- O-Alkyl Hydroxamates Display Potent and Selective Antileishmanial Activity
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Leishmania (L.) infantum causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that O-alkyl hydroxamate derivatives displayed potent and selective in vitro activity against the amastigote stage of L. infantum while no activity was observed against promastigotes. Compound 5 showed potent in vivo activity against L. infantum. Moreover, the combination of compound 5 supported on gold nanoparticles and meglumine antimoniate was also effective in vivo and improved the activity of these compounds compared to that of the individual treatment. Docking studies showed that compound 5 did not reach highly conserved pocket C and established interactions with the semiconserved residues V44, A45, R242, and E243 in pocket A of LiSIR2rp1. The surface space determined by these four amino acids is not conserved in human sirtuins. Compound 5 represents a new class of selective ligands with antileishmanial activity.
- Corpas-López, Victoriano,Tabraue-Chávez, Mavys,Sixto-López, Yudibeth,Panadero-Fajardo, Sonia,Alves De Lima Franco, Fernando,Domínguez-Seglar, José F.,Morillas-Márquez, Francisco,Franco-Montalbán, Francisco,Díaz-Gavilán, Mónica,Correa-Basurto, José,López-Viota, Julián,López-Viota, Margarita,Pérez Del Palacio, José,De La Cruz, Mercedes,De Pedro, Nuria,Martín-Sánchez, Joaquina,Gómez-Vidal, José A.
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- Lappaconitine derivative with analgesic activity, and preparation method and application thereof
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The invention provides a lappaconitine derivative with analgesic activity, and a preparation method and application thereof. The structure of the lappaconitine derivative is as shown in formula I in the specification. The lappaconitine derivative provided by the invention is high in analgesic activity, good in water solubility and low in biotoxicity, can be used for preparing low-toxicity analgesic drugs, and is wide in application prospect.
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Paragraph 0341-0345
(2021/07/14)
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- Ni-Catalyzed Direct Carboxylation of Aryl C?H Bonds in Benzamides with CO2
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The direct carboxylation of inert aryl C?H bond catalyzed by abundant and cheap nickel is still facing challenge. Herein, we report the Ni-catalyzed direct carboxylation of aryl C?H bonds in benzamides under 1 atm of CO2 to afford various methyl carboxylates or phthalimides, dealing with different post-processing. The reaction displays excellent functional group tolerance and affords moderate to high carboxylation yields under mild conditions. Detail mechanistic studies suggest that a Ni(0)?Ni(II)?Ni(I) catalytic cycle may be involved in this reaction. (Figure presented.).
- Li, Bin,Pei, Chunzhe,Wang, Baiquan,Zong, Jiarui
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supporting information
(2021/12/08)
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- Synthesis and molecular docking studies of some novel antimicrobial benzamides
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Common use of classical antibiotics has caused to the growing emergence of many resistant strains of pathogenic bacteria. Therefore, we aimed to synthesize a number of N-(2-hydroxy-(4 or 5)-nitrophenyl)benzamide derivatives as a new class of antimicrobial compounds. Moreover, our second goal is to predict the interaction between active structures and enzymes (DNA –gyrase and FtsA) in the binding mode. In this study, thirteen N-(2-hydroxy-(4 or 5-nitrophenyl)-substituted-benzamides were synthesized and determined for their antimicrobial activity using the microdilution method. According to this work, none of the compounds showed any activity against Candida albicans and its clinical isolate. Some of the benzamides (4N1, 5N1, 5N2) displayed very significant activity against Staphylococcus aureus and MSSA with 4 μg/ml MIC value, even they were found to be more potent than ceftazidime. 4N1 was also found to be more effective than gentamicin against Enterococcus faecalis clinical isolate. Molecular docking studies revealed that 4N1, 5N1, and 5N2 showed a good interactions with DNA-gyrase. Moreover, 5N1 has interacted with FtsA enzyme in the binding mode, as well. Only compound 5N4 displayed very good activity against Escherichia coli ATCC 25922. These findings showed us that 4N1, 5N1, 5N2, and 5N4 could be lead compounds to discover new antibacterial candidates against multidrug-resistant strains.
