- PREPARATION OF PYRAZOLO[3,4-B]PYRIDINES AS ANTIMALARIALS
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The present invention relates to pyrazolo[3,4-b]pyridine compounds. The present invention further relates to methods for inhibiting Plasmodium comprising contacting Plasmodium with pyrazolo[3,4-b]pyridine compounds described herein. Also described herein are methods of treating malaria comprising administering pyrazolo[3,4-b]pyridine compounds to a subject in need thereof.
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Paragraph 0204
(2021/04/10)
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- Nucleus-independent chemical shift (NICS) as a criterion for the design of new antifungal benzofuranones
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The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p –1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 μg·mL–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.
- González-Chávez, Marco Martín,González-Chávez, Rodolfo,Méndez, Francisco,Martínez, Roberto,Ni?o-Moreno, Perla Del Carmen,Ojeda-Fuentes, Luis Enrique,Richaud, Arlette,Zerme?o-Macías, María de los ángeles
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- Selective Debromination of α,α,α-Tribromomethylketones with HBr–H2O Reductive Catalytic System
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A debromination of α,α,α-tribromomethylketones is developed for chemoselective synthesis of α-mono- and α,α-dibromomethylketones with high selectivity under H2O–HBr reductive conditions. This method offers an efficient and direct way to synthesize α-mono or α,α-dibromomethylketone compounds in high to excellent yields through the process of HBr self-circulation in water.
- Cheng, Zhao,Guo, Hongmei,Huang, Guozheng,Rexit, Abulikemu Abudu,Wang, Hui,Zheng, Meng-Xia
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supporting information
p. 6455 - 6458
(2020/10/21)
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- Synthesis of 1,2-Dicyano-3-arylcycl[3.2.2]azines – First 1,2-Dicarbonitriles Based on Cyclazine Heterocycle
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The first 1,2-dicarbonitriles have been prepared for cyclazine systems. In particular, a synthetic procedure to 1,2-dicyano-3-arylcycl[3.2.2]azines has been developed. Unexpected chlorination of 3-arylcycl[3.2.2]azine-1,2-dicarboxylic acid derivatives by thionyl chloride at 4-position was found, which according to theoretical considerations can proceed by the electrophilic (SEAr) mechanism. The compounds are blue fluorophores in 450–480 nm region with quantum yields in toluene of ca. 30 % for non-chlorinated derivatives, which decrease to 3–4 % for chlorinated ones.
- Chernyak, Alexander V.,Kalashnikov, Valery V.,Kazachenko, Vladimir P.,Pushkarev, Victor E.,Simakov, Anton O.,Simonov, Sergey V.,Starikov, Andrei S.,Tarakanov, Pavel A.,Tkachev, Valery V.,Tomilova, Larisa G.,Yarkov, Alexander V.,Zhurkin, Fedor E.
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supporting information
p. 5852 - 5856
(2020/09/21)
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- Synthesis and Structure-Activity Relationship of Dual-Stage Antimalarial Pyrazolo[3,4- b]pyridines
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Malaria remains one of the most deadly infectious diseases, causing hundreds of thousands of deaths each year, primarily in young children and pregnant mothers. Here, we report the discovery and derivatization of a series of pyrazolo[3,4-b]pyridines targeting Plasmodium falciparum, the deadliest species of the malaria parasite. Hit compounds in this series display sub-micromolar in vitro activity against the intraerythrocytic stage of the parasite as well as little to no toxicity against the human fibroblast BJ and liver HepG2 cell lines. In addition, our hit compounds show good activity against the liver stage of the parasite but little activity against the gametocyte stage. Parasitological profiles, including rate of killing, docking, and molecular dynamics studies, suggest that our compounds may target the Qo binding site of cytochrome bc1.
