- Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory
-
Alzheimer's disease (AD) is clearly linked to the decline of acetylcholine (ACh) effects in the brain. These effects are regulated by the hydrolytic action of acetylcholinesterase (AChE). Therefore, a central palliative treatment of AD is the administration of AChE inhibitors although additional mechanisms are currently described and tested for generating advantageous therapeutic strategies. In this work, we tested new arylamides and arylimides as potential inhibitors of AChE using in silico tools. Then, these compounds were tested in vitro, and two selected compounds, C7 and C8, as well as propranolol showed inhibition of AChE. In addition, they demonstrated an advantageous acute toxicity profile compared to that of galantamine as a reference AChE inhibitor. in vivo evaluation of memory performance enhancement was performed in an animal model of cognitive disturbance with each of these compounds and propranolol individually as well as each compound combined with propranolol. Memory improvement was observed in each case, but without a significant additive effect with the combinations.
- Ciprés-Flores, Fabiola J.,Farfán-García, Eunice D.,Andrade-Jorge, Erik,Cuevas-Hernández, Roberto I.,Tamay-Cach, Feliciano,Martínez-Archundia, Marlet,Trujillo-Ferrara, José G.,Soriano-Ursúa, Marvin A.
-
-
Read Online
- Application of maleimide compound as chitin synthase inhibitor
-
The invention discloses an application of a maleimide compound as shown in a formula I. In the formula I, R0 is phenyl, benzyl, phenethyl, phenylpropyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl,p-methoxyphenyl, p-methylphenyl or p-hydroxyphenyl, R1 is hydrogen, methyl, phenyl or chlorine; and R2 is hydrogen, methyl, phenyl or chlorine. The provided maleimide compound has a good inhibition effect on chitin synthase.
- -
-
Paragraph 0120-0123; 0124-0127
(2020/07/12)
-
- Redox-Selective Iron Catalysis for α-Amino C-H Bond Functionalization via Aerobic Oxidation
-
Single-electron oxidation and α-deprotonation of tertiary anilines using Fe(phen)3(PF6)3 afford α-aminoalkyl radicals, which can be coupled with electrophilic partners to afford various tetrahydroquinolines. Mechanistically, the Fe(phen)n 2+/3+ catalytic cycle is maintained by O2 or a TBHP oxidant, and the presence of the oxygen bound iron complex, Fe(III)-OO(H), was elucidated by electron paramagnetic resonance and electrospray ionization mass spectrometry. This redox-selective nonheme iron catalyst behaves similarly to bioinspired heme iron catalysts.
- Hwang, Joon Young,Ji, A. Young,Lee, Sang Hyeok,Kang, Eun Joo
-
supporting information
p. 16 - 21
(2019/11/11)
-
- Regioselective hydroarylation and arylation of maleimides with indazoles: Via a Rh(iii)-catalyzed C-H activation
-
Switchable Rh(iii)-catalyzed highly regioselective hydroarylation and oxidative arylation of maleimides with 2-arylindazoles via C-H activation have been demonstrated. The reaction affords 3-(2-(2H-indazol-2-yl)phenyl)succinimide and 3-(2-(2H-indazol-2-yl)phenyl)maleimide derivatives in high yields with wide functional group tolerance. A mechanistic study was performed to depict C-H bond cleavage that might be involved in the turnover limiting step.
- Ghosh, Asim Kumar,Samanta, Sadhanendu,Ghosh, Payel,Neogi, Sukanya,Hajra, Alakananda
-
supporting information
p. 3093 - 3097
(2020/05/08)
-
- Design, synthesis and biochemical evaluation of novel ethanoanthracenes and related compounds to target burkitt’s lymphoma
-
Lymphomas (cancers of the lymphatic system) account for 12% of malignant diseases worldwide. Burkitt’s lymphoma (BL) is a rare form of non-Hodgkin’s lymphoma in which the cancer starts in the immune B-cells. We report the synthesis and preliminary studies on the antiproliferative activity of a library of 9,10-dihydro-9,10-ethanoanthracene based compounds structurally related to the antidepressant drug maprotiline against BL cell lines MUTU-1 and DG- 75. Structural modifications were achieved by Diels-Alder reaction of the core 9-(2- nitrovinyl)anthracene with number of dienophiles including maleic anhydride, maleimides, acrylonitrile and benzyne. The antiproliferative activity of these compounds was evaluated in BL cell lines EBV? MUTU-1 and EBV+ DG-75 (chemoresistant). The most potent compounds 13j, 15, 16a, 16b, 16c, 16d and 19a displayed IC50 values in the range 0.17–0.38 μM against the BL cell line EBV? MUTU-1 and IC50 values in the range 0.45–0.78 μM against the chemoresistant BL cell line EBV+ DG- 75. Compounds 15, 16b and 16c demonstrated potent ROS dependent apoptotic effects on the BL cell lines which were superior to the control drug taxol and showed minimal cytotoxicity to peripheral blood mononuclear cells (PBMCs). The results suggest that this class of compounds merits further investigation as antiproliferative agents for BL.
- Byrne, Andrew J.,Bright, Sandra A.,McKeown, James P.,O’brien, John E.,Twamley, Brendan,Fayne, Darren,Williams, D. Clive,Meegan, Mary J.
-
-
- The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation
-
Adenylate cyclases (ACs), play a critical role in the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP). Studies have indicated that adenylyl cyclase type 2 (AC2) is potential drug target for many diseases, however, up to now, there is no AC2-selective agonist reported. In this research, docking-based virtual screening with the combination of cell-based biological assays have been performed for discovering novel potent and selective AC2 agonists. Virtual screening disclosed a novel hit compound 8 as an AC2 agonist with EC50 value of 8.10 μM on recombinant human hAC2 + HEK293 cells. The SAR (structure activity relationship) based on the derivatives of compound 8 was further explored on recombinant AC2 cells and compound 73 was found to be the most active agonist with the EC50 of 90 nM, which is 160-fold more potent than the reported agonist Forskolin and could selectively activate AC2 to inhibit the expression of Interleukin-6. The discovery of a new class of AC2-selective agonists would provide a novel chemical probe to study the physiological function of AC2.
