- Biomimetic alloxan-catalyzed intramolecular redox reaction with O2: One-pot atom-economic synthesis of sulfinyl-functionalized benzimidazoles
-
Given the necessity of sacrificial reductants in various biomimetic aerobic oxygenations, alloxan-catalyzed aerobic redox system for one-pot atom-economic synthesis of sulfinyl-functionalized benzimidazoles was developed by ingeniously binding both the substrate sulfide and sacrificial reductant. This mild and transition-metal-free protocol undergoes two oxidations without additional sacrificial reagents, except for the environmentally benign molecular oxygen.
- Zhang, Shiqi,Yi, Dong,Li, Guangxun,Li, Ling,Zhao, Gang,Tang, Zhuo
-
-
- A green and practical reduction of N-(4-chlorophenyl)-2-nitroaniline and its derivatives to corresponding N-substituted-benzene-1,2-diamines using thiourea dioxide
-
A new effective approach for synthesizing diverse N-substituted-benzene-1,2-diamines is reported. The treatment of N-substituted-2-nitroanilines with thiourea dioxide in the presence of sodium hydroxide efficiently formed the corresponding N-substituted-benzene-1,2-diamines, including N-(4-chlorophenyl)benzene-1,2-diamine with a good yield of 94%. The by-product is environmentally-friendly urea and is easy to separate from the product by filtration procedure that enhances the convenience of the approach.
- Cui, Jian-Lan,Wang, Ning,Wang, Xiao,Yu, Si-Yuan,Zhong, Cong-Shan
-
-
- Design, synthesis and biological evaluation of novel 4-phenoxypyridine based 3-oxo-3,4-dihydroquinoxaline-2-carboxamide derivatives as potential c-Met kinase inhibitors
-
Blocking c-Met kinase activity by small-molecule inhibitors has been identified as a promising approach for the treatment of cancers. Herein, we described the design, synthesis, and biological evaluation of a series of 4-phenoxypyridine-based 3-oxo-3,4-dihydroquinoxaline derivatives as c-Met kinase inhibitors. Inhibitory activitives against c-Met kinase evaluation indicated that most of compounds showed excellent c-Met kinase activity in vitro, and IC50 values of ten compounds (23a, 23e, 23f, 23l, 23r, 23s, 23v, 23w, 23x and 23y) were less than 10.00 nM. Notably, three of them (23v, 23w and 23y) showed remarkable potency with IC50 values of 2.31 nM, 1.91 nM and 2.44 nM, respectively, and thus they were more potent than positive control drug foretinib (c-Met, IC50 = 2.53 nM). Cytotoxic evaluation indicated the most promising compound 23w showed remarkable cytotoxicity against A549, H460 and HT-29 cell lines with IC50 values of 1.57 μM, 0.94 μM and 0.65 μM, respectively. Furthermore, the acridine orange/ethidium bromide (AO/EB) staining, cell apoptosis assays by flow cytometry, wound-healing assays and transwell migration assays on HT-29 and/or A549 cells of 23w were performed. Especially compound 23w, which displayed potent antitumor, apoptosis induction and antimetastatic activity, could be used as a promising lead for further development. Meanwhile, their preliminary structure-activity relationships (SARs) were also discussed.
- Wang, Zhen,Shi, Jiantao,Zhu, Xianglong,Zhao, Wenwen,Gong, Yilin,Hao, Xuechen,Hou, Yunlei,Liu, Yajing,Ding, Shi,Liu, Ju,Chen, Ye
-
-
- One-pot propagation of (Hetero)Arylamines: Modular synthesis of diverse Amino-di(hetero)arylamines
-
Formal propagation of (hetero)arylamine is achieved via a one-pot Buchwald–Hartwig C–N cross-coupling and nitro reduction sequence, enabling a rapid modular synthesis of diverse amino-di(hetero)arylamines from (hetero)arylamines and halogenated nitrobenzenes. Various functionalized aromatic amines with different electronic and steric environments can be efficiently prolongated to formally incorporate another arylamino fragments. This approach has been successfully applied in the synthesis of more than forty amino-di(hetero)arylamines. The applicability of this method has also been demonstrated in the synthesis of oligoanilines and the tyrosine-kinase inhibitor Imatinib.
