cas 2631-72-3, 2-Bromo-2',4'-dichloroacetophenone

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Discovery and high-throughput screening of heteroleptic iridium complexes for photoinduced hydrogen production
The catalytic process of photoinduced hydrogen generation via the reduction of water has been investigated. The use of parallel synthetic techniques has facilitated the synthesis of a 32 member library of heteroleptic iridium complexes that was screened, using high-throughput photophysical techniques, to identify six potential photosensitizers for use in catalytic photoinduced hydrogen production. A Pd/Ni thin film hydrogen selective sensor allowed for rapid quantification of hydrogen produced via illumination of aqueous systems of the photosensitizer, tris(2,2′-dipyridyl)dichlorocobalt ([Co(bpy) 3]Cl2), and triethanolamine (a sacrificial reductant) with ultra-bright light emitting diodes (LEDs). The use of an 8-well parallel photoreactor expedited the investigation of the hydrogen evolution process and facilitated mechanistic studies. All six compounds investigated produced considerably more hydrogen than commonly utilized photosensitizers and had relative quantum efficiencies of hydrogen production up to 37 times greater than that of Ru(bpy)32+.
Goldsmith, Jonas I.,Hudson, William R.,Lowry, Michael S.,Anderson, Timothy H.,Bernhard, Stefan
p. 7502 - 7510
(2005)
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Synthesis, single crystal X-ray, Hirshfeld surface analysis and characterization of novel 4-(2,4-dichlorophenyl)-N-(2,6-dichlorophenyl)-1,3-thiazol-2-amine
In the present study, the spectroscopic characterization of a novel thiazole scaffold was studied. The formation of title compound 4-(2,4-dichlorophenyl)-N-(2,6-dichlorophenyl)-1,3-thiazol-2-amine(6) was evidenced through the changes in FTIR, 1H NMR, LCMS Data. The X-ray diffraction studies revealed that compound (6) crystallized in monoclinic crystal system with P21/c Space group with Z = 4. The percentage of intermolecular contacts contributing to the Hirshfeld surface in thiazole crystal was resolved by Hirshfeld surface analyses with 2D fingerprint plots.
Gayathri,Dasappa, Jagadeesh Prasad,Bhavya,Chandra,Mahendra
p. 490 - 498
(2017)
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BuChE-IDO1 inhibitor as well as preparation method and application thereof
The invention relates to the field of medicines, and particularly discloses a BuChE-IDO1 inhibitor as well as a preparation method and application thereof. The 7-chlorine-3-substituted benzothiophene part of sertaconazole is chemically modified, the influence of the 7-chlorine-3-substituted benzothiophene part of sertaconazole on the in-vitro inhibitory activity of AChE, BuChE and IDO1 is explored, the target compound is further optimized, and the technical problems that an existing BuChE-IDO1 inhibitor is poor in pertinence and safety are solved. What is explored is that an appropriate substituent group introduced to a 2-benzothiazole ring can form additional interaction with surrounding amino acids and heme iron, so that the binding affinity of the analogue with BuChE and IDO1 is increased, and a new idea is broadened for more efficient and targeted treatment of advanced AD diseases.
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Paragraph 0031-0036

(2021/04/26)

Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies
In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
Zhou, You,Lu, Xin,Du, Chenxi,Liu, Yijun,Wang, Yifan,Hong, Kwon Ho,Chen, Yao,Sun, Haopeng
(2021/01/07)

Imidazole compound and preparation method and application thereof, organic solderable protective agent containing imidazole compound and surface treatment method
The invention relates to the technical field of precious metal surface treatment, and in particular, relates to the technical field of copper or copper alloy surface protection materials. The invention discloses a dichlorophenyl imidazole compound, an application of the dichlorophenyl imidazole compound serving as a film forming matter of an organic solderable protective agent, and an organic solderable protective agent. The invention also discloses an application of the compound in copper or copper alloy surface anti-oxidation treatment, and a surface treatment method of the copper or copperalloy, wherein the method comprises the following steps: infiltrating the surface of the copper or copper alloy with the organic weldable protective agent containing the compound, and drying to generate a coating layer on the surface.
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Paragraph 0152-0155; 0168-0171

(2020/05/05)

Antifungal water-soluble compound as well as preparation method and application thereof (by machine translation)
The invention provides an antifungal water-soluble compound, a preparation method thereof and application, of the compound as I shown in formula. The compound has good antifungal effect and water solubility, can be used for treating and preventing,configuration optical isomers of the optical isomer SRSS obtained by chiral synthesis. (by machine translation)
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Paragraph 0114-0116

(2020/06/02)

Novel thiazole–pyrazolone hybrids as potent ACE inhibitors and their cardioprotective effect on isoproterenol-induced myocardial infarction
A facile synthesis of a group of novel thiazole–pyrazolone hybrids and their investigation for angiotensin-converting enzyme (ACE) inhibition are reported in this study. These compounds were synthesized using a well-known approach, based on the condensation of ethyl acetoacetate with thiazolylhydrazines, and characterized by various spectroscopic and analytical techniques. The entire set of compounds displayed a moderate-to-excellent inhibitory activity against ACE. In particular, compound 4i was found to be the most potent ACE inhibitor and was further studied for cardioprotective effects against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Compound 4i improved the cardiac function and prevented cardiac injury induced by ISO in Sprague Dawley rats. The levels of oxidative stress and proinflammatory cytokines were also restored to near normal by 4i as compared with the ISO group. In the Western blot analysis, compound 4i prevented mitochondrial apoptosis after MI by downregulating the expression of cleaved caspase-3 and Bax, with the upregulation of Bcl-2, as compared with the ISO group.
You, Hongwen,Su, Xinyou,Su, Guoying
(2020/08/27)