- Li, Shanshan,Song, Gao,Wang, Liang-Liang,Weng, Zhiying,Xu, Guowei,Yang, Weimin,Yang, Yanming,Yang, Yaqing,Zhang, Jiajun,Zuo, Zhili
-
supporting information
(2020/02/27)
-
- Nickel(II) Tetraphenylporphyrin as an Efficient Photocatalyst Featuring Visible Light Promoted Dual Redox Activities
-
Nickel(II) tetraphenylporphyrin (NiTPP) is presented as a robust, cost-effective and efficient visible light induced photoredox catalyst. The ground state electrochemical data (CV) and electronic absorption (UV-Vis) spectra reveal the excited state redox potentials for [NiTPP]*/[NiTPP].? and NiTPP].+/[NiTPP]* couples as +1.17 V and ?1.57 V vs SCE respectively. The potential values represent NiTPP as a more potent photocatalyst compare to the well-explored [Ru(bpy)3]2+. The non-precious photocatalyst exhibits excited state redox reactions in dual fashions, i. e., it is capable of undergoing both oxidative as well as reductive quenching pathways. Such versatility of a photocatalyst based on first-row transition metals is very scarce. This unique phenomenon allows one to perform diverse types of redox reactions by employing a single catalyst. Two different sets of chemical reactions have been performed to represent the synthetic utility. The catalyst showed superior efficiency in both carbon-carbon and carbon-heteroatom bond-forming reactions. Thus, we believe that NiTPP is a valuable addition to the photocatalyst library and this study will lead to more practical synthetic applications of earth-abundant-metal-based photoredox catalysts. (Figure presented.).
- Mandal, Tanumoy,Das, Sanju,De Sarkar, Suman
-
supporting information
p. 3200 - 3209
(2019/05/16)
-
- Iron(III) Chloride/Phenylsilane-Mediated Cascade Reaction of Allyl Alcohols with Maleimides: Synthesis of Poly-Substituted γ-Butyrolactones
-
A iron-catalyzed free radical cascade reaction of allyl alcohols with N-substituted maleimides for accessing poly-substituted γ-butyrolactones has been developed. In this protocol, various allyl alcohols can open N-substituted maleimide rings to form allyl ester intermediates, and the allyl ester intermediates can be converted into an allyl ester alkyl radicals and undergo intramolecular free radical addition cyclization to form a polysubstituted γ-butyrolactones. In this protocol, spiro γ-butyrolactone compounds can be also synthesized. Meanwhile, the strategy could be applied to further construct a fully substituted tetrahydrofuran. The reaction is not sensitive to oxygen or moisture and has been performed on gram-scale. (Figure presented.).
- Zhang, Hua,Zhan, Xiao-Yu,Chen, Xu-Ling,Tang, Lei,He, Shuai,Shi, Zhi-Chuan,Wang, Yu,Wang, Ji-Yu
-
supporting information
p. 4919 - 4925
(2019/11/03)
-
- Amino Acid Salt Catalyzed Asymmetric Addition Reaction of Acetylacetone to Maleimides and 2-(2-Oxoindolin-3-ylidene)malononitriles
-
The exploration of catalytic potential of natural amino acid salt in activation of 1,3-dicarbonyls was carried out, in which maleimides and 2-(2-oxoindolin-3-ylidene)malononitriles were found to be good electrophiles and afforded the desired products with excellent yield and moderate optical purity. Control experiments showed that the secondary amino group of barium (S)-prolinate is critical to the catalytic activity as well as enantiocontrol, thus revealed an enamine activation mechanism is possible in the present methodology.
- Jiang, Jun,Li, Juan,Li, Xinhua,Liu, Hongxin,Wu, Haiyan,Xiao, Hong-Ping
-
supporting information
p. 1241 - 1245
(2019/06/08)
-
- Synthesis and biological evaluation of novel benzylidene-succinimide derivatives as noncytotoxic antiangiogenic inhibitors with anticolorectal cancer activity in vivo
-
A novel series of benzylidene-succinimide derivatives were synthesized, characterized and evaluated for their cytotoxicities against HCT116, and SW480 cancer cells and NCM460 normal human cells. Their antiangiogenic capabilities were evaluated using a chick chorioallantoic membrane (CAM) assay. The compound, XCF-37b, was selected as the most potent antiangiogenic inhibitor with noncytotoxicity to evaluate the pharmacological effects on human umbilical vein endothelial cells (HUVECs) and cancer cells in vivo and in vitro. The results showed that XCF-37b inhibited HT29-cell colon tumor growth in vivo, without showing cytotoxicity against the five other cancer cell lines in vitro. Experiments confirmed that XCF-37b had obvious antiangiogenic activity by HUVEC migration and invasion and rat aortic ring angiogenesis ex vivo. Mechanism studies showed that XCF-37b inhibited the AKT/mTOR and VEGFR2 signaling pathways, as evidenced by decreased expressions of phosphor-AKT (p-AKT), p-mTOR, p-VEGFR2 (Tyr175), p-Src (Tyr416), p-FAK (Tyr925), and p-Erk1/2 (Thr202/Tyr204). Moreover, XCF-37b significantly decreased the protein expressions of matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1α (HIF-1α). XCF-37b generally regulated angiogenic inhibition through several regulatory pathways, without significantly interfering with colorectal cancer cell growth.
