- Biotransformation of phenylurea herbicides by a soil bacterial strain, Arthrobacter sp. N2: Structure, ecotoxicity and fate of diuron metabolite with soil fungi
-
In order to assess the influence of the aromatic substitution on the ability of a soil bacterial strain, Arthrobacter sp. N2, to degrade phenylurea herbicides, biotransformation assays were performed in mineral medium with resting cells of this soil bacterial strain on three phenylurea herbicides (diuron, chlorotoluron and isoproturon). Each herbicide considered, led to the formation of only one metabolite detected by HPLC analysis. After isolation, the metabolites were identified by NMR and MS, as the corresponding substituted anilines. According to the Microtox test (realized on the bacterium Vibrio fischeri), these metabolites presented non-target toxicity far more important (up to 600 times higher for 4-isopropylaniline) than the parent molecule. For isoproturon and chlorotoluron, the amount of substituted anilines obtained at the end of the biotransformation was very low, whereas the biotransformation of diuron into 3,4-dichloroaniline was almost quantitative. In this last case, the degradation product accumulated in the medium. In soil, other microorganisms are present that might degrade it. So the biotransformation of 3,4-dichloroaniline was then tested with four fungal strains: Aspergillus niger, Beauveria bassiana, Cunninghamella echinulata var. elegans and Mortierella isabellina. The aniline was further transformed with all the microorganisms tested. Only one metabolite was detected by HPLC analysis and after isolation, it was identified to be 3,4-dichloroacetanilide. This acetylated compound led to biological effects less important on V. fischeri than 3,4-dichloroaniline. These results stress the importance of identifying the degradation products to assess the impact of a polluting agent. Indeed, the pollutant may undergo transformation yielding compounds more toxic than the parent molecule.
- Tixier,Sancelme,Ait-Aissa,Widehem,Bonnemoy,Cuer,Truffaut,Veschambre
-
-
Read Online
- Design, synthesis, kinetic, molecular dynamics, and hypoglycemic effect characterization of new and potential selective benzimidazole derivatives as Protein Tyrosine Phosphatase 1B inhibitors
-
Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathway and has been validated as a therapeutic target for type 2 diabetes. A wide variety of scaffolds have been included in the structure of PTP1B inhibitors, one of them is the benzimidazole nucleus. Here, we report the design and synthesis of a new series of di- and tri- substituted benzimidazole derivatives including their kinetic and structural characterization as PTP1B inhibitors and hypoglycemic activity. Results show that compounds 43, 44, 45, and 46 are complete mixed type inhibitors with a Ki of 12.6 μM for the most potent (46). SAR type analysis indicates that a chloro substituent at position 6(5), a β-naphthyloxy at position 5(6), and a p-benzoic acid attached to the linker 2-thioacetamido at position 2 of the benzimidazole nucleus, was the best combination for PTP1B inhibition and hypoglycemic activity. In addition, molecular dynamics studies suggest that these compounds could be potential selective inhibitors from other PTPs such as its closest homologous TCPTP, SHP-1, SHP-2 and CDC25B. Therefore, the compounds reported here are good hits that provide structural, kinetic, and biological information that can be used to develop novel and selective PTP1B inhibitors based on benzimidazole scaffold.
- Campos-Almazán, Mara Ibeth,Flores-Ramos, Miguel,Hernández-Campos, Alicia,Castillo, Rafael,Sierra-Campos, Erick,Torgeson, Kristiane,Peti, Wolfgang,Valdez-Solana, Mónica,Oria-Hernández, Jesús,Méndez, Sara T.,Castillo-Villanueva, Adriana,Jiménez-de Jesús, Hugo,Avitia-Domínguez, Claudia,Téllez-Valencia, Alfredo
-
-
- Efficient nitriding reagent and application thereof
-
The invention discloses an efficient nitriding reagent and application thereof, wherein the nitriding reagent comprises nitrogen oxide, an active agent, a reducing agent and an organic solvent. By applying the nitriding reagent, nitrogen-containing compounds such as amide, nitrile and the like can be produced, and the method is simple in condition, low in waste discharge amount and simple in reaction equipment.