- Acar, Cemre,Yal??n, Gozde,Ertan-Bolelli, Tu?ba,Kaynak Onurda?, Fatma,?kten, Suzan,?ener, Funda,Y?ld?z, ?lkay
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- Myobacterium Tuberculosis-Thioredoxin Reductase Inhibitor as an Antitubercular Agent
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The invention relates to Mycobacterium tuberculosis-thioredoxin reductase inhibitors, processes for the preparation thereof, drugs containing said compounds, and the use of said compounds for manufacturing drugs.
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Paragraph 0103; 0112
(2020/05/06)
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- 4-butyl polyhydroxy benzophenone compound derivative and application thereof
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The invention belongs to the field of medicines, and particularly relates to a 4-butyl polyhydroxy benzophenone compound derivative which is used as a medicine for preventing and treating oxidative stress injury, reducing blood fat and protecting liver. The chemical general formula of the derivative is described in the specification, wherein R1 is selected from n-butyl, isobutyl or tert-butyl, R2is selected from hydrogen, hydroxyl or halogen, R3 is selected from hydrogen, hydroxyl or carboxylic ester, R4 is selected from hydrogen, hydroxyl or carboxylic ester, R5 is selected from hydrogen orhydroxyl, and R6 is selected from hydrogen, hydroxyl or halogen. According to the 4-butyl polyhydroxy benzophenone compound derivative provided by the invention, the protection rate of most compoundson injured cells is higher than 90%, and the antioxidant activity and the protection rate on the injured cells are remarkably different from those of natural animal and plant extracts applied to the market at present. The 4-butyl polyhydroxy benzophenone compound derivative provided by the invention has a remarkable liver protection effect, not only has an inhibition effect on adipogenesis, but also has a remarkable improvement effect on liver injury caused by NAFLD.
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Paragraph 0046-0049
(2020/07/21)
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- Identification of Anti-Mycobacterial Biofilm Agents Based on the 2-Aminoimidazole Scaffold
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Tuberculosis (TB) remains a significant global health problem for which new therapeutic options are sorely needed. The ability of the causative agent, Mycobacterium tuberculosis, to reside within host macrophages and form biofilm-like communities contributes to the persistent and drug-tolerant nature of the disease. Compounds that can prevent or reverse the biofilm-like phenotype have the potential to serve alongside TB antibiotics to overcome this tolerance, and decrease treatment duration. Using Mycobacterium smegmatis as a surrogate organism, we report the identification of two new 2-aminoimidazole compounds that inhibit and disperse mycobacterial biofilms, work synergistically with isoniazid and rifampicin to eradicate preformed M. smegmatis biofilms in vitro, are nontoxic toward Galleria mellonella, and exhibit stability in mouse plasma.
- Nguyen, T. Vu,Minrovic, Bradley M.,Melander, Roberta J.,Melander, Christian
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p. 927 - 937
(2019/03/26)
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- 4-n-butyl benzoyl chloride synthesis method
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The invention discloses a 4-n-butyl benzoyl chloride synthesis method. The 4-n-butyl benzoyl chloride synthesis method comprises the following steps: (1) taking dibenzoyl peroxide as a catalyst and triethanolamine as an auxiliary catalyst, enabling 4-n-butyl methylbenzene and chlorine to have a chlorination to prepare a crude product of 4-n-butyl trichlorotoluene; and (2) enabling the crude product of 4-n-butyl trichlorotoluene and 4-n-butyl benzoic acid to have an acylation reaction with the participation of a catalyst ferric trichloride to prepare a target product 4-n-butyl benzoyl chloride.The fuming material oxalyl chloride is not needed, chlorine is introduced into the 4-n-butyl methylbenzene to generate 4-n-butyl trichlorotoluene, the 4-n-butyl trichlorotoluene and the 4-n-butyl benzoic acid are then reacted to generate the 4-n-butyl benzoyl chloride, the reaction operation is safe and simple, less three wastes are produced, no pollution to the environment is caused, the total yield of the product is more than 94%, the purity is more than 96%, and the method is suitable for industrial production.