- Luo, Kaixiu,Bao, Yafeng,Liu, Feifei,Xiao, Chuanfan,Li, Ke,Zhang, Conghai,Huang, Rong,Lin, Jun,Zhang, Jihong,Jin, Yi
-
p. 805 - 827
(2019/07/10)
-
- Alizarin red S-TiO2-catalyzed cascade C(sp3)-H to C(sp2)-H bond formation/cyclization reactions toward tetrahydroquinoline derivatives under visible light irradiation
-
A very low amount of organic dye (Alizarin red S) sensitized TiO2 and it was successfully used to catalyze cascade C(sp3)-H to C(sp2)-H bond formation/cyclization reactions under visible light irradiation. The modified TiO2 photocatalyst efficiently, for the first time, advanced [4+2] cyclization of N,N-dimethylanilines and maleimides to the corresponding tetrahydroquinolines in air atmosphere. The reaction proceeds through α-amino radicals without additional oxidant at ambient temperature to afford products in good to excellent yields.
- Hosseini-Sarvari, Mona,Koohgard, Mehdi,Firoozi, Somayeh,Mohajeri, Afshan,Tavakolian, Hosein
-
supporting information
p. 6880 - 6888
(2018/05/04)
-
- Catalyst and Additive-Free Diastereoselective 1,3-Dipolar Cycloaddition of Quinolinium Imides with Olefins, Maleimides, and Benzynes: Direct Access to Fused N,N′-Heterocycles with Promising Activity against a Drug-Resistant Malaria Parasite
-
A convenient and eco-friendly synthesis of various fused N-heterocyclic compounds through catalyst and additive-free 1,3 dipolar cycloadditions of quinolinium imides with olefins, maleimides, and benzynes in excellent yields and diastereoselectivities is reported. The thermally controlled diastereoselective [3 + 2] cycloaddition reaction between quinolinium imides and olefins provided cis-isomers at low temperature and trans-isomers at high temperature. A reaction between quinolinium imides with substituted maleimides gave four-ring-fused N-heterocyclic compounds in high yields as a single diastereomer. The aryne precursors also provided four-ring-fused N,N′-heterocyclic compounds in high yields. The in vitro antiplasmodial activity of selected molecules revealed that this class of molecules possesses potential for ongoing studies against malaria.
- Kumar, Rakesh,Chaudhary, Sandeep,Kumar, Rohit,Upadhyay, Pooja,Sahal, Dinkar,Sharma, Upendra
-
p. 11552 - 11570
(2018/09/25)
-
- Solvent-free and room temperature visible light-induced C-H activation: CdS as a highly efficient photo-induced reusable nano-catalyst for the C-H functionalization cyclization of: T -amines and C-C double and triple bonds
-
Nano-sized CdS was successfully prepared, fully characterized and applied as a highly efficient reusable photocatalyst for the synthesis of pyrrolo[3,4-c]quinolone and pyrrolo[2,1-a]isoquinoline-8-carboxylate derivatives through a condensation reaction of N,N-dimethylanilines or alkyl 2-(3,4-dihydroisoquinolin-2(1H)-yl)acetates with maleimides via a C-H activation approach under benign and eco-friendly conditions at room temperature without using any solvent and oxidant under visible light irradiation. Besides, the prepared photocatalyst has been successfully applied for the condensation reaction of N,N-dimethylanilines with alkyl but-2-ynedioates or phenyl acetylenes for the synthesis of novel 1,2-dihydroquinoline-3,4-dicarboxylate and aryl-1,2-dihydroquinoline derivatives for the first time. Using this method, all favourable products were obtained in good yields and relatively short reaction times under benign conditions with the application of visible light irradiation, a renewable energy source. The catalyst was easily recovered and reused several times without any loss of its activity.
- Firoozi, Somayeh,Hosseini-Sarvari, Mona,Koohgard, Mehdi
-
supporting information
p. 5540 - 5549
(2019/01/03)
-
- Synthesis and Evaluation of Novel Spiro[oxindole-isoxazolidine] Derivatives as Potent Antioxidants
-
The antioxidant activity of isatin derivatives can be described with the presence of enolic hydroxyl group at the second position of the ring because of the keto-enol tautomerism between NH and C O groups of indolone moiety. The reducing ability of the tested compounds was evaluated by their interaction with the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) at various concentrations. Novel spiro[oxindole-isoxazolidine] derivatives (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i) have been synthesized by 1,3-dipolar cycloaddition reactions of variously substituted maleimides (1) with isatin ketonitrone (3) and tested for their in vitro antioxidant potency in the DPPH assay. All the synthesized compounds have been identified as potent in vitro antioxidants.
- Kaur, Manpreet,Singh, Baldev,Singh, Baljit,Arjuna, Anania
-
p. 1348 - 1354
(2017/03/27)
-
- Improvement of thermal properties of poly(vinyl chloride) using chemical blending assisted ultrasonic technique
-
The thermal stabilization of poly(vinyl chloride) through blending techniques has been studied. Poly(vinyl chloride) was blended with modified polymer (cellulose acetate-diallyl amine) in different compositions to improve the thermal stability of poly(vinyl chloride). The thermal stability and morphology of the blend films were characterized by scanning electron microscope (SEM) and thermogravimetry. The results revealed that the presence of modified cellulose acetate improved the thermal stability of poly(vinyl chloride). This was attributed to the thermal stable diallylamine moieties among the cellulose acetate chains. The addition of traces of maleimide derivatives to poly(vinyl chloride) prior to the blend process led to an extra thermal stability of the blend film as shown from the values of the initial decomposition temperature (To) measured by thermogravimetry.
- Al-Ghamdi, Azza
-
p. 2285 - 2288
(2017/10/05)
-
- Photoorganocatalysed and visible light photoredox catalysed trifluoromethylation of olefins and (hetero)aromatics in batch and continuous flow
-
Trifluoromethylation of olefins and (hetero)aromatics with sodium triflinate as CF3 source and readily accessible benzophenone derivatives as photosensitisers has been developed in batch and flow. The use of an iridium-based photocatalyst enables the trifluoromethylation to proceed under visible light irradiation.