- -
-
Paragraph 0168-0171
(2021/03/31)
-
- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
-
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
- -
-
Paragraph 001137; 001138
(2021/01/22)
-
- Nitromethane as a nitrogen donor in Schmidt-type formation of amides and nitriles
-
The Schmidt reaction has been an efficient and widely used synthetic approach to amides and nitriles since its discovery in 1923. However, its application often entails the use of volatile, potentially explosive, and highly toxic azide reagents. Here, we report a sequence whereby triflic anhydride and formic and acetic acids activate the bulk chemical nitromethane to serve as a nitrogen donor in place of azides in Schmidt-like reactions. This protocol further expands the substrate scope to alkynes and simple alkyl benzenes for the preparation of amides and nitriles.
- Jiao, Ning,Liu, Jianzhong,Qiu, Xu,Song, Song,Wei, Jialiang,Wen, Xiaojin,Zhang, Cheng,Zhang, Ziyao
-
supporting information
p. 281 - 285
(2020/01/28)
-
- N-acetylation of amines in continuous-flow with acetonitrile—no need for hazardous and toxic carboxylic acid derivatives
-
A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.
- Fül?p, Ferenc,Mándity, István M.,Orsy, Gy?rgy
-
-
- GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
-
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
- -
-
Paragraph 001179; 001180; 001181
(2019/07/17)
-
- Transition-Metal-Free C-C, C-O, and C-N Cross-Couplings Enabled by Light
-
Transition-metal-catalyzed cross-couplings to construct C-C, C-O, and C-N bonds have revolutionized chemical science. Despite great achievements, these metal catalysts also raise certain issues including their high cost, requirement of specialized ligands, sensitivity to air and moisture, and so-called "transition-metal-residue issue". Complementary strategy, which does not rely on the well-established oxidative addition, transmetalation, and reductive elimination mechanistic paradigm, would potentially eliminate all of these metal-related issues. Herein, we show that aryl triflates can be coupled with potassium aryl trifluoroborates, aliphatic alcohols, and nitriles without the assistance of metal catalysts empowered by photoenergy. Control experiments reveal that among all common aryl electrophiles only aryl triflates are competent in these couplings whereas aryl iodides and bromides cannot serve as the coupling partners. DFT calculation reveals that once converted to the aryl radical cation, aryl triflate would be more favorable to ipso substitution. Fluorescence spectroscopy and cyclic voltammetry investigations suggest that the interaction between excited acetone and aryl triflate is essential to these couplings. The results in this report are anticipated to provide new opportunities to perform cross-couplings.
- Liu, Wenbo,Li, Jianbin,Querard, Pierre,Li, Chao-Jun
-
p. 6755 - 6764
(2019/05/06)
-
- Direct synthesis of N-arylamides via the coupling of aryl diazonium tetrafluoroborates and nitriles under transition-metal-free conditions
-
The direct synthesis of N-arylamides via the coupling of aryl diazonium tetrafluoroborates and nitriles under transition-metal-free conditions has been developed. The reported protocol is practical and represents an efficient method to produce functionalized amides in moderate to good yields.
- Xiong, Biquan,Wang, Gang,Xiong, Tao,Wan, Liming,Zhou, Congshan,Liu, Yu,Zhang, Panliang,Yang, Changan,Tang, Kewen
-
supporting information
p. 3139 - 3142
(2018/07/13)
-
- A to aryl diazonium tetrafluoroborate salts with a nitrile preparation machine acid radical amine compounds (by machine translation)
-
The invention provides a high-efficiency, high-selective synthesis of different substituted functional group containing organic amide compound, it adopts the cuprous iodide as a catalyst, in order to aryl diazonium tetrafluoroborate salts compounds and organic nitrile compound as the reaction substrate, the reaction system by adding the organic solvent, water and alkali. The advantage of this method: cheap and easily obtained catalyst; the substrate has a high applicability; mild reaction conditions, safe and reliable; the resulting target product selectivity is close to 100%, yield is as high as 90% or more. The method solves the traditional synthetic organic amide compound of rigorous reaction conditions, the reaction selectivity is poor, the experimental procedure is complicated, the productivity is low and needs to be used for the environment of a harmful reagent and the like, it has good industrial application prospect. The invention also provides a corresponding different substituted functional group containing organic amide compound. (by machine translation)
- -
-
Paragraph 0039
(2018/06/04)
-
- Eco-friendly, catalyst and solvent-free, synthesis of acetanilides and N-benzothiazole-2-yl-acetamides
-
An expeditious and green synthesis of acetamides in a solvent-free simple way is described, without catalyst or additives, and in good yield by an instantaneous reaction of anilines or 2-aminothiazoles and acetic anhydride without external heating, and with simple purification. Sixteen substituted acetanilides and four N-benzothiazole-2-yl-acetamides were formed, but aliphatic amines of low molecular weight were not as effective as aromatic ones, and only cyclohexylamine and the enaminone ethyl 3-amino-2-butenoate afforded the corresponding acetamides in good yield.