Synthetic process of difenoconazole
The invention discloses a synthetic process of difenoconazole, comprising the steps of synthesizing 2,4-dichloroacetophenone through ionic liquid acylation using m-dichlorobenzene as a raw material; then synthesizing alpha-bromo-2,4-dichloroacetophenone through a green bromination method; subjecting the alpha-bromo-2,4-dichloroacetophenone and 1,2-propanediol to cyclization to generate a ketal compound that is 2-(2,4-dichlorophenyl)-2-bromomethyl-4-methyl-1,3-dioxolane; subjecting the ketal compound and 1,2,4-triazole potassium to condensation to generate 1-[[2-(2,4-dichlorophenyl)-4-methyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole; and finally subjecting the 1-[[2-(2,4-dichlorophenyl)-4-methyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole and parachlorophenol to etherification to obtain the difenoconazole. The process has advantages of easily available raw materials, a high reaction conversion ratio, few byproducts, capability of being friendly to production environment and a low cost.
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Paragraph 0013; 0014; 0018; 0019; 0024

(2019/07/16)

Synthesis technology for propiconazole
The invention discloses a synthesis technology for propiconazole. The synthesis technology comprises the following steps: 1) successively adding an organic solvent, 2,4-dichlorophenone, hydrogen peroxide and a catalyst into a reaction tank and dropwise adding liquid bromine; 2) keeping temperature at 40-45 DEG C for 1-8 hours and adding a reducing agent; 3) drying with magnesium sulfate and performing reduced pressure distillation; 4) cooling, separating and drying, thereby acquiring alpha-2,4-dichlorophenone; 5) adding methylbenzene, alpha-2,4-dichlorophenone, 1,2-pentanediol and p-toluene sulfonic acid into the reaction tank, heating till reflux reaction for 4-8 hours, and performing reduced pressure distillation, thereby acquiring 2-(2,4-dichlorophenyl)-2-bromine methyl-4-propyl-1,3-dioxolame; 6) adding dimethyl sulfoxide, catalyst, 1,2,4-triazole potassium and 2-(2,4-dichlorophenyl)-2-bromine methyl-4-propyl-1,3-dioxolame into the reaction tank, keeping temperature at 140 DEG C for5-10 hours, cooling, filtering, performing reduced pressure distillation, generating a salt with nitric acid, acidizing and neutralizing, performing reduced pressure distillation and purifying, thereby acquiring propiconazole. The synthesis technology disclosed by the invention is simple, environment-friendly and high in product purity.
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Paragraph 0018; 0020; 0022; 0024-0025

(2019/06/30)

Fragment splicing-based design, synthesis and safener activity of novel substituted phenyl oxazole derivatives
Fragment splicing is a primary strategy in the design and optimization of leading compound toward new skeleton with target bioactivity. Herein a series of novel substituted phenyl oxazole derivatives were designed via fragment analysis and coupling strategy that led to highly potent and bio-selective herbicide safener. The biological tests showed that most of the compounds could enhance the maize growth index, glutathione content and anti-reverse enzyme glutathione S-transferase activity in vivo. The molecular docking model exhibited that the novel compound could compete with chlorsulfuron binding to the herbicide target enzyme, which consequently attained the herbicide detoxification. Especially compound I-f displayed the best activities than commercial safener isoxadifen-ethyl and other compounds. The present work demonstrates that the synthesized compounds could be developed as potential candidates for the discovery of novel herbicide safeners in the future.
Fu, Ying,Zhang, Dong,Kang, Tao,Guo, You-Yuan,Chen, Wen-Geng,Gao, Shuang,Ye, Fei
p. 570 - 576
(2019/01/04)

Sterol 14α-Demethylase Structure-Based Design of VNI ((R)- N-(1-(2,4-Dichlorophenyl)-2-(1 H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)) Derivatives to Target Fungal Infections: Synthesis, Biological Evaluation, and Crystallographic Analysis
Because of the increase in the number of immunocompromised patients, the incidence of invasive fungal infections is growing, but the treatment efficiency remains unacceptably low. The most potent clinical systemic antifungals (azoles) are the derivatives of two scaffolds: ketoconazole and fluconazole. Being the safest antifungal drugs, they still have shortcomings, mainly because of pharmacokinetics and resistance. Here, we report the successful use of the target fungal enzyme, sterol 14α-demethylase (CYP51), for structure-based design of novel antifungal drug candidates by minor modifications of VNI [(R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)], an inhibitor of protozoan CYP51 that cures Chagas disease. The synthesis of fungi-oriented VNI derivatives, analysis of their potencies to inhibit CYP51s from two major fungal pathogens (Aspergillus fumigatus and Candida albicans), microsomal stability, effects in fungal cells, and structural characterization of A. fumigatus CYP51 in complexes with the most potent compound are described, offering a new antifungal drug scaffold and outlining directions for its further optimization.
Friggeri, Laura,Hargrove, Tatiana Y.,Wawrzak, Zdzislaw,Blobaum, Anna L.,Rachakonda, Girish,Lindsley, Craig W.,Villalta, Fernando,Nes, W. David,Botta, Maurizio,Guengerich, F. Peter,Lepesheva, Galina I.
p. 5679 - 5691
(2018/06/22)