- Lefebvre, Quentin,Hoffmann, Norbert,Rueping, Magnus
-
supporting information
p. 2493 - 2496
(2016/02/18)
-
- 3-(6-bromo-4-oxy-4H-chromone)-1-phenyl-5-p-chlorphenyl-1,6a-dihydro pyrroline[3,4-c] pyrazole-4,6(3aH,5H)-diketone and preparation method and application thereof
-
The invention discloses 3-(6-bromo-4-oxy-4H-chromone)-1-phenyl-5-p-chlorphenyl-1,6a-dihydro pyrroline[3,4-c] pyrazole-4,6(3aH,5H)-diketone and a preparation method and application thereof. The preparation method comprises the steps that a chromone structure is introduced by adopting a 1,3-dipole cycloaddition method on the basis that a pentabasic pyrazole ring is introduced to N-p-chlorphenyl maleimide, and accordingly the novel 3-(6-bromo-4-oxy-4H-chromone)-1-phenyl-5-p-chlorphenyl-1,6a-dihydro pyrroline[3,4-c] pyrazole-4,6(3aH,5H)-diketone is synthesized. The compound has the good inhibiting effect on tumor cell lines, has better inhibition ratio and selectivity on leukemia cells and has a very good industrial application prospect on the aspects of preparation of anti-tumor drugs and the like.
- -
-
Paragraph 0015; 0029-0030
(2017/04/07)
-
- Potent Nematicidal Activity of Maleimide Derivatives on Meloidogyne incognita
-
Different maleimide derivatives were synthesized and assayed for their in vitro activity on the soil inhabiting, plant-parasitic nematode Meloidogyne incognita, also known as root-knot nematode. The compounds maleimide, N-ethylmaleimide, N-isopropylmaleimide, and N-isobutylmaleimide showed the strongest nematicidal activity on the second stage juveniles of the root-knot nematode with EC50/72h values of 2.6 ± 1.3, 5.1 ± 3.4, 16.2 ± 5.4, and 19.0 ± 9.0 mg/L, respectively. We also determined the nematicidal activity of copper sulfate, finding an EC50 value of 48.6 ± 29.8 mg/L. When maleimide at 1 mg/L was tested in combination with copper sulfate at 50 mg/L, we observed 100% mortality of the nematodes. We performed a GC-MS metabolomics analysis after treating nematodes with maleimide at 8 mg/L for 24 h. This analysis revealed altered fatty acids and diglyceride metabolites such as oleic acid, palmitic acid, and 1-monopalmitin. Our results suggest that maleimide may be used as a new interesting building block for developing new nematicides in combination with copper salts.
- Eloh, Kodjo,Demurtas, Monica,Mura, Manuel Giacomo,Deplano, Alessandro,Onnis, Valentina,Sasanelli, Nicola,Maxia, Andrea,Caboni, Pierluigi
-
p. 4876 - 4881
(2016/07/06)
-
- 1,3-dipolar cycloaddition reactions leading to the synthesis of new 2,3,5-triaryl-4h,2,3,3a,5,6,6a-hexahydropyrrolo[3,4-d]isoxazole-4,6-diones
-
Cycloaddition of C,N-diphenylnitrones 1 to N-aryl maleimides 2 afforded two diastereomeric isoxazolidines with high selectivity. The structure and steric configuration of the adducts have been assigned on the basis of 1H NMR, 1H NMR COSY, 13C NMR and IR spectroscopy. The π-π stacking interactions between maleimide's and nitrone's aromatic rings during the 1,3-dipolar cycloaddition were assumed to control the exo-endo selectivity of the reaction. Thus, the exo-endo ratio depends upon the position of the substituent present on the C-phenyl ring of the C,N-diphenylnitrones.
- Kaur, Anjandeep,Singh, Baldev
-
p. 1421 - 1429
(2015/04/27)
-
- One-pot regioselective synthesis of novel 1-N-methyl-spiro[2,3']oxindole-spiro[3,3"]-1"-N-arylpyrrolidine-2",5"-dione-4-arylpyrrolidines through multicomponent 1,3-dipolar cycloaddition reaction of azomethine ylide
-
An atom economic and facile synthesis of novel dispiro-oxindole-pyrrolidines has been achieved via a three-component tandem cycloaddition of azomethine ylide generated in situ from isatin and sarcosine by decarboxylative condensation with N-aryl-3-benzylidene-pyrrolidine-2,5-dione derivatives as dipolarophiles. The salient features of synthetic procedure are characterized by the mild reaction conditions, high yields, high regioselectivity and stereoselectivity, one-pot procedure, and operational simplicity. This regioselectivity was assumed to be under the influence of π-π stacking interactions between the aromatic rings of azomethine ylide and N-aryl-3-benzylidene-pyrrolidine-2,5-diones that further control the exo-endo selectivity of the reaction 1,3-dipolar cycloaddition. The regiochemistry and structures of the cycloadducts were determined with spectroscopic data.
- Kaur, Anjandeep,Kaur, Manpreet,Singh, Baldev
-
p. 827 - 833
(2015/05/13)
-
- DABCO-catalyzed [3+2] cycloaddition reactions of azomethine imines with N-aryl maleimides: Facile access to dinitrogen-fused heterocycles
-
DABCO-catalyzed [3+2] cycloaddition of azomethine imines with maleimides has been developed. This method could efficiently furnish dinitrogen-fused tetracyclic heterocycles in high levels of regioselectivity and with good yields.
- Jia, Qianfa,Chen, Lei,Yang, Gongming,Wang, Jian,Wei, Jia,Du, Zhiyun
-
supporting information
p. 7150 - 7153
(2015/12/12)
-
- Visible light mediated cyclization of tertiary anilines with maleimides using nickel(II) oxide surface-modified titanium dioxide catalyst
-
Surface-modified titanium dioxides by highly dispersed NiO particles have an extended absorption in the visible light region and a reduced hole-electron pair recombination than unmodified TiO2. They have now been successfully applied as highly active heterogeneous photocatalysts in the visible light mediated direct cyclization of tertiary anilines with maleimides to give tetrahydroquinoline products in moderate to high yields at ambient temperature. In contrast with unmodified titanium dioxide catalysts that are conventionally used in a stoichiometric amount in combination with UVA light, only a catalytic amount (1 mol %) of the surface-modified TiO2 catalyst is needed along with visible light to efficiently catalyze the reaction. Compared with transition-metal complexes such as Ru(bpy)3Cl2 or Ir(ppy)2(dtbbpy)PF6, advantages of these surface-modified titanium dioxides as photocatalyst include high catalytic activity, low cost, ease of recovering, and being able to be used for at least nine times without significant decay of catalytic activity.