- Cunha, Silvio,De Santana, Louren?o L. B.
-
p. 1137 - 1144
(2017/05/01)
-
- Pd-Catalyzed C-H activation/oxidative cyclization of acetanilide with norbornene: Concise access to functionalized indolines
-
An efficient Pd-catalyzed oxidative cyclization reaction for the synthesis of functionalized indolines by direct C-H activation of acetanilide has been developed. The norbornylpalladium species formed via direct ortho C-H activation of acetanilides is supposed to be a key intermediate in this transformation. This journal is the Partner Organisations 2014.
- Gao, Yang,Huang, Yubing,Wu, Wanqing,Huang, Kefan,Jiang, Huanfeng
-
supporting information
p. 8370 - 8373
(2014/07/22)
-
- Reductive acylation of nitroarenes to anilides by sodium sulfite in carboxylic acids
-
A facile and efficient reductive acylation of aromatic nitro compounds to corresponding anilides using a sodium sulfite-carboxylic acid system for the first time has been reported. The sodium sulfite reagent provides the colorless reductant in combination with stoichiometric amounts of carboxylic acid and enables the formation of anilides from nitroarenes without any additives in good to excellent yields with high purities and simple work-up. Furthermore, this protocol provides a novel and complementary access to some industrially important chemicals in kilogram scale under mild conditions.
- Ghaffarzadeh, Mohammad,Akhavan, Pegah
-
supporting information
p. 1417 - 1419
(2016/09/28)
-
- A facile and efficient method for the selective deacylation of N-arylacetamides and 2-chloro-Narylacetamides catalyzed by SOCl2
-
Thionyl chloride efficiently and selectively promoted the deacylation of N-arylacetamides and 2-chloro-N-arylacetamides, under anhydrous conditions, without effecting the ester group, aminosulfonyl group, or benzyloxyamide group. This method, which has been successfully applied to a variety of substrates including different N-arylacetamides and 2-chloro-N-arylacetamides, has the attractive advantages of inexpensive reagents, satisfactory selectivity, excellent yields, short reaction time, and convenient workup. This new method can probably be used to selectively deacylate between aromatic amides and alkyl amides. Springer Science+Business Media B.V. 2011.
- Wang, Gong-Bao,Wang, Lin-Fa,Li, Chao-Zhang,Sun, Jing,Zhou, Guang-Ming,Yang, Da-Cheng
-
experimental part
p. 77 - 89
(2012/05/20)
-
- Exploration of the diketoacid integrase inhibitor chemotype leading to the discovery of the anilide-ketoacids chemotype
-
Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. A previous study of the diketoacid-based chemotype suggested that there are two aryl-binding domains on integrase. In this study, modifications to the indole-based diketoacid chemotype are explored. It is demonstrated that the indole group can be replaced with secondary but not tertiary (e.g., N-methyl) aniline-based amides without sacrificing in vitro inhibitory activity. The difference in activity between the secondary and tertiary amides is most likely due to the opposite conformational preferences of the amide bonds, s-trans for the secondary-amide and s-cis for the tertiary-amide. However, it was found that the conformational preference of the tertiary amide can be reversed by incorporating the amide nitrogen atom into an indoline heterocycle, resulting in very potent integrase inhibitors.