Investigation of multi-target-directed ligands (MTDLs) with butyrylcholinesterase (BuChE) and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition: The design, synthesis of miconazole analogues targeting Alzheimer's disease
In our endeavor towards the development of potent multi-target ligands for the treatment of Alzheimer's disease, miconazole was identified to show BuChE-IDO1 dual-target inhibitory effects. Morris water maze test indicated that miconazole obviously ameliorated the cognitive function impaired by scopolamine. Furthermore, it showed good safety in primary hepatotoxicity evaluation. Based on these results, we designed, synthesized, and evaluated a series of miconazole derivatives as BuChE-IDO1 dual-target inhibitors. Out of the 12 compounds, 5i and 5j exhibited the best potency in enzymatic evaluation, thus were selected for subsequent behavioral study, in which the two compounds exerted much improved effect than tacrine. Meanwhile, 5i and 5j displayed no apparent hepatotoxicity. The results suggest that miconazole analogue offers an attractive starting point for further development of new BuChE-IDO1 dual-target inhibitors against Alzheimer's disease.
Lu, Xin,He, Si-yu,Li, Qi,Yang, Hongyu,Jiang, Xueyang,Lin, Hongzhi,Chen, Yao,Qu, Wei,Feng, Feng,Bian, Yaoyao,Zhou, You,Sun, Haopeng
p. 1665 - 1674
(2018/02/23)

Method for synthesizing azaconazole through 4-amino-4H-1,2,4-triazole alkylation
The invention discloses a method for synthesizing azaconazole through 4-amino-4H-1,2,4-triazole alkylation. The method comprises step 1, preparing a raw material which is shown in a following image; step 2, synthesizing 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazole-1-yl) ethanone; step 3, synthesizing azaconazole. The method disclosed by the invention has the advantages that development of a novel azaconazole bactericide successfully fills the blank in China, synthesis researches of similar derivatives based on the azaconazole bactericide will be in the ascendant, and successful development andindustrial implementation of varieties of novel bactericides have a far-reaching influence on national economy development. The method disclosed by the invention is an azaconazole synthesizing method.
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Paragraph 0035

(2018/11/03)

Synthesis method of azaconazole intermediate
The invention discloses a synthesis method of an azaconazole intermediate. The synthesis method mainly comprises a synthesis method of 2,4-dichloroacetophenone, a synthesis method of 2-bromo-1-(2,4-dichlorophenyl) ethyl ketone, and a synthesis method of ketal. The preparation method has the advantages that the development of the novel azaconazole bactericide fills up a domestic blank in the field,similar derivative synthesis research based on the synthesis method is in the ascendant, and successful development and industrial implementation of various novel bactericides can be realized. The invention provides a novel azaconazole synthesis method.
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Paragraph 0037

(2019/01/04)

Novel arylimino thiazole compound, preparation method and uses thereof
The present invention relates to a compound with antibacterial synergy activity, a preparation and uses thereof, particularly to a novel arylimino thiazole compound, a preparation method and uses thereof, and specifically discloses a class of compounds represented by a formula (I) or optical isomers, cis-trans isomers or pharmaceutically acceptable salts thereof, a preparation method and uses thereof. The invention further discloses a pharmaceutical composition containing the compound. The compound of the present invention can effectively enhance the antibacterial activity of antibiotics, andcan be used for treating antibiotic-resistant bacteria. The formula (I) is defined in the specification.
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Paragraph 0226; 0229; 0230; 0231

(2018/03/28)

Antibacterial synergist, preparation method and uses thereof
The present invention relates to an antibacterial synergist, a preparation method and uses thereof, and specifically discloses a compound represented by a formula (I) and having antibacterial synergyactivity, or an optical isomer, a cis-trans isomer or a pharmaceutically acceptable salt thereof, and a preparation method thereof. The present invention further discloses a medical composition containing the compound, and uses thereof. According to the present invention, the compound can effectively enhance the antibacterial activity of polymyxin B against Acinetobacter baumannii and Klebsiella pneumoniae, and can be used for the antibacterial treatment of pathogenic bacteria insensitive to polymyxin or having low bacterial inhibition activity. The formula (I) is defined in the specification.
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Paragraph 0332; 0333; 0334; 0335

(2018/03/28)

Novel Tetrazole-Containing Analogues of Itraconazole as Potent Antiangiogenic Agents with Reduced Cytochrome P450 3A4 Inhibition
Itraconazole has been found to possess potent antiangiogenic activity, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4). In an effort to eliminate the CYP3A4 inhibition while retaining its antiangiogenic activity, we designed and synthesized a series of derivatives in which the 1,2,4-triazole ring is replaced with various azoles and nonazoles. Among these analogues, 15n with tetrazole in place of 1,2,4-triazole exhibited optimal inhibition of human umbilical vein endothelial cell proliferation with an IC50 of 73 nM without a significant effect on CYP3A4 (EC50 > 20 μM). Similar to itraconazole, 15n induced Niemann-Pick C phenotype (NPC phenotype) and blocked AMPK/mechanistic target of rapamycin signaling. These results suggest that 15n is a promising angiogenesis inhibitor that can be used in combination with most other known anticancer drugs.
Li, Yingjun,Pasunooti, Kalyan Kumar,Li, Ruo-Jing,Liu, Wukun,Head, Sarah A.,Shi, Wei Q.,Liu, Jun O.
supporting information
p. 11158 - 11168
(2019/01/08)