- Tang, Jian,Grampp, Günter,Liu, Yun,Wang, Bing-Xiang,Tao, Fei-Fei,Wang, Li-Jun,Liang, Xue-Zheng,Xiao, Hui-Quan,Shen, Yong-Miao
-
supporting information
p. 2724 - 2732
(2015/03/18)
-
- Synthesis and biological evaluation of novel N-aryl maleimide derivatives clubbed with α-hydroxyphosphonates
-
A series of novel molecules 5a-g containing N-aryl maleimide and α-hydroxyphosphonate moieties were synthesized. A distinct approach for high-yielding synthesis of α-hydroxyphosphonates has been discovered using various catalyst and solvents. The structures of the synthesized compounds were elucidated by IR, NMR, MS and CHN analysis. All the synthesized compounds were tested for qualitative (Zone of inhibition) and quantitative (MIC) antimicrobial activities against two pathogenic bacteria such as Bacillus subtilis (NCIM 2250) and Escherichia coli (ATCC 25922) and four pathogenic fungi such as Candida albicans (MTCC 277), Candida tropicalis (MTCC184), Aspergillus niger (MCIM 545) and Aspergillus clavatus (MTCC 132). The investigation of antimicrobial screening data revealed that most of the tested compounds are moderate to good microbial inhibitors.
- Patil, Nilesh S.,Deshmukh, Ganesh B.,Patil, Sambhaji V.,Bholay, Avinash D.,Gaikwad, Nitin D.
-
p. 490 - 497
(2014/07/21)
-
- An expeditious synthesis of imides from phthalic, maleic and succinic anhydrides and chemoselective C=C reduction of maleic amide esters
-
Phthalic, maleic and succinic anhydrides have been reacted with aromatic amines to obtain the corresponding monoacid monoamides. The latter have been each transformed into the corresponding cyclic imide derivatives by treating with SOCl2. Alternatively, anhydrides have been reacted with methanolic KOH to obtain monomethyl ester derivatives which on reaction with aromatic amines in the presence of EDC. HCl and HOBt give cyclic imide derivatives. Reaction of monoacid monoamides independently, with SOCl 2 at 0-5°C give the monoamide monoester derivatives. Treatment of monoamide monoester of malic anhydride with NaBH4 leads to the unusual reduction of C=C grouping as well as the carbonyl group of the ester group to from monoamide monoalcohol of succinic anhydride. Preparation of monoamide monoalcohol of succinic anhydride can also be achieved by chemoselective reduction of monoamide monoester of malic anhydride with Mg turnings yielding monoamide monoester of succinic anhydride followed by reduction of the latter with NaBH4.
- Kumar, Padam Praveen,Reddy, Y. Dathu,Kumari, Y. Bharathi,Devi, B. Rama,Dubey
-
p. 392 - 398
(2014/05/06)
-
- A facile and green synthesis of N-substituted imides
-
Anhydrides 1, 6 and 10 have been reacted, independently, with aromatic primary amines 2 in solid phase by simple physical grinding of reactants with p-toluenesulphonicacid as a catalyst to yield corresponding open chain derivatives, monoacid monoamides3,7 and 11 respectively. The latter have each been transformed into the corresponding cyclic derivatives, i.e. imides 5, 9 and 13 respectively in solid phase by simple physical grinding of each with K 2CO3, alkylating agent and tetrabutylammoniumbromide as a catalyst with short reaction times. These cyclic imides can also be obtained by physical grinding of each of 3, 7 and 11 with dicyclohexylcarbodimide as a dehydrating agent in solid phase.
- Kumar, Padam Praveen,Rama Devi,Dubey
-
p. 1166 - 1171
(2013/09/24)
-
- Studies on reactions of anhydrides with Schiff bases
-
Reaction of phthalic anhydride 1 with benzylidineanilines 2, in equimolar ratio in hot acetic acid, yields N-arylphthalimides 3. Compound 1 reacts with the arylimine part of the Schiff base eliminating benzaldehyde part 4 as the bye-product. This reaction of 1 with 2 is also found to occur with other anhydrides like succinic anhydride 5, maleic anhydride 7 and acetic anhydride 9 resulting in the formation of the corresponding N-arylimides, namely, succinicimide 6, maleicimide 8 and aceticimide 10 respectively. In all the above reactions, the by-product, i.e. benzaldehyde or p-chlorobenzaldehyde can be isolated and characterized as its 2,4-dinitrophenylhydrazone derivative. Probable mechanism for the formation of imides from the corresponding anhydrides and Schiff bases has been suggested.
- Kumar, Padam Praveen,Mohiuddin,Rama Devi,Dubey
-
p. 686 - 690
(2013/07/11)
-
- Substituent effects on the regioselectivity of maleamic acid formation and hydrogen chloride addition to N-aryl maleimides
-
Itaconic anhydride reacts with aryl amines to give a substituent controlled equilibrium mixture of regioisomeric (Z)-2-methyl- and (Z)-3-methyl-4-oxo-4- (arylamino)but-2-enoic acids. Electron-donating groups favor nucleophilic attack on C-5 carbonyl, while the presence of electron-withdrawing groups enhances the bias for attack on C-2 carbonyl. The treatment of (Z)-2-methyl- and (Z)-3-methyl-4-oxo-4-(arylamino)but-2-enoic acids with SOCl2-Et 3N in THF provided the corresponding maleimides in high yields while under the same conditions the maleic anhydride aryl amine addition products gave predominately the corresponding 3-chloro-1-arylpyrrolidine-2,5-diones and maleimides in substituent dependent ratio. TUeBITAK, 2012.