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Paragraph 0015; 0026; 0028; 0029; 0030; 0032; 0034
(2020/06/16)
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- Lanthanoid complexes supported by retro-Claisen condensation products of β-triketonates
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β-Triketonates have been recently used as chelating ligands for lanthanoid ions, presenting unique structures varying from polynuclear assemblies to polymers. In an effort to overcome low solubility of the complexes of tribenzoylmethane, four β-triketones with higher lipophilicity were synthesised. Complexation reactions were performed for each of these molecules using different alkaline bases in alcoholic media. X-ray diffraction studies suggested that the ligands were undergoing decomposition under the reaction conditions. This is proposed to be caused by in situ retro-Claisen condensation reactions, consistent with two examples that have been reported previously. The lability of the lanthanoid cations in the presence of a varying set of potential ligands gave rise to structures where one, two, or three of the molecules involved in the retro-Claisen condensation reaction were linked to the lanthanoid centres. These results, along with measurements of ligand decomposition in the presence of base alone, suggest the solvent used will modulate the impact of the retro-Claisen condensation in these complexes.
- Abad Galán, Laura,Sobolev, Alexandre N.,Zysman-Colman, Eli,Ogden, Mark I.,Massi, Massimiliano
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p. 17469 - 17478
(2019/01/03)
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- Synthesis, photo-sensitive and electrochemical properties of rod-like aromatic aldehyde with azo bridge
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Eight new rod-like liquid crystal molecules composed by a long rigid core of three six-member rings (cyclohexane ring or benzene ring), azo, ester and terminal aldehyde groups have been prepared. These rod-like liquid crystalline molecules were designed to construct new structures to further study photo-isomerization in their mesophases. All the compounds have been characterized based on their basic spectral data, differential scanning calorimeter (DSC) and hot stage polarizing optical microscope (HS-POM). The result showed that all the molecules, even those with the shortest terminal methyl group, have liquid crystalline properties. Their mesophases are nematic within the temperature ranges from 85 to 145°C. They exhibit photo-sensitivities not only in methanol solutions but also in a mesophase when exposed to UV light. The highest occupied orbital (HOMO) and the lowest unoccupied orbital (LUMO) and the differences between the frontier molecular orbitals (Eg) of these compounds were determined by cyclic voltammetry. The effect of even-odd carbon number of the terminal straight alkyl chain on the UV spectral data and the Eg were observed. The difference between the Eg of these compounds are in excellent agreement with the difference of their maximum absorption wavelength in UV spectra.
- Zheng, Minyan,Wei, Yongsheng,Geng, Wei
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p. 1071 - 1080
(2015/09/01)
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- Acid Chloride Synthesis by the Palladium-Catalyzed Chlorocarbonylation of Aryl Bromides
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We report a palladium-catalyzed method to synthesize acid chlorides by the chlorocarbonylation of aryl bromides. Mechanistic studies suggest the combination of sterically encumbered PtBu3 and CO coordination to palladium can rapidly equilibrate the oxidative addition/reductive elimination of carbon-halogen bonds. This provides a useful method to assemble highly reactive acid chlorides from stable and available reagents, and can be coupled with subsequent nucleophilic reactions to generate new classes of carbonylated products. The Good, the Bad and the Bulky! By employing a sterically encumbered phosphine ligand, tri-tert-butyl phosphine, under palladium catalysis inert aryl bromides are chlorocarbonylated to create reactive acid chlorides by reversible carbon-halogen bond reductive elimination. This general platform allows for an expanded scope of the Heck carbonylation reaction to include previously incompatible nucleophiles.
- Quesnel, Jeffrey S.,Kayser, Laure V.,Fabrikant, Alexander,Arndtsen, Bruce A.