Preparation method of ketoconazole
The invention belongs to the technical field of medicine synthesis and in particular relates to a preparation method of ketoconazole. The preparation method of the ketoconazole, provided by the invention, comprises the following step: S101: enabling a compound shown as a formula I and a compound shown as a formula II to be mixed for reaction in an acidic medium to obtain the ketoconazole. According to the preparation method of the ketoconazole, the steric hindrance of the compound shown as the formula I and the compound shown as the formula II is great, so that the cis-trans selectivity of 1,3-dioxolame formed by reaction of the compound shown as the formula I and the compound shown as the formula II is remarkably improved, and furthermore, a benzoyl removing step is omitted; finally, theproduction period of the ketoconazole is shortened and the cost is reduced; meanwhile, the utilization of dangerous substances including bromine liquid and the like is reduced; the technical defects in the prior art that steps for synthesizing the ketoconazole is more and the yield and the purity are low are overcome.
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Paragraph 0037; 0047; 0049

(2018/04/03)

Synthesis of Novel 4-(Dimethylaminoalkyl)piperazine-1-carbodithioa t e Derivatives as Cholinesterase Inhibitors
Background: Carbamate compounds have attracted a great deal of interest in medicinal chemistry due to their inhibition potential against cholinesterase enzymes. Method: Hence, this study was undertaken to synthesize new piperazine derivatives including dithiocarbamate moiety, which is the bioisoster of carbamate. Twenty eight 4-(dimethylaminoalkyl) piperazine-1-carbodithioate derivatives (3a-3n, 4a-4n) were synthesized. Chemical structures of these compounds were confirmed by spectral data. Ellman's assay was applied in order to investigate inhibitory potency of the compounds against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzymes. Results and Conclusion: It was determined that some of the compounds have remarkable activity on AChE. ADME (Absorption, distribution, metabolism, elimination) predictions were theoretically performed for all compounds in the series. Enzyme kinetics and molecular docking studies were carried out for the most active compound (3n) and nature of inhibition and interactions between enzyme and ligand were described.
?evik, Ulviye Acar,Levent, Serkan,Saglik, Begüm Nurpelin,?zkay, Yusuf,Kaplancikli, Zafer Asim
p. 528 - 539
(2017/06/01)

Citric Acid-catalyzed Synthesis of 2,4-Disubstituted Thiazoles from Ketones via C–Br, C–S, and C–N Bond Formations in One Pot: A Green Approach
An improved and greener protocol has been developed for the synthesis of 2,4-disubstituted thiazoles via C–Br, C–S, and, C–N bond formations in a single step from readily available ketones, N-bromosuccinimide (NBS), and thiourea catalyzed by citric acid in a mixture of ethanol and water (3:1) under reflux conditions. This method has the advantages of freedom from the isolation of lachrymatory α-bromoketones, ease of carrying out, cleaner reaction profile, broad substrate scope, freedom from chromatographic purification, and suitability for large-scale synthesis.
Gundala, Trivikram Reddy,Godugu, Kumar,Nallagondu, Chinna Gangi Reddy
p. 1408 - 1416
(2017/10/23)

Strategic synthesis and in vitro antimicrobial evaluation of novel difluoromethylated 1-(1, 3-diphenyl-1H-pyrazol-4-yl)-3, 3-difluoro-1, 3-dihydro-indol-2-ones
A strategic synthesis of 1-(1,3-diphenyl-1H-pyrazol-4-yl)-3,3-difluoro-1,3-dihydro-indol-2-ones has been achieved by the reaction of indole-2,3-dione (isatin) and substituted bromoacetyl benzene followed by cyclization reaction and evaluated for in vitro antibacterial and antifungal activities. Direct fluorination using diethylaminosulfur trifluoride as a nucleophilic fluorinating reagent was carried out in the present paper. Undoubtedly this methodology gives a facile and straightforward pathway to construct 1-(1,3-diphenyl-1H-pyrazol-4-yl)-3,3-difluoro-1,3-dihydro-indol-2-ones in good yields. The structure of new fluorinated 1-(1,3-diphenyl-1H-pyrazol-4-yl)-3,3-difluoro-1,3-dihydro-indol-2-ones was characterized based on 1H, 13C, and 19F nuclear magnetic resonance spectroscopy and mass spectrometry data. Structure of target compound was confirmed by Nuclear Overhauser Effect Spectroscopy spectra. Some of the synthesized compounds showed good antimicrobial activities against bacteria and fungi.
Chundawat, Tejpal Singh,Kumari, Poonam,Sharma, Nutan,Bhagat, Sunita
p. 2335 - 2348
(2016/10/25)

Synthesis and antimicrobial activity evaluation of new dithiocarbamate derivatives bearing thiazole/benzothiazole rings
The synthesis of 2-(substituted phenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A1-A24) derivatives and 2-(4-substituted thiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B1-B14) derivatives was undertaken starting from the potassium salt of 4-(2-pyrimidinyl)piperazine dithiocarbamate. The structures of the obtained compounds were elucidated by1H NMR,13C NMR, MS spectral data, and elemental analysis. The antimicrobial activity of the thirty eight newly synthesized compounds were tested against 12 microorganism strains using the microdilution technique. Compounds 2-(4-ethoxycarbonylthiazol-2-ylamino)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (B12), 2-(3-fluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A18) and 2-(3,4-difluorophenyl)-2-oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithiodate (A21) were determined to possess high antimicrobial activity.
Yurtta?, Leyla,?zkay, Yusuf,Duran, Murat,Turan-Zitouni, Gülhan,?zdemir, Ahmet,Cantürk, Zerrin,Kü?üko?lu, Kaan,Kaplanc?kl?, Zafer As?m
p. 1166 - 1173
(2016/07/27)