- Faturaci, Yeliz,Coskun, Necdet
-
p. 749 - 758
(2013/02/25)
-
- Reaction on water: A greener approach for the thia michael addition on N-Aryl maleimides
-
A greener, economical, and efficient methodology for the Michael addition of thiols to N-aryl maleimides has been developed.
- Kumar, Varun,Mitra, Rangan,Bhattarai, Sanjay,Nair, Vipin A.
-
body text
p. 392 - 404
(2011/04/15)
-
- Antifungal, cytotoxic and SAR studies of a series of N-alkyl, N-aryl and N-alkylphenyl-1,4-pyrrolediones and related compounds
-
The synthesis, in vitro evaluation and SAR studies of 67 maleimides and derivatives acting as antifungal agents are reported. A detailed SAR study supported by theoretical calculations led us to determine that: an intact maleimido ring appears to be necessary for a strong antifungal activity, dissimilarly affected by the substituents in positions 2 and 3. The best activities were shown by 2,3-nonsubstituted followed by 2,3 dichloro- and 2-methyl-substituted maleimides. They all were fungicide rather than fungistatic enhancing the importance of their antifungal activity. 2,3-Dimethyl and 2,3-diphenyl-maleimides possessed marginal or null activity. The presence of a flexible connecting chain in N-phenylalkyl maleimides appears not to be essential for antifungal activity, although its length shows a correlation with the antifungal behavior, displaying maleimides with alkyl chains of n = 3 and n = 4 the best antifungal activities in most fungi. Different substituents on the benzene ring did not have a clear influence on the activity. Values of chemical potential properties as well as of energy do not sufficiently discriminate between active and inactive compounds. Nevertheless, it was found that, although log P alone is not strong enough to properly predict the antifungal activity, the comparison of its values for compounds within the same sub-type, showed an enhancement of antifungal activity along with an increment of lipophilicity. In addition, the LUMO's electronic clouds of the highly active compounds showed to be concentrated on the imido ring, indicating that their carbon atoms are potential sites for nucleophilic attack. Same results were obtained from MEPs. Most of the active compounds did not show cytotoxic activity against human cancer cell lines and no one possessed hemolytic activity, indicating that their activity is selective to pathogenic fungi and that they are not toxic at MIC concentrations.
- Sortino,Garibotto,Cechinel Filho,Gupta,Enriz,Zacchino
-
experimental part
p. 2823 - 2834
(2011/06/21)
-
- Microwave-assisted synthesis and structure-activity relationships of neuroactive pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives
-
We described herein the optimization of the synthetic methodology exploited to obtain the pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine sedative prototype 1a and novel analogues designed by successive molecular simplifications. By applying microwave irradiation during the hetero Diels-Alder key-step to obtain the heterotricyclic scaffold, under solvent-free conditions, we were able to obtain the desired compounds in drastically shorter times and better yields. Additionally, in vivo evaluation of the sedative effects of these heterocyclic derivatives showed that 1a and the novel structurally-related analogue 1e were the most efficient compounds to impair the locomotor activity in mice at the dose of 10 μmol/kg.
- Nascimento-Junior, Nailton M.,Mendes, Thaiana C.F.,Leal, Daniella M.,Correa, Claudia Maria N.,Sudo, Roberto T.,Zapata-Sudo, Gisele,Barreiro, Eliezer J.,Fraga, Carlos A.M.
-
supporting information; experimental part
p. 74 - 77
(2010/03/30)
-
- Discovery and structural optimization of pyrazole derivatives as novel inhibitors of Cdc25B
-
Structural optimization and preliminary structure-activity relationship studies of a series of N-substituted maleimide fused-pyrazole analogues with Cdc25B inhibitory activity, starting from a high-throughput screening hit, are illustrated. A simplified 3,5-diacyl pyrazole analogue was obtained as the most potent compound (118, IC50 = 0.12 μM) with a 270-fold increase in potency.
- Chen, Hai-Jun,Liu, Yong,Wang, Li-Na,Shen, Qiang,Li, Jia,Nan, Fa-Jun
-
scheme or table
p. 2876 - 2879
(2010/07/04)
-
- Derivatives of aryl amines containing the cytotoxic 1,4-dioxo-2-butenyl pharmacophore
-
Several series of compounds containing the 1,4-dioxo-2-butenyl moiety have been prepared as candidate cytotoxins, including the methyl N-arylmaleamates, methyl N-arylfumaramates, and N-arylmaleimides. In addition, the N-arylisomaleimides were synthesized which are the structural isomers of N-arylmaleimides. These compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. Methyl N-arylfumaramates showed the highest cytotoxic potencies and, in particular, methyl N-(3,4-dichlorophenyl)fumaramate is six times more potent than melphalan towards L1210 cells and is equipotent with this drug in the Molt 4/C8 assay. Electrophilicity of compounds under investigation was demonstrated by carrying out thiolation using model benzyl mercaptan on representative compounds. Methyl N-(3,4-dichlorophenyl)fumaramate and methyl N-(4-chlorophenyl)maleamate inhibited human N-myristoyltransferase, a possible molecular target, in high micromolar range. QSAR and molecular modeling revealed some correlations between different structural features of a number of the molecules and cytotoxic potencies. Methyl N-arylfumaramates were well tolerated in mice in comparison to the analogs in other series of compounds tested. The data obtained in this investigation affords guidelines for preparing new series of molecules with greater potencies.
- Jha, Amitabh,Mukherjee, Chandrani,Prasad, Ashok K.,Parmar, Virinder S.,Vadaparti, Manjula,Das, Umashankar,De Clercq, Erik,Balzarini, Jan,Stables, James P.,Shrivastav, Anuraag,Sharma, Rajendra K.,Dimmock, Jonathan R.
-
experimental part
p. 1510 - 1515
(2010/06/16)
-
- Bicyclic guanidine-catalyzed direct asymmetric allylic addition of N-aryl alkylidene-succinimides
-
Enantio-enriched maleimides and succinimides that can be used to prepare aza-heterocycles with multiple chiral centers are obtained from the bicyclic guanidine-catalyzed direct asymmetric allylic addition of N-aryl alkylidene-succinimides to imines. NMR studies and deuterium-exchange experiments were used to study the intermediates in the reaction.