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supporting information
p. 9550 - 9555
(2015/06/30)
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- Discovery and characterization of potent thiazoles versus methicillin- and vancomycin-resistant Staphylococcus aureus
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Methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) infections are growing global health concerns. Structure-activity relationships of phenylthiazoles as a new antimicrobial class have been addressed. We present 10 thiazole derivatives that exhibit strong activity against 18 clinical strains of MRSA and VRSA with acceptable PK profile. Three derivatives revealed an advantage over vancomycin by rapidly eliminating MRSA growth within 6 h, and no derivatives are toxic to HeLa cells at 11 μg/mL.
- Mohammad, Haroon,Mayhoub, Abdelrahman S.,Ghafoor, Adil,Soofi, Muhammad,Alajlouni, Ruba A.,Cushman, Mark,Seleem, Mohamed N.
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p. 1609 - 1615
(2014/03/21)
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- ANTIMICROBIAL SUBSTITUTED THIAZOLES AND METHODS OF USE
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Disclosed are compositions having activity against MRSA and/or VRSA, and methods of using the compositions to treat microbial infections.
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Paragraph 0049
(2014/05/08)
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- Synthesis and evaluation of some substituted heterocyclic fluconazole analogues as antifungal agents
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A new series of fluconazole analogues of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4- difluoro-phenyl)-3-4-(substituted-heterocyclic ring-1H-1,2,3- triazol-1-yl)-2-propanols (1-10) were designed, synthesized and evaluated as antifungal agents. Preliminary antifungal tests showed that most of the title compounds exhibited moderate activity with broad spectrum against eight human pathogenic fungi in vitro, compounds 1 and 6 had the best antifungal activity against Candida albicans with the value of MIC80 = 0.5 μg/mL respectively.
- Wang, Shudong,Zhang, Lei,Jin, Yongsheng,Tang, Jin Hao,Su, Hua,Yu, Shichong,Ren, Haixiang
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p. 2362 - 2364
(2014/06/09)
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- NOVEL MCH RECEPTOR ANTAGONISTS
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The present invention relates to a melanin concentrating hormone antagonist compound of formula (I); wherein Ar1, L1, R1, q, X, R2, R3, R4, and R5 are as defined, or a pharmaceutically acceptable salt, solvate, or enantiomer thereof useful in the treatment, prevention or amelioration of symptoms associated with obesity and related diseases.
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Page/Page column 60-61
(2008/06/13)
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- Liquid crystallinity of 2-fluorenyl 4-alkylbenzoates
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The liquid crystallinity values of 2-fluorenyl 4-alkyl (pentadecyl, n-, or s-butyl)-benzoates were compared with those of biphenyl homologues. Cyano group or hydrogen was used as the end group at the 7-position of 2-fluorenol moiety. Methoxy and hydroxy groups in addition to hydrogen were examined as a lateral substituent at the 2-position of 4-alkylbenzoic acid unit. 7-Cyano-2-fluorenyl 2-hydroxy-4-pentadecylbenzoate shows very similar properties to those of 4′-cyanobiphenyl-4-yl 2-hydroxy-4-pentadecylbenzoate.
- Yamamoto, Jun,Kimura, Takao,Takabayashi, Yutaka,Oba, Toru,Karikomi, Michinori,Minabe, Masahiro
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p. 523 - 528
(2007/10/03)
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- Preparation of new substituted bis(benzoyl) peroxides under aqueous conditions in the presence of stearyltrimethylammonium chloride
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A series of new substituted bis(benzoyl) peroxides has been synthesised from their corresponding acid chlorides in high yield. The reactions were carried out in aqueous sodium peroxide solution and butanone in the presence of 0.5% stearyltrimethylammonium chloride (STAC) at a temperature below 15°C. STAC improved the purity, and the fast addition improved the yield of the peroxides. Mass spectral analysis of substituted bis(benzoyl) peroxides using EI has been carried out for accurate mass determinations. Springer-Verlag 2003.