- Eagon, Scott,Hammill, Jared T.,Sigal, Martina,Ahn, Kevin J.,Tryhorn, Julia E.,Koch, Grant,Belanger, Briana,Chaplan, Cory A.,Loop, Lauren,Kashtanova, Anna S.,Yniguez, Kenya,Lazaro, Horacio,Wilkinson, Steven P.,Rice, Amy L.,Falade, Mofolusho O.,Takahashi, Rei,Kim, Katie,Cheung, Ashley,Dibernardo, Celine,Kimball, Joshua J.,Winzeler, Elizabeth A.,Eribez, Korina,Mittal, Nimisha,Gamo, Francisco-Javier,Crespo, Benigno,Churchyard, Alisje,García-Barbazán, Irene,Baum, Jake,Anderson, Marc O.,Laleu, Beno?t,Guy, R. Kiplin
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p. 11902 - 11919
(2020/11/26)
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- 2-Amino-4-arylthiazoles through One-Pot Transformation of Alkylarenes with NBS and Thioureas
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Treatment of alkylarenes with N-bromosuccinimide in a mixture of ethyl acetate and water at 60 °C, a mixture of acetonitrile and water at 80 °C, or a mixture of diethyl carbonate and water under irradiation with a tungsten lamp, followed by a reaction with thioureas or arenethioamides provided the corresponding 2-amino- 4-arylthiazoles or 2,4-diarylthiazoles in good to moderate yields, respectively, in one pot. The present reaction is an efficient one-pot transformation method of alkylarenes into 2-amino-4-arylthiazoles and 2,4-diarylthiazoles directly under mild and transition-metal-free conditions.
- Shibasaki, Kaho,Togo, Hideo
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p. 2520 - 2527
(2019/04/04)
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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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- Microwave synthesis of 1-aryl-1H-pyrazole-5-amines
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A microwave-mediated synthesis of 1H-pyrazole-5-amines utilizing 1 M HCl at 150 °C was developed in order to provide products in a matter of minutes with minimal purification. Most reactions are complete in only 10 min and can be isolated via a simple filtration without the need for further purification by column chromatography or recrystallization. This method tolerates a range of functional groups and can be performed on milligram to gram scales.
- Everson, Nikalet,Yniguez, Kenya,Loop, Lauren,Lazaro, Horacio,Belanger, Briana,Koch, Grant,Bach, Jordan,Manjunath, Aashrita,Schioldager, Ryan,Law, Jarvis,Grabenauer, Megan,Eagon, Scott
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supporting information
p. 72 - 74
(2018/11/30)
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- Synthesis and Evaluation of 2-Azetidinone and 1H-Pyrrole-2,5-dione Derivatives as Cholesterol Absorption Inhibitors for Reducing Inflammation Response and Oxidative Stress
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Excess lipid accumulation can initiate the development and progression of atherosclerotic lesions, thus eventually leading to cardiovascular disease. Lipid-lowering medication therapy is one of the cornerstones of cardiovascular disease therapy. On the basis of the cholesterol absorption inhibitor ezetimibe, we successfully synthesized seven 2-azetidinone derivatives and eighteen 1H-pyrrole-2,5-dione derivatives. Most of the new compounds significantly inhibited cholesterol uptake in vitro. In addition, one of the most active inhibitors, 3-(4-fluorophenyl)-1-[(3S)-3-hydroxy-3-(4-hydroxyphenyl)propyl]-4-(4-hydroxyphenyl)-1H-pyrrole-2,5-dione (14q), showed no cytotoxicity in L02 and HEK293T cell lines. Further evaluation indicated that 14q inhibited considerably the amount of TNF-α, ROS, MDA, and LDH in vitro. Therefore, 14q might be a novel cholesterol absorption inhibitor.
- Xia, Yineng,Zhu, Lijuan,Yuan, Xinrui,Wang, Yubin
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- Diaryl-containing imidazole compound and preparation method and medical application thereof
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The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
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Paragraph 0138; 0139; 0140
(2019/02/21)
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- Organocatalytic Enantioselective Selenosulfonylation of a C-C Double Bond to Form Two Stereogenic Centers in an Aqueous Medium
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Organocatalytic selenosulfonylation of the C-C double bond of α,β-unsaturated ketones to construct two contiguous stereogenic centers in an aqueous medium was described. A series of α-selenyl and β-sulfonyl ketones with various functional groups were synthesized in good yields and enantioselectivities with saturated NaCl solution as the solvent. In addition, this protocol had been successfully scaled up to a decagram scale via a simple workup procedure.
