois,Minoux, Hervé,Schio, Laurent,Mauger, Jacques,Nair, Anil,Parmantier, Eric,Le Moigne, Ronan,Delorme, Cécile,Nicolas, Jean-Paul,Krick, Alain,Abécassis, Pierre-Yves,Crocq-Stuerga, Véronique,Pouzieux, Stéphanie,Delarbre, Laure,Maignan, Sébastien,Bertrand, Thomas,Bjergarde, Kirsten,Ma, Nina,Lachaud, Sylvette,Guizani, Houlfa,Lebel, Rémi,Doerflinger, Gilles,Monget, Sylvie,Perron, Sébastien,Gasse, Francis,Angouillant-Boniface, Odile,Filoche-Rommé, Bruno,Murer, Michel,Gontier, Sylvie,Prévost, Céline,Monteiro, Marie-Line,Combeau, Cécile
-
supporting information
p. 362 - 375
(2015/03/04)
-
- NOVEL VIRAL REPLICATION INHIBITOR
-
The present invention relates to a pharmaceutical composition for the treatment or prevention of viral infections comprising as an active principle at least one benzimidazole conjugates derivative havin the general formula I. The invention also relates to processes for the preparation of compounds according to the invention having above mentioned general formula and their use as a medicine or to treat or prevent viral infections.
- -
-
Page/Page column 15-16
(2008/06/13)
-
- Benzimidazole compound
-
An object of the present invention is to provide a novel chemical compound useful as a therapeutic or prophylactic agent for acid-related diseases, having an excellent inhibitory effect against gastric acid secretion, an excellent effect of maintaining the inhibitory effect against gastric acid secretion, thereby maintaining intragastric pH high for a long time, and having more safety and appropriate physicochemical stability. Provided is a compound represented by where R1 and R3 may be the same or different and each represent a hydrogen atom or a C1-C6 alkyl group; R2 represents (5,5-dimethyl-1,3-dioxan-2-yl)methoxy group, 5,7-dioxaspiro[2.5]oct-6-ylmethoxy group, 1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy group, or (2,2-dimethyl-1,3-dioxan-5-yl)methoxy group; R4, R5, R6 and R7 represent a hydrogen atom, halogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group or C1-C6 haloalkoxy group; and W1 represents a single bond, methylene or ethylene group, a salt thereof or a solvate of these.
- -
-
Page/Page column 76
(2008/06/13)
-
- 2,4-Bis (trifluoroethoxy)pyridine compound and drug containing the compound
-
The present invention is directed to a 2,4-bis(trifluoroethoxy)pyridine compound represented by formula (1): (wherein X1 represents a fluorine atom or a hydrogen atom) or a salt thereof, and to a drug containing the compound or the salt as an active ingredient. The compound has metabolic resistance in human liver microsome, good absorbability upon oral administration, and excellent ACAT inhibitory activity.
- -
-
-
- Structure-activity relationship of omeprazole and analogues as Helicobacter pylori urease inhibitors
-
Helicobacter pylori urease belongs to a family of highly conserved urea- hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K+-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K+- ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pK(a)-value of the pyridine, the pK(a)-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of β- mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 μmol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 μmol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.
- Kuhler,Fryklund,Bergman,Weilitz,Lee,Larsson
-
p. 4906 - 4916
(2007/10/03)
-
- HETEROCYCLIC SYSTEMS CONTAINING BRIDGEHEAD NITROGEN ATOMS. PART LXVIII. REACTION OF 5-FLUOROBENZIMIDAZOLYL-2-THIONE WITH CHLOROACETIC ACID: STUDIES OF ORIENTATION OF CYCLIZATION IN THE SYNTHESES OF 6-FLUORO- AND 7-FLUOROTHIAZOLOBENZIMIDAZOL-3(2H)-ONES
-
4-Fluoroaniline on successive acetylation, nitration and hydrolysis affords 4-fluoro-2-nitroaniline which on reduction with Raney nickel and hydrazine hydrate followed by treatment of the resulting diamine with carbon disulphide in situ gives 5-fluorobenzimidazolyl-2-thione.The thione on condensation with chloroacetic acid yields acetic acid which on cyclization in a mixture of acetic anhydride and pyridine furnishes two isomers viz. 6-fluoro- and 7-fluorothiazolobenzimidazol-3(2H)-ones.The condensation of thione with 1,2-dibromoethane affords sym-bis-(5-fluorobenzimidazo-2-yl-mercapto)ethane.The structural assignments for the 6-fluoro- and 7-fluorothiazolobenzimidazol-3(2H)-ones have been made by 1H-NMR spectral data using two different methods.
- Pujari, H. K.,Sharma, B. R.,Dahiya, Rajender,Kumar, Sudhir,Murakami, Yasuoki,Tani, Masanobu
-
p. 343 - 355
(2007/10/02)
-