- Liang, Xueting,Xu, Liang,Li, Cuihua,Jia, Xin,Wei, Yu
-
p. 721 - 731
(2019/01/08)
-
- Synthesis, anticancer activity and molecular docking studies on 1,2-diarylbenzimidazole analogues as anti-tubulin agents
-
Twenty-four 1,2-diarylbenzimidazole derivatives were designed, synthesized and biologically evaluated. It turned out that most of them were potential anticancer drugs. Among them, compound c24 showed the highest anti-tumor activity (GI50 = 0.71–2.41 μM against HeLa, HepG2, A549 and MCF-7 cells), and low toxicity to normal cells (CC50 > 100 μM against L02 cells). In the microtubule binding assay, c24 showed the most potent inhibition of microtubule polymerization (IC50 = 8.47 μM). The binding ability of compound c24 to tubulin crystal was verified by molecular docking simulation experiment. Further studies on HepG2 and HeLa cells showed that compound c24 could cause mitotic arrest of tumor cells to G2/M phase then inducing apoptosis. To sum up, compound c24 is a promising microtubule assembly inhibitor.
- Zhang, Ya-Liang,Yang, Rong,Xia, Lin-Ying,Man, Ruo-Jun,Chu, Yi-Chun,Jiang, Ai-Qin,Wang, Zhong-Chang,Zhu, Hai-Liang
-
-
- INHIBITING CONNEXIN 46 TO TREAT GLIOBLASTOMA AND OTHER CONDITIONS
-
Provided herein are compositions, systems, kits, and methods for treating a disease or condition by administering to a subject an agent that inhibits connexin 46 (Cx46) (e.g., ondancetron, an ondancetron analog or derivative, testosterone, a testosterone
- -
-
Page/Page column 28; 29
(2019/04/16)
-
- A robust multifunctional ligand-controlled palladium-catalyzed carbonylation reaction in water
-
A novel, hydrophilic and recyclable methoxypolyethylene glycol (PEG)-modulated s-triazine-based multifunctional Schiff base/N,P-ligand L9 was prepared and used in Pd-catalyzed Heck-type carbonylative coupling reactions, affording diverse chalcone derivatives and 1,4-dicarbonyl esters in good yields.
- Gao, Pei-Sen,Zhang, Kan,Yang, Ming-Ming,Xu, Shan,Sun, Hua-Ming,Zhang, Jin-Lei,Gao, Zi-Wei,Zhang, Wei-Qiang,Xu, Li-Wen
-
supporting information
p. 5074 - 5077
(2018/05/26)
-
- Design, synthesis and antifungal activity of novel fenfuram-diarylamine hybrids
-
Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC50value of 0.037 mg/L, far superior to the commercially available fungicide boscalid (EC50= 1.71 mg/L) and lead fungicide fenfuram (EC50= 6.18 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.
- Wang, Hongyu,Gao, Xuheng,Zhang, Xiaoxiao,Jin, Hong,Tao, Ke,Hou, Taiping
-
-
- SMALL MOLECULE INHIBITORS OF DYRK1A AND USES THEREOF
-
This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a benzimidazole or imidazopyridine structure which function as inhibitors of DYRK1A protein, and their use as therapeutics for the treatment of Alzheimer's disease, Down syndrome, glioblastoma, autoimmune diseases, inflammatory disorders (e.g., airway inflammation), and other diseases.
- -
-
-
- Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors
-
A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety were synthesized and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against five cancer cell lines (HT-29, H460, A549, MKN-45 and U87MG) in vitro. Most of the compounds exhibited moderate-to-significant cytotoxicity as compared with foretinib. The most promising compound 41 (with c-Met IC50 value of 0.90?nM) showed remarkable cytotoxicity against HT-29, H460, A549, MKN-45 and U87MG cell lines with IC50 values of 0.06?μM, 0.05?μM, 0.18?μM, 0.023?μM and 0.66?μM, respectively, and thus it was 1.22- to 3.50-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.