Synthesis and antimicrobial evaluation of aminoguanidine and 3-amino-1,2,4-triazole derivatives as potential antibacterial agents
A series of aminoguanidine derivatives bearing a 1,3,4-oxadiazole or piperazine moiety has been synthesized and fully characterized together with a series of 3-amino-1,2,4-triazole derivatives, and the resulting compounds were evaluated for their antibacterial activity. Most of these compounds showed broad-spectrum antibacterial activities against both Gram-positive and Gramnegative bacteria with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values in the range of 1-64 μg/mL, including multidrug-resistant clinical isolates and a fungus. Notably, compounds 19e and 19f exhibited higher levels of activity than gatifloxacin and moxifloxacin against several methicillin-resistant Staphylococcus aureus (3167 and 3506) and quinolone-resistant S. aureus (3505 and 3519) strains with MIC and MBC values in the range of 1-2 μg/mL. These two compounds also displayed significant antifungal activity against Candida albicans 7535 with MIC value of 1 μg/mL, which were equivalent to MIC value of standard drug fluconazole. These results therefore indicate that aminoguanidine derivatives that do not contain a piperazine moiety are interesting scaffolds for the development of novel antibacterial agents.
Zhang, Tian-Yi,Li, Chao,Li, Ya-Ru,Li, Xiao-Zhen,Sun, Liang-Peng,Zheng, Chang-Ji,Piao, Hu-Ri
p. 1063 - 1075
(2016/11/25)

Synthesis and characterization of novel oxime derivatives
Background: The synthesis of effective drugs are very important for the scientist. The various biological effects of the thiazole, oxime and ether functional groups are well known properties by the drug developers. So we have synthesised new molecules which contains three of them on the same molecules. Methods: The acetophenone derivatives have been used for synthesis new oximes. The synthetic pathway includes mainly four steps. s1. α-Bromination of acetophenone derivatives, s2. Synthesis of thiazole ring using brominated acetophenones, s3. Synthesis of ethers using synthesised thiazole, s4. Synthesis of oximes. Results: The synthesised molecules characterised using IR,1H-NMR, 13C-NMR and elementel analysis methods. Conclusion: The new oximes which include thiazole and ether groups have been synthesised using acetophenone derivatives.
Arslan, Taner,Keskin, Serhat,Demirayak, Seref
p. 672 - 677
(2017/01/13)

NOVEL FUNCTIONALIZED 5-(PHENOXYMETHYL)-1,3-DIOXANE ANALOGS EXHIBITNG CYTOCHROME P450 INHIBITION
Pharmaceutical compositions described in this document comprise 5-(phenoxymethyl)-1,3-dioxane analogs having a disease-modifying action in the treatment of diseases associated with the production of cortisol that include metabolic syndrome, obesity, headache, depression, hypertension, diabetes mellitus, Cushing's Syndrome, pseudo-Cushing syndrome, cognitive impairment, dementia, heart failure, renal failure, psoriasis, glaucoma, cardiovascular disease, cancer, stroke, incidentalomas, or any diseases involving the overproduction of cortisol.
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Paragraph 0191; 0192

(2015/04/15)

Design, Synthesis and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel DPP-4 Inhibitors
A new series of DPP-4 inhibitors with imidazo[1,2-a]pyridine scaffold were designed by exploiting scaffold hopping strategy and docking study. Based on docking binding model, structural modifications of 2-benzene ring and pyridine moieties of compound 5a led to the identification of compound 5d with 2, 4-dichlorophenyl group at the 2-position as a potent (IC50 = 0.13 μm), selective (DPP-8/DPP-4 = 215 and DPP-9/DPP-4 = 192) and in vivo efficacious DPP-4 inhibitor. Further, molecular docking revealed that compound 5d could retain key binding features of DPP-4 with the pyridine moiety of imidazo[1,2-a]pyridine ring providing an additional π-π interaction with Phe357 of DPP-4. Compound 5d might be a promising lead for further development of novel DPP-4 inhibitor treating T2DM.
Li, Qing,Zhou, Muxing,Han, Li,Cao, Qing,Wang, Xinning,Zhao, Leilei,Zhou, Jinpei,Zhang, Huibin
p. 849 - 856
(2015/10/06)

Click chemistry inspired synthesis of piperazine-triazole derivatives and evaluation of their antimicrobial activities
A series of novel piperazine-1,2,3-triazole derivatives, which entailed the bioisosteric replacement of the imidazole moiety and hybridization of two drug scaffolds was prepared by employing the regioselective copper (I)-catalysed azide-alkyne 1,3-dipolar cycloaddition reaction. The synthesized compounds were evaluated for antibacterial activities against Gram-negative (E. Coli and P. Putida), Gram-positive S. Aureus bacteria and fungicidal activities against F. oxysporum, F. gramillarium and F. monalliforme fungi. Compound 7ac′ exhibited moderate but promising antibacterial activity against Gram-negative bacteria and fungicidal activity against F. oxysporum and F. gramillarium.
Khedar, Poonam,Pericherla, Kasiviswanadharaju,Singh, Rajnish Prakash,Jha, Prabhat Nath,Kumar, Anil
p. 3117 - 3126
(2016/02/10)