- Wang, Jianmin,Liu, Hongjun,Fan, Yitian,Yang, Yuanyong,Jiang, Zhiyong,Tan, Choon-Hong
-
supporting information; experimental part
p. 12534 - 12537
(2011/02/22)
-
- Access to indoles via Diels-Alder reactions of 2-vinylpyrroles with maleimides
-
(Chemical Equation Presented) Variously substituted 2-vinylpyrroles underwent an endo-addition [4+2] cycloaddition reaction with maleimides followed by a spontaneous highly diastereoselective (93-98% de) isomerization to give tetrahydroindoles in moderate to excellent yield. Treatment with activated MnO2 in refluxing toluene provided the corresponding indoles in moderate to good yield. This highly convergent methodology for formation of indoles is versatile and the starting materials are conveniently prepared.
- Noland, Wayland E.,Lanzatella, Nicholas P.,Venkatraman, Lakshmanan,Anderson, Nicholas F.,Gullickson, Glen C.
-
experimental part
p. 1154 - 1176
(2010/03/04)
-
- Synthesis and in vitro evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitors
-
The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have been described so far. Here, we describe the synthesis of N-substituted maleimides and their pharmacological evaluation on the recombinant human fatty acid amide hydrolase (FAAH) and on the purified human MGL. A few N-arylmaleimides were previously described (Saario, S. M.; Salo, O. M.; Nevalainen, T.; Poso, A.; Laitinen, J. T.; Jarvinen, T.; Niemi, R. Characterization of the Sulfhydryl-Sensitive Site in the Enzyme Responsible for Hydrolysis of 2-Arachidonoylglycerol in Rat Cerebellar Membranes. Chem. Biol. 2005, 12, 649-656) as MGL inhibitors, and along these lines, we present a new set of maleimide derivatives that showed low micromolar IC50 and high selectivity toward MGL vs FAAH. Then, structure-activity relationships have been investigated and, for instance, 1-biphenyl-4-ylmethylmaleimide inhibits MGL with an IC50 value of 790 nM. Furthermore, rapid dilution experiments reveal that these compounds act as irreversible inhibitors. In conclusion, N-substituted maleimides constitute a promising class of potent and selective MGL inhibitors.
- Matuszak, Nicolas,Muccioli, Giulio G.,Labar, Geoffray,Lambert, Didier M.
-
experimental part
p. 7410 - 7420
(2010/04/30)
-
- Substituent chemical shifts of N-arylsuccinanilic acids, N-arylsuccinimides, N-arylmaleanilic acids, and N-arylmaleimides
-
NMR spectra of a series of N-arylsuccinanilic acids, N-arylsuccinimides, N-arylmaleanilic acids, and N-arylmaleimides were examined to estimate the electronic effect of the amide and imide groups on the chemical shifts of the hydrogen and carbon nuclei of the benzene ring.
- Lee, Hye Sun,Yu, Ji Sook,Lee, Chang Kiu
-
scheme or table
p. 711 - 715
(2010/07/05)
-
- Design and synthesis of a novel DNA-encoded chemical library using Diels-Alder cycloadditions
-
DNA-encoded chemical libraries are increasingly being employed for the identification of binding molecules to protein targets of pharmaceutical relevance. Here, we describe the synthesis and characterization of a DNA-encoded chemical library, consisting of 4000 compounds generated by Diels-Alder cycloaddition reactions. The compounds were encoded with unique DNA fragments which were generated through a stepwise assembly process and serve as amplifiable bar codes for the identification and relative quantification of library members.
- Buller, Fabian,Mannocci, Luca,Zhang, Yixin,Dumelin, Christoph E.,Scheuermann, Joerg,Neri, Dario
-
supporting information; experimental part
p. 5926 - 5931
(2009/05/31)
-
- Dicarboxamide derivatives
-
The invention is concerned with novel dicarboxamide derivatives of formula (I) wherein A, B, Rc, D and E are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the coagulation factor Xa and can be used as medicaments.
- -
-
Page/Page column 42
(2008/06/13)
-
- α-chlorosuccinimides - A new source for maleimides and succinimides
-
N-Arylmaleimides and N-arylsuccinimides were prepared by dehydrochlorination reaction of N-aryl α-chlorosuccinimides in the presence of a base and by reduction of 2-chlorosuccinimide in the presence of zinc, respectively. N-Aryl α-chlorosuccinimides were obtained by dehydration of N-aryl substituted maleamic acids in the presence of thionyl chloride. The structure of the synthesized compounds was confirmed by IR, 1H-NMR and 13C-NMR spectra.
- Gǎinǎ, Constantin,Gǎinǎ, Viorica
-
p. 655 - 661
(2007/10/03)
-
- In vitro antifungal properties, structure-activity relationships and studies on the mode of action of N-phenyl, N-aryl, N-phenylalkyl maleimides and related compounds
-
The synthesis, in vitro antifungal evaluation and structure-activity relationship studies of 14 compounds of the N-phenyl-, N-aryl-, N-phenylalkyl- maleimide and 3,4-dichloromaleimide series are reported. The compounds were evaluated against a panel of standardized yeasts and filamentous fungi as well as clinical isolates of Candida albicans. The activities of N-phenylalkyl-3,4- dichloromaleimide derivatives but not those of N-phenylalkyl-maleimide derivatives showed to be dependent on the length of the alkyl chain. N-Phenylpropyl-3,4-dichloromaleimide showed the broadest spectrum of action and lower minimal inhibitory concentrations (MIC) in all of the fungi tested. The nitrogen-carbon distance between the two rings seems to play an important role in the antifungal behavior of these compounds. The most active structure showed inhibited (1,3)β-D-glucan and chitin synthases, enzymes that catalyze the synthesis of the major fungal cell-wall polymers. ECV · Editio Cantor Verlag, Aulendorf (Germany).