- Moorhoff, Cornelis M.,Braybrook, Carl
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p. 397 - 405
(2007/10/03)
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- SYNTHESIS AND LIQUID CRYSTAL PROPERTIES OF SUBSTITUTED 5-(ARYLCARBONYLOXY)-2-(p-CYANOPHENYL)PYRIMIDINES
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Liquid crystal p-substituted benzoates, biphenylcarboxylates, and benzoyloxybenzoates were obtained on the basis of 5-hydroxy-2-(p-cyanophenyl)pyrimidine.The development of nematogenicity by the esters due to the p-cyanophenyl grouping was noted, and the appearance of the smectic mesophase by the variation of the ring framework of the acid fragment of the molecule was investigated.
- Mikhaleva, M. A.,Igonina, G. A.,Savel'ev, V. A.
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p. 320 - 325
(2007/10/03)
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- Orientation of the benzophenone group at various depths in bilayers
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The hydrophobic core of biological membranes is primarily composed of fatty acyl chains of lipids and side chains of nonpolar amino acids belonging to membrane-spanning domains of transmembrane proteins. Electron transport across the 35-40-? membrane dielectric takes place via suitably oriented electron-transfer groups associated with transmembrane domains of membrane-bound proteins. We propose here that the design of lipids bearing electron-transport groups oriented at different depths can provide the necessary supramolecular assembly in the form of a monolayer or a bilayer to carry out electron transfer. The design of these modified lipids is crucial to the success of such a molecular device. We report here the design and synthesis of three benzophenone-based phospholipids capable of orienting the benzophenone group at different depths in a bilayer. The orientation of the benzophenone group was determined by photochemical cross-linking of these lipids with dimyristoylphosphatidylcholine in single bilayer vesicles followed by mass spectral analyses of the cross-linked products. The actual site of cross-linking on the myristoyl chain was determined, and it was observed that a range of carbon atoms are functionalized. The range of carbon atoms functionalized was found to be centered around the position expected from the transverse location of the benzophenone-based phospholipid in the bilayer. The data could be best interpreted in terms of zones of carbon atoms functionalized rather than any discreet site. This is in keeping with the current models of membranes which suggest the presence of a fluid gradient as one goes down the fatty acyl chain in the membrane. However, the range of carbon atoms functionalized was narrowed with probes reported here. The use of a hydrophobic tail attached to the benzophenone group assisted in directing the orientation of the photoactive group at different depths. Besides providing an effective design strategy for the orientation of electron-transfer groups at different depths in a bilayer, the high insertion yield and the depth-dependent labeling observed in artificial membranes suggest that the benzophenone-based phospholipids reported here could also prove useful for studying the structure of single and multiple spanning transmembrane proteins.
- Lala, Anil K.,Ravi Kumar
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p. 3982 - 3988
(2007/10/02)
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- Restudy of the Old Poly-2,5-di(benzoyloxy)styrene as a New Liquid Crystal Polymer
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The 40 year old polymer, poly-2,5-di(benzoyloxy)styrene, has been restudied from the view point of the "mesogen-jacketed liquid crystal polymer".This old polymer was synthesized in 1952 as a precursor of an electron exchange polymer and is now found to be thermotropically liquid crystalline, from which the characteristic banded texture of rigid and semi-rigid liquid crystal polymers may be obtained.The monomer of this polymer, 2,5-di(benzoyloxy)styrene, was then also not realized as liquid crystalline, is now found to be liquid crystalline forming too.This finding offers probably the first example of liquid crystal rigid rod-like molecules with lateral but without terminal substitutions.The synthesis and primary characterization of a series of the closely related polymers poly-2,5-bisstyrenes are also reported. - Keywords: mesogen jacketed liquid crystal polymers, rigid side chain liquid crystal polymers, liquid crystal monomers, liquid crystal polymers, 2,5-bisstyrene, 2,5-bisstyrene, 2,5-bisstyrene, 2,5-di(benzoyloxy)styrene, poly-2,5-di(benzoyloxy)styrene
- Zhou, Qi-Feng,Wan, Xinhua,Zhu, Xin-Long,Zhang, Fei,Feng, Xinde
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p. 107 - 118
(2007/10/02)
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- Potential Antiatherosclerotic Agents. 6. Hypocholesterolemic Trisubstituted Urea Analogues
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The discovery that a series of N,N-dialkyl-N'-arylureas were inhibitors of the ACAT enzyme has led to a structure-activity study involving the systematic modification of three sites of the urea backbone.This study culminated in the selection of N'-(2,4-dimethylphenyl)-N-benzyl-N-n-butylurea (115) for more extensive biological evaluation.ACAT inhibitors are seen as potentially beneficial agents against hypercholesterolemia and atherosclerosis.