Rational design and synthesis of novel 2-(substituted-2H-chromen-3-yl)-5-aryl-1H-imidazole derivatives as an anti-angiogenesis and anti-cancer agent
Based on earlier proven pharmacophore analogues of cancer a novel 2-(substituted-2H-chromen-3-yl)-5-aryl-1H-imidazoles (13-16) were rationally designed and synthesized by the reaction of chromene-3-carboxylic acids (10a-d) with substituted acyl bromides in the presence of TEA followed by refluxing with NH4OAc in toluene. Compounds 13-16 were screened in vitro for the inhibition of KRAS/Wnt and their anti-angiogenesis properties. Compound 16f has been identified as a potent anti-angiogenesis molecule, which can be considered as a new lead structure. The molecular docking analysis displayed the higher binding affinity of 16f with KRAS, Wnt and VEGF.
Gudipudi, Gopinath,Sagurthi, Someswar R.,Perugu, Shyam,Achaiah,Krupadanam, G. L. David
p. 56489 - 56501
(2015/02/05)

Flexible routes to thiophenes
Three convergent routes to thiophenes are described, hinging on the radical addition of α-xanthyl ketones to ethyl vinyl sulfide or to vinyl pivalate. The latter route ultimately proved to be the most versatile and efficient (61-94%).
Jullien, Helene,Quiclet-Sire, Beatrice,Tetart, Thomas,Zard, Samir Z.
supporting information
p. 302 - 305
(2014/01/23)

De novo design of non-coordinating indolones as potential inhibitors for lanosterol 14-α-demethylase (CYP51)
The development of antifungal drugs that inhibit lanosterol 14-α-demethylase (CYP51) via non-covalent ligand interactions is a strategy that is gaining importance. A series of novel tetraindol-4-one derivatives with 1- and 2-(2,4-substituted phenyl) side chains were designed and synthesized based on the structure of CYP51 and fluconazole. The antifungal activities of these derivatives against eight human pathogenic filamentous fungi and yeast strains were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds 8a-g displayed activity against Candida tropicalis, Candida guilliermondii and Candida parapsilosis with a minimum inhibitory concentration (MIC) value until 8 μg mL-1, on the other hand compounds 7a-g showed activity against Aspergillus fumigatus with a MIC value of 31.25 μg mL-1. A molecular modeling study of the binding interactions between compounds 6, 7d, 8g and the active site of MtCYP51 was conducted based on the computational docking results.
Gonzalez-Chavez, Rodolfo,Martinez, Roberto,Torre-Bouscoulet, Maria Eugenia,Gallo, Marco,Gonzalez-Chavez, Marco Martin
p. 16 - 24
(2014/01/23)

Synthesis and evaluation of non-dimeric HCV NS5A inhibitors
Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a showed picomolar range activity along with an excellent selectivity index (SI > 90,000).
Amblard, Franck,Zhang, Hongwang,Zhou, Longhu,Shi, Junxing,Bobeck, Drew R.,Nettles, James H.,Chavre, Satish,McBrayer, Tamara R.,Tharnish, Philip,Whitaker, Tony,Coats, Steven J.,Schinazi, Raymond F.
p. 2031 - 2034
(2013/05/09)

Synthesis and cytotoxicity of novel (thiazol-2-yl)hydrazine derivatives as promising anti-Candida agents
Thirty-eight new (4-(4-substituted-phenyl/2,4-disubstituted-phenyl)- thiazol-2-yl)hydrazine derivatives were synthesized in good yield and assayed for their in vitro anti-Candida activity, compared to topical and systemic antifungal drugs, against twenty-two clinical isolates of Candida spp. The concurrent presence of aliphatic chains or cycloaliphatic rings at N1-hydrazine and a 4-methyl/4-methoxyphenyl at C4 position of the thiazole nucleus exhibited an interesting anti-Candida inhibitory activity. Moreover, some of the most active compounds showed synergistic antifungal effects and lower cell toxicity when combined with clotrimazole.
Carradori, Simone,Secci, Daniela,Bolasco, Adriana,Rivanera, Daniela,Mari, Emanuela,Zicari, Alessandra,Lotti, Lavinia Vittoria,Bizzarri, Bruna
p. 102 - 111
(2013/10/01)

Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes
Present studies have shown that the lipid carrier has a significant role in several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives were synthesized and investigated for their inhibitory effects on the production of LPS-stimulated TNF-α. Among them, 12b exhibited an excellent inhibitory efficiency compared to BMS309403 (95% vs. 85%) at the concentration of 10 μM and a binding affinity for ap2 with the apparent Ki values 33 nM. Oral administration of 12b at a dosage of 50 mg/kg effectively reduced the levels of plasma blood glucose, triglycerides, insulin, total cholesterol and alanine aminotransferase in high-fat/diet-induced obesity model. The results highlighted that 12b was a potent anti-diabetic agent.
Xu, Qinyuan,Huang, Li,Liu, Juan,Ma, Liang,Chen, Tao,Chen, Jinying,Peng, Fei,Cao, Dong,Yang, Zhuang,Qiu, Neng,Qiu, Jingxiang,Wang, Guangcheng,Liang, Xiaolin,Peng, Aihua,Xiang, Mingli,Wei, Yuquan,Chen, Lijuan
experimental part
p. 70 - 81
(2012/07/30)