- Walker, Michael A.,Johnson, Timothy,Ma, Zhuping,Zhang, Yunhui,Banville, Jacques,Remillard, Roger,Plamondon, Serge,Pendri, Annapurna,Wong, Henry,Smith, Daniel,Torri, Albert,Samanta, Himadri,Lin, Zeyu,Deminie, Carol,Terry, Brian,Krystal, Mark,Meanwell, Nicholas
-
p. 5818 - 5821
(2007/10/03)
-
- A novel synthesis of N-arylamides from nitroarenes via reductive N-acylation with red phosphorus and iodine
-
A series of N-arylamides and imides were synthesized via reductive N-acylation of nitroarenes with red phosphorus and carboxylic acids, catalyzed by iodine or iodides; an I /I° redox cycle was proposed to promote the reaction. Georg Thieme Verlag Stuttgart.
- Du, Xiaohua,Zheng, Mei,Chen, Sheng,Xu, Zhenyuan
-
p. 1953 - 1955
(2008/02/08)
-
- Scope and selectivity in palladium-catalyzed directed C-H bond halogenation reactions
-
Palladium-catalyzed ligand directed C-H activation/halogenation reactions have been extensively explored. Both the nature of the?directing group and the substitution pattern on the arene ring of the substrate lead to different reactivity profiles, and often different and complementary products, in the presence and absence of the catalyst.
- Kalyani, Dipannita,Dick, Allison R.,Anani, Waseem Q.,Sanford, Melanie S.
-
p. 11483 - 11498
(2007/10/03)
-
- [Yb(OTf)3] catalysed facile conversion of ketoximes to amides and lactams
-
A variety of ketoximes undergo the Beckmann rearrangement upon a treatment with a catalytic amount of [Yb(OTf)3] in refluxing acetonitrile to afford the corresponding amides and lactams in excellent yields with high selectivity.
- Yadav,Reddy,Madhavi,Ganesh
-
p. 236 - 238
(2007/10/03)
-
- Promotion of the [PPN][Rh(CO)4]-catalysed carbonylation of nitrobenzene by 2-hydroxypyridine and related molecules: An apparent bifunctional activation
-
2-Hydroxypyridine and related molecules have a large activating effect on the previously reported [PPN][Rh(CO)4]-based catalytic system for the reductive carbonylation of nitrobenzene to methyl phenylcarbamate (PPN+=(PPh3)2N+). The effect is not due to the known 2-hydroxypyridine-2-pyridone tautomeric equilibrium, since 4-hydroxypyridine, for which the same tautomeric equilibrium exists, completely inhibits the reaction. A promoting effect of 2-hydroxypyridine is also observed in the reactions of a previously isolated metallacyclic complex, [PPN][Rh(CO)2ON(Ar)C(O)O], believed to be an intermediate in the catalytic reactions. However, the dependence of the rate of the catalytic reactions on the aniline concentration indicates that the effect found for the stoichiometric reaction cannot be the one that is relevant for the acceleration of the catalytic reactions. Thus, two different effects are present, both of which appear to be due to the proximal positions of a basic and an acidic site in the promoter molecules.
- Ragaini, Fabio,Gallo, Emma,Cenini, Sergio
-
p. 109 - 118
(2007/10/03)
-
- Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
-
Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy.Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy.The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells.Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and /or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells.Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced.Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxide have reduction potentials significantly more positive than Tirapazamine (Epc -0.90 V).The most potent cytotoxins to cells in culture were the 6,7-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine.The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity.Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro.In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine.This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
- Monge, Antonio,Palop, Juan A.,Cerain, Adela Lopez de,Senador, Virginia,Martinez-Crespo, Francisko J.,et al.
-
p. 1786 - 1792
(2007/10/02)
-
- Structure-Activity Studies on Amides Inhibiting Photosystem II
-
A series of N-phenylanilides and N-phenylureas have been synthesised and their 'in vitro' photosystem II activity measured in a cell-free system.An attempt was made to correlate 'in vitro' data with a novel hydrophobicity parameter ?amide (related to the substituent on the phenyl ring) and with the torsion angle θ between the planes of the phenyl and amide moieties.
- Lewis, Richard J.,Camilleri, Patrick,Kirby, Anthony J.,Marby, Craig A.,Slawin, Alexandra A.,Williams, David J.
-
p. 1625 - 1630
(2007/10/02)
-