- Chen, Zhili,Hu, Fangli,Huang, Shengli,Zhao, Zhengxing,Mao, Hui,Qin, Wenling
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p. 8100 - 8111
(2019/06/17)
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- One-Pot Preparation of Aromatic Amides, 4-Arylthiazoles, and 4-Arylimidazoles from Arenes
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Simple treatment of arenes with α-bromoacetyl chloride and AlCl3, followed by the reaction with molecular iodine and aq. NH3, thioamides, or amidines gave the corresponding primary aromatic amides, 4-arylthiazoles, or 4-arylimidazoles in good yields, respectively. Aryl α-bromomethyl ketones are the key intermediates in those reactions. Primary aromatic amides were formed from arenes through the reaction of aryl α-bromomethyl ketones with molecular iodine and aq. NH3, and 4-arylthiazoles and 4-arylimidazoles were formed from arenes through the reactions of aryl α-bromomethyl ketones with thioamides and amidines, respectively, in one pot under transition-metal-free conditions.
- Yamamoto, Takahiro,Togo, Hideo
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p. 4187 - 4196
(2018/08/21)
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- Synthesis of 2-aminothiazoles from styrene derivatives mediated by 1,3-dibromo-5,5-dimethylhydrantoin (DBH)
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An efficient procedure for the synthesis of 2-aminothiazoles via DBH-mediated oxidative cyclization of styrenes and thioureas is reported. Various alkenes were successfully transformed to the corresponding 2-aminothiazoles in yields of 10–81% via a two-step one-pot manner using DBH as both the bromine source and oxidant. The method can be readily carried out in gram-scale and successfully applied to the synthesis of anti-inflammatory drug fanetizole using styrene as starting material.
- Ma, Chunhua,Miao, Yuqi,Zhao, Minghao,Wu, Ping,Zhou, Jianglu,Li, Zhi,Xie, Xilei,Zhang, Wei
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p. 3602 - 3607
(2018/05/26)
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- Novel arylimino thiazole compound, preparation method and uses thereof
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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 0217; 0220; 0221; 0222
(2018/03/28)
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- Antibacterial synergist, preparation method and uses thereof
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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 0325; 0326; 0327; 0328
(2018/03/28)
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- Efficient sulfonylation of ketones with sodium sulfinates for the synthesis of β-keto sulfones
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The oxidative sulfonylation of ketones with sodium sulfinates as the sulfone source and DMSO as the oxidant is reported. A series of β-keto sulfones were obtained in good to excellent yields. The advantages of this efficient protocol include the low cost of DMSO and HBr, and a broad scope.
- Deng, Siqi,Liang, En,Wu, Yinrong,Tang, Xiaodong
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supporting information
p. 3955 - 3957
(2018/09/27)
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- A new and versatile one-pot strategy to synthesize alpha-bromoketones from secondary alcohols using ammonium bromide and oxone
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A new, efficient and green protocol for the one-pot synthesis of α-bromoketones from secondary alcohols using cheap, air stable and non-toxic reagents such as NH4Br and oxone has been developed. This reaction proceeds via two consecutive steps such as oxidation of secondary alcohols and oxidative bromination of in situ generated ketones.
- Rammurthy, Banothu,Swamy, Peraka,Naresh, Mameda,Srujana, Kodumuri,Durgaiah, Chevella,Krishna Sai, Gajula,Narender, Nama
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p. 3710 - 3714
(2017/07/12)
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- One-pot synthesis of α-bromo- and α-azidoketones from olefins by catalytic oxidation with in situ-generated modified IBX as the key reaction
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Simple one-pot protocols for the syntheses of α-bromoketones and α-azidoketones starting from olefins have been developed by employing catalytic oxidation