- Lopez, Silvia N.,Castelli, Maria V.,De Campos, Fatima,Correa, Rogerio,Cechinel Filho, Valdir,Yunes, Rosendo A.,Zamora, Miguel A.,Enriz, Ricardo D.,Ribas, Juan C.,Furlan, Ricardo L. E.,Zacchino, Susana A.
-
p. 123 - 132
(2007/10/03)
-
- Synthesis and antimicrobial activity of some succinimides
-
A series of substituted succinimides 3 are prepared from hydrazides and maleimides. The compounds are characterized and screened for their antimicrobial activities.
- Shetgiri,Nayak
-
p. 1933 - 1936
(2007/10/03)
-
- Synthesis and characterization of new compounds containing 1,4-dithiintetracarboxydiimide units
-
New compounds containing 1,4-dithiintetracarboxydiimide units were synthesized by the disubstitution reaction of N-substituted 2,3- dichloromaleimide with sodium sulflde nonahydrate or thiourea. IR, UV-vis and 1H-NMR spectroscopy, as well as elemental analysis, confirmed their structures. Thermal conversion of 1,4-dithiine ring to thiophene was monitored by differential calorimetry (DSC) and thermogravimetric (TGA) measurements.
- Gǎinǎ, Constantin
-
p. 601 - 607
(2007/10/03)
-
- Organic reactions in ionic liquids: Ionic liquid-promoted efficient synthesis of N-alkyl and N-arylimides
-
In the ionic liquids [Bmim][PF6] or [Bmim][BF4], a series of succinimide, maleimide and phthalimide derivatives were synthesized from corresponding anhydrides with a variety of primary amines in excellent yield.
- Le, Zhang-Gao,Chen, Zhen-Chu,Hu, Yi,Zheng, Qin-Guo
-
p. 995 - 998
(2007/10/03)
-
- Investigation of arene-arene interaction in stereoselective MCPBA epoxidation
-
Effect of arene-arene interaction in stereoselective MCPBA epoxidation was investigated using 5,6-dimethyl-2-phenyl-3a,4,7,7a-tetrahydroisoindole-1,3-diones 1. From the good correlation between the stereoselectivity of the products and Hammett's coefficients of para-substituents (σP) on the phenyl group, it was found that polar/π interaction between the phenyl group and MCPBA is the main interaction for controlling the stereoselectivity in the reaction. Other arene-arene interactions, charge-transfer complexation and edge-to-face interaction, were assumed to be much weaker than polar/π interaction in this reaction.
- Kishikawa, Keiki,Naruse, Mamoru,Kohmoto, Shigeo,Yamamoto, Makoto,Yamaguchi, Kentaro
-
p. 462 - 468
(2007/10/03)
-
- CHLOROSULFONATION OF N-ARYLMALEIMIDES
-
N-Phenylmaleimides, o-, m- and p-substituted (1) react with excess chlorosulfonic acid to give the corresponding sulphonyl chlorides (2-5).These were condensed with amines and phenols to give derivatives (7-29) which underwent hydrolysis or ammonolysis to give respectively the sulfamoyl maleamic acids (31-34) and sulfamoyl maleamides (35-39). Key words: N-arylmaleimides; chlorosulfonation
- Tome, Augusto C.,Cavaleiro, Jose A. S.,Domingues, Fernando M. J.,Cremlyn, Richard J.
-
p. 187 - 194
(2007/10/02)
-
- Process for preparation of N-substituted maleimides
-
N-substituted maleimide represented by formula (2): STR1 is produced from N-substituted maleamic acid monoester represented by formula (1): STR2 in the presence of an acid catalyst by elmination of an alcohol from the monoester. The above N-substituted maleamic acid monoester represented by formula (1) is produced by esterification of N-substituted maleamic acid represented by formula (3): STR3 with an alcohol R2 -OH in the represence of an acid catalyst.
- -
-
-
- Thermal Cycloaddition of N-Arylmaleimides to Phenols: the Convenient Synthesis of Bicyclooct-2-en-5-one and Tricyclo2,8>octan-2-one Derivatives from Phenols
-
Monohydric phenols undergo 2,5-thermal cycloaddition of N-substituted maleimides to give bicyclooct-2-en-5-ones.Homopolymers of the maleimides are also concurrently formed, except in the case of N-(2,6-dimethylphenyl)maleimide: this is the preferred addend and gave a 63percent yield of the 2,5-adduct as a mixture of exo and endo isomers.U.v. irradiation in acetone of the diester (16) derived from the endo adduct of phenol and N-phenylmaleimide gave the tricyclo2,8>octan-3-one (17) in quantitative yield.
- Bryce-Smith, Derek,Gilbert, Andrew,McColl, Ian S.,Drew, Michael G. B.,Yianni, Paul
-
p. 1147 - 1152
(2007/10/02)
-
- Diels-Alder Reaction: 1,4-Cycloaddition of N-Aryl-maleimides to Alkylidene- and Arylidene-fluorenones and Synthesis of Some New Fluoranthene Derivatives
-
The 1,4-cycloaddition of different N-arylmaleimides (IIa-f) to alkylidene- and arylidene-fluorenones (Ia-c) leads to the formation of the diadducts, 7-substituted-5-aryl-4,6-dioxo-4H-3,3a,5,6,6a,7,10b-octahydrofluoranthenopyrrole-endo(3,10b)-N-arylpyrrolidino-2',5'-diones (IIIa-r).The fully aromatized fluoranthene derivatives (Va-i) have also been synthesised either by boiling III in nitrobenzene or by reacting the bromo-derivatives (V) with appropriate II.Reduction of III using LAH gives VIII.The structures of the isolated products have been confirmed by elemental analyses, molecular weight determination and spectroscopic data.
- Abdou, Sadek E.,Habashy, Adiba,Aziz, Gamil,Khalifa, Fathy
-
p. 755 - 758
(2007/10/02)
-