Synthesis and bioactivity evaluation of rhodanine derivatives as potential anti-bacterial agents
Five series of (Z)-5-(4-(2-oxo-2-phenylethoxy)benzylidene)-2- thioxothiazolidin-4-one derivatives (I-V) were synthesized, characterized, and evaluated for their anti-bacterial activity. Most of the synthesized compounds showed potent inhibition against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with MIC values in the range of 1-32 μg/mL. Compounds IIIi, Vb and Vc presented the most potent activity, showing four-fold more potency than norfloxacin (MIC = 8 μg/mL and 4 μg/mL) and 64-fold more activity than oxacillin (MIC > 64 μg/mL) against MRSA CCARM 3167 and 3506 strains with MIC values of 1 μg/mL, and 64-fold more potency than norfloxacin (MIC > 64 μg/mL) and comparable activity to oxacillin (MIC = 1 μg/mL) against the QRSA CCARM 3505 and 3519 strains. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL.
Song, Ming-Xia,Zheng, Chang-Ji,Deng, Xian-Qing,Wang, Qing,Hou, Shao-Pu,Liu, Ting-Ting,Xing, Xiao-Lan,Piao, Hu-Ri
experimental part
p. 403 - 412
(2012/10/08)

Click chemistry inspired structural modification of azole antifungal agents to synthesize novel 'drug like' molecules
A new class of 'drug like' 1,4-disubstituted-1,2,3-triazoles is synthesized using one-pot reaction of sodium azide, α-bromo ketones, and alkynes in PEG-400/water (1:1, v/v) under the click chemistry reaction condition followed by reduction of keto group and alkylation. The method is simple, efficient and gives good yield of novel 1,2,3-triazole derivatives.
Pericherla, Kasiviswanadharaju,Khedar, Poonam,Khungar, Bharti,Kumar, Anil
supporting information
p. 6761 - 6764
(2013/01/15)

Structure-activity relationships of 2,4-diphenyl-1H-imidazole analogs as CB2 receptor agonists for the treatment of chronic pain
A series of 2,4-diphenyl-1H-imidazole analogs have been synthesized and displayed potent human CB2 agonist activity. Many of these analogs showed high functional selectivity over human CB1 receptors. The syntheses, structure-activity relationships, and selected pharmacokinetic data of these analogs are described.
Yang, Shu-Wei,Smotryski, Jennifer,Matasi, Julius,Ho, Ginny,Tulshian, Deen,Greenlee, William J.,Brusa, Rossella,Beltramo, Massimiliano,Cox, Kathleen
scheme or table
p. 182 - 185
(2011/02/27)

Synthesis and biological evaluation of substituted 4-arylthiazol-2-amino derivatives as potent growth inhibitors of replicating Mycobacterium tuberculosis H37RV
In search of potential therapeutics for tuberculosis, we describe herein synthesis and biological evaluation of some substituted 4-arylthiazol-2-amino derivatives as modified analogues of the antiprotozoal drug Nitazoxanide (NTZ), which has recently been reported as potent inhibitor of Mtb H37Rv (Mtb MIC = 52.12 μM) with an excellent ability to evade resistance. Among the synthesized derivatives, the two compounds 7a (MIC = 15.28 μM) and 7c (MIC = 17.03 μM) have exhibited about three times better Mtb growth inhibitory activity over NTZ and are free from any cytotoxicity (Vero CC50 of 244 and 300 μM respectively). These two compounds represent promising leads for further optimization.
Roy, Kuldeep K.,Singh, Supriya,Sharma, Sandeep K.,Srivastava, Ranjana,Chaturvedi, Vinita,Saxena, Anil K.
supporting information; experimental part
p. 5589 - 5593
(2011/10/12)

α-Halogenation of carbonyl compounds: Halotrimethylsilane-nitrate salt couple as an efficient halogenating reagent system
A mixture of chloro/bromotrimethylsilane and nitrate salt is found to be an effective reagent system for the α-chlorination/bromination of carbonyl compounds. The reaction occurs under mild conditions yielding the products in moderate to good yields.
Prakash, G.K. Sxurya,Ismail, Rehana,Garcia, Jessica,Panja, Chiradeep,Rasul, Golam,Mathew, Thomas,Olah, George A.
experimental part
p. 1217 - 1221
(2011/03/22)

Mild and efficient method for-thiocyanation of ketones and-dicarbonyl compounds using bromodimethylsulfonium bromide-ammonium thiocyanate
An efficient and convenient method for-thiocyanation of ketones and-dicarbonyl compounds has been developed using a reagent combination of bromodimethylsulfonium bromide (BDMS) and ammonium thiocyanate in acetonitrile. The developed method is mild and gave good yield of the products at room temperature.
Bhalerao, Dinesh S.,Akamanchi, Krishnacharya G.
experimental part
p. 799 - 807
(2010/05/17)

Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors
The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds.
Chimenti, Franco,Secci, Daniela,Bolasco, Adriana,Chimenti, Paola,Granese, Arianna,Carradori, Simone,MacCioni, Elias,Cardia, M. Cristina,Yanez, Matilde,Orallo, Francisco,Alcaro, Stefano,Ortuso, Francesco,Cirilli, Roberto,Ferretti, Rosella,Distinto, Simona,Kirchmair, Johannes,Langer, Thierry
experimental part
p. 5063 - 5070
(2010/09/08)