- Liu, Ju,Yang, Di,Yang, Xiuxiu,Nie, Minhua,Wu, Guodong,Wang, Zhunchao,Li, Wei,Liu, Yajing,Gong, Ping
-
p. 4475 - 4486
(2017/07/22)
-
- Synthesis and biological evaluation of novel pyrazole carboxamide with diarylamine-modi?ed scaffold as potent antifungal agents
-
Twenty-seven novel pyrazole carboxamides with diarylamine-modi?ed scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. Among them, compound 9c-7 exhibited the highest antifungal activities against R. solani, R. cerealis and S. sclerotiorum in vitro with IC50 values of 0.013, 1.608 and 1.874?μg/mL, respectively. Notably, compound 9c-7 still presented the highest fungicidal activities against R. solani in vivo with an IC50 value of 22.21?μg/mL. Molecular docking simulation results reveal that compound 9c-7 binds well to the hydrophobic pockets of the receptor protein succinate dehydrogenase. This study suggests that compound 9c-7 could act as a potential fungicide to be used for further optimization.
- Zhang, Xiao-Xiao,Jin, Hong,Deng, Yuan-Jie,Gao, Xu-Heng,Li, Yong,Zhao, Yong-Tian,Tao, Ke,Hou, Tai-Ping
-
p. 1731 - 1736
(2017/07/27)
-
- Imidazolyl amide compounds and uses related thereto
-
This disclosure relates to antiviral compounds disclosed herein and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising 2-((benzo[d]imidazol-2-yl)thio)-N-phenylpropanamide derivatives, N-phenyl-2-
- -
-
-
- Host-directed inhibitors of myxoviruses: Synthesis and in vitro biochemical evaluation
-
Drugs targeted to viral proteins are highly vulnerable to the development of viral resistance. One little explored approach to the treatment of viral diseases is the development of agents that target host factors required for virus replication. Myxoviruses are predominantly associated with acute disease and, thus, ideally suited for this approach since the necessary treatment time is anticipated to be limited. High-throughput screening previously identified benzimidazole 22407448 with broad antiviral activity against different influenza virus and paramyxovirus strains. Hit to lead chemistry has generated 6p (JMN3-003) with potent antiviral activity against a panel of myxovirus family members exhibiting EC50 values in the low nanomolar range.
- Sun, Aiming,Ndungu, J. Maina,Krumm, Stefanie A.,Yoon, Jeong-Joong,Thepchatri, Pahk,Natchus, Michael,Plemper, Richard K.,Snyder, James P.
-
p. 798 - 803
(2011/12/16)
-
- Benzimidazole and imidazole inhibitors of histone deacetylases: Synthesis and biological activity
-
A series of N-hydroxy-3-[3-(1-substituted-1H-benzoimidazol-2-yl)-phenyl]-acrylamides (5a-5ab) and N-hydroxy-3-[3-(1,4,5-trisubstituted-1H-imidazol-2-yl)-phenyl]-acrylamides (12a-s) were designed, synthesized, and found to be nanomolar inhibitors of human histone deacetylases. Multiple compounds bearing an N1-piperidine demonstrate EC50s of 20-100 nM in human A549, HL60, and PC3 cells, in vitro and in vivo hyperacetylation of histones H3 and H4, and induction of p21waf. Compound 5x displays efficacy in human tumor xenograft models.
- Bressi, Jerome C.,Jong, Ron de,Wu, Yiqin,Jennings, Andy J.,Brown, Jason W.,O'Connell, Shawn,Tari, Leslie W.,Skene, Robert J.,Vu, Phong,Navre, Marc,Cao, Xiaodong,Gangloff, Anthony R.