- DeVries, Vern G.,Bloom, Jonathan D.,Dutia, Minu D.,Katocs, Andrew S.,Largis, Elwood E.
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p. 2318 - 2325
(2007/10/02)
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- LONG-ACTING CONTRACEPTIVE AGENTS: NORETHISTERONE ESTERS OF ARYLCARBOXYLIC ACIDS
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The synthesis of esters of norethisterone (17α-ethynyl-17β-hydroxyestr-4-en-3-one) with acids containing a benzene ring is described, two methods of esterification being compared in terms of yield and convenience.The activities of these esters as long-acting contraceptive agents have been evaluated.
- Wan, A. S. C.,Ngiam, T. L.,Leung, S. L.,Go, M. L.,Heng, P. W. S.,et al.
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p. 309 - 320
(2007/10/02)
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- Synthesis of Unbranched 4-Alkylbenzaldehydes
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The preparation of unbranched 4-alkylbenzaldehydes free of positional and branched-chain isomers by different methods is described.A one-step preparation of the aldehydes is reported which involves the direct hydrogenation of a Friedel-Craft's complex in the presence of Pd/C catalyst.
- Osman, Maged A.
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p. 2448 - 2449
(2007/10/02)
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- The Synthesis of Fluorine Containing Phenyl Benzoates and Their Properties as Liquid Crystals
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A new series of fluorine containing phenyl benzoates has been synthesized and the transition temperatures of these compounds have been determined.A series of 4-trifluoromethylphenyl 4-n-alkylbenzoates showed no liquid crystalline behaviour, but the 4-trifluoromethylphenyl 4-n-alkoxybenzoates series, with six carbons or more in alkoxy chain, was mesomorphic.The 4-cyanophenyl 4-perfluoroalkylbenzoates showed smectic liquid crystalline properties.
- Misaki, S.,Takamatsu, S.,Suefuji, M.,Mitote, T.,Matsumura, M.
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p. 123 - 132
(2007/10/02)
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- SYNTHESIS AND MESOMORPHIC PROPERTIES OF THE HOMOLOGOUS SERIES OF 4-ALKYL OR ALKOXY-4 prime -BROMO OR CYANOTOLANES.
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A homologous series of 4-alkyl or alkoxy-4 prime -bromo or cyanotolanes in which the alkyl group is C//4 yields C//1//0 and the alkoxy group is C//1 yields C//1//2, was prepared. Interphase transitions between solid, mesomorphic and isotropic phases were studied by hot stage microscopy and differential scanning calorimeter. The bromo compounds have a smectic polymorphism. Three pure products of cyano derivatives with the chains C//9H//1//9O, C//1//0H//2//1O amd C//1//0H//2//1 present an enantiotropic or monotropic reentrant nematic phase at atmospheric pressure. The reentrant phenomenon itself is discussed as well as the absence of correlation between T//N//A/T//N//I McMillan parameter and the heat of transition. A plot of the nematic isotropic transition temperatures against the number of carbon atoms in the alkoxy chain shows the usual odd even effect.
- Tinh,Pourrere,Destrade
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p. 125 - 139
(2007/10/02)
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