Synthesis of optically active β-amino alcohols by asymmetric transfer hydrogenation of α-amino ketones
A number of optically active amino alcohols were synthesized by direct asymmetric transfer hydrogenation of the corresponding amino ketones with good-to-high enantiomeric excesses (up to 95%) and excellent yields (up to 93%). When the range of substrates was broadened to include α-sulfonamido ketones or α-keto sulfones, the corresponding products were obtained with 100% enantiomeric excesses. The absolute configuration of (1R)-2-[(4- chlorophenyl) amino]-1-(4-methoxyphenyl) ethanol was confirmed by X-ray crystal structure analysis. Georg Thieme Verlag Stuttgart.
Xu, Zhou,Zhu, Songlei,Liu, Yongmin,He, Ling,Geng, Zhicong,Zhang, Yawen
scheme or table
p. 811 - 817
(2010/10/01)

One-pot synthesis of 2-aminothiazoles in PEG-400
A facile one-pot synthesis of 2-aminothiazoles has been carried in PEG-400 as a greener medium at room temperature. This method avoids the use of lachrymatric α-bromoketones as well as the volatile, toxic organic solvents.
Jawale, Dhanaji V.,Lingampalle, Dinesh L.,Pratap, Umesh R.,Mane, Ramrao A.
experimental part
p. 412 - 416
(2010/12/24)

Synthesis, structure, and biological activity of novel 1H-1,2,4-triazol-1- yl-thiazole derivatives
2-Amino-4-aryl-5-(1H-1,2,4-triazol-1-yl)thiazole derivatives were synthesized from the reaction of α-bromo substituted acetophenone and thiourea. The structures were confirmed by elemental analysis, 1H NMR and single crystal X-ray diffraction analysis. Biological evaluation showed that some of them possess antifungal and plant growth regulatory activities. Copyright Taylor & Francis Group, LLC.
Ling, Shao,Xin, Zhou,Qing, Zhang,Jian-Bing, Liu,Zhong, Jin,Jian-Xin, Fang
p. 199 - 207
(2007/10/03)

Synthesis and QSAR studies of novel triazole compounds containing thioamide as potential antifungal agents
Eighteen novel triazole compounds containing thioamide were designed and synthesized. Their structures were confirmed by elemental analysis, 1H NMR, IR, and MS. The title compounds exhibited certain antifungal activity. And the geometry structures of the title compounds were optimized by means of the density functional theory (DFT) method at B3LYP/6-31G* level. The quantitative structure-activity relationship (QSAR) of the title compounds was systematically investigated. A correlative equation between FA and DELH, V was well established by using the multiple linear regression (MLR).
Wei, Qing-Li,Zhang, Shu-Sheng,Gao, Jun,Li, Wei-hua,Xu, Liang-Zhong,Yu, Zhi-Gang
p. 7146 - 7153
(2007/10/03)

Substituted pyrimidines
Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.
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(2010/02/14)

Benzofuranylsulfonates
The invention relates to benzofuranylsulfonates of the general formula (I), their preparation and their use for the treatment of inflammation.
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(2008/06/13)

3-O-Substituted benzyl pyridazinone derivatives as COX inhibitors
New 3-O-substituted benzyl pyridazinone compounds have been synthesised and evaluated for their cyclooxygenase inhibitory activity and COX-2 selectivity. Among the compounds synthesised, three compounds (11b-11d) have shown in vitro COX-2 selectivity. These compounds have been evaluated for their in vivo potential using carrageenan-induced rat paw edema assay. One compound (11b) showed 32% anti-inflammatory activity at 30 mg kg-1 dose.
Chintakunta, Vamsee Krishna,Akella, Venkateswarlu,Vedula, Manohar Sharma,Mamnoor, Prem Kumar,Mishra, Parimal,Casturi, Seshagiri Rao,Vangoori, Akhila,Rajagopalan, Ramanujam
p. 339 - 347
(2007/10/03)

Antifungal amine derivatives and processing for producing the same
Novel amine derivatives having an excellent antimycotic effect represented by general formula (1) below and salts thereof are provided. [in the formula (1, R1represents a C1-5alkyl group which may be halogenated, R2represents 4-(1,1-dimethylalkyl)benzyl group, 4-(1-methyl-phenylethyl)benzyl group, 1-or 2-naphthylmethyl group, or a hydrocarbon group having 3,3-dimethyl-1-butynyl group or a phenyl group at its terminal and 1 to 3 double bonds; R3represents oxygen atom or a methylene group which may be substituted by a C1-4alkyl group; and R4represents 1-or 2 naphthyl group or a phenyl group which may be substituted.
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(2008/06/13)

Aromatic ethers of 1-aryl 2-(1H-azolyl)ethanol: study of antifungal activity
Aromatic ethers related to antifungal azole miconazole were synthesized and tested against various strains of Candida.We found that activity is related to the nature of the aromatic ring and the position of substituents on this ring.Activity is more strongly dependent on the substituent in the 2-position of the ethyl chain on the aromatic group linked through the oxygen.Triazoles were always less potent than the corresponding imidazole analogues. - Keywords: imidazole; 1,2,4-triazole; antifungal activity; yeast; structure-activity relationship
Wahbi, Y.,Caujolle, R.,Tournaire, C.,Payard, M.,Linas, M. D.,Seguela, J. P.
p. 955 - 962
(2007/10/03)

Synthesis and antifungal activity evaluation of 3-hydroxyimidazo[1,2-a]pyridine and 3-hydroxyimidazo[1,2-a]pyrimidine derivatives
A series of 16 imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine derivatives was synthesized and tested on several species for 'in vitro' fungicide activity.
Rival,Taudou,Ecalle
p. 857 - 869
(2007/10/02)