-
scheme or table
p. 3138 - 3141
(2010/09/03)
-
- Discovery of novel, orally available benzimidazoles as melanin concentrating hormone receptor 1 (MCHR1) antagonists
-
Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays role in several disorders such as obesity, stress, depression and anxiety. The synthesis and biological evaluation of novel benzimidazole derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified.
- Sasmal, Pradip K.,Sasmal, Sanjita,Rao, P. Tirumala,Venkatesham,Roshaiah,Abbineni, Chandrasekhar,Khanna, Ish,Jadhav, Vikram P.,Suresh,Talwar, Rashmi,Muzeeb, Syed,Receveur, Jean-Marie,Frimurer, Thomas M.,Rist, ?ystein,Elster, Lisbeth,H?gberg, Thomas
-
scheme or table
p. 5443 - 5448
(2011/01/03)
-
- PIPERIDINE DERIVATIVES AS HUMAN PAPILLOMA VIRUS INHIBITORS
-
HPV inhibitors with formula (I) where G1 represents a hydrocarbonated bond or chain possibly substituted by one or two alkyl groups, G2 represents a group (see formula Ia+Ib) or R represents a hydrogen, an alkyl, halogenoalkyl, or a prodrug radical such as carbamate, acetyl or dialkylaminomethyl, G represents a bond or a hydrocarbonated chain possibly substituted by one or two alkyls, W represents an oxygen or sulphur, R1 and R2 each represent a group chosen from among hydrogen, halogen, hydroxyl, thio, alkoxy, halogenoalkoxy, alkylthio, halogenoalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or halogenoalkyl, R3 represents an acid or a prodrug radical of the acid function or a bioisostere of the acid function, A represents an aryl, cycloalkyl, cycloalkenyl or a heterocycle, each possibly substituted, and B represents an aryl or a heterocycle with 6 chains, each possibly substituted, and pharmaceutically acceptable salts.
- -
-
Page/Page column 15
(2009/09/05)
-
- 4-(Benzimidazol-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: Potent and selective p70S6 kinase inhibitors
-
We report herein the design and synthesis of 4-(benzimidazol-2-yl)-1,2,5-oxadiazol-3-amine derivatives as inhibitors of p70S6 kinase. Screening hits containing the 4-(benzimidazol-2-yl)-1,2,5-oxadiazol-3-ylamine scaffold were optimized for p70S6K potency and selectivity against related kinases. Structure-based design employing an active site homology model derived from PKA led to the preparation of benzimidazole 5-substituted compounds 26 and 27 as highly potent inhibitors (Ki 100-fold selectivity against PKA, ROCK and GSK3.
- Bandarage, Upul,Hare, Brian,Parsons, Jonathan,Pham, Ly,Marhefka, Craig,Bemis, Guy,Tang, Qing,Moody, Cameron Stuver,Rodems, Steve,Shah, Sundeep,Adams, Chris,Bravo, Jose,Charonnet, Emmanuelle,Savic, Vladimir,Come, Jon H.,Green, Jeremy
-
scheme or table
p. 5191 - 5194
(2010/03/24)
-
- ARYL SULFAMIDE DERIVATIVES AND METHODS OF THEIR USE
-
The present invention is directed to aryl sulfamide derivatives of formula (I): or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof, which are monoamine reuptake inhibitors, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions, including, inter alia, vasomotor symptoms, sexual dysfunction, gastrointestinal disorders and genitourinary disorder, depression disorders, endogenous behavioral disorders, cognitive disorders, diabetic neuropathy, pain, and other diseases or disorders.
- -
-
Page/Page column 90
(2008/12/06)
-
- Polymer-assisted parallel solution phase synthesis of substituted benzimidazoles
-
A small library of benzimidazoles was prepared using polymer-bound reagents and scavengers. Polymer-assisted reaction of diphenyl diamines with carboxylic acids yielded o-amido-diphenylamines in the presence of Polystyrene-Carbodiimide (PS-Carbodiimide) u
- Yun, Young K.,Porco Jr., John A.,Labadie, Jeff
-
p. 739 - 742
(2007/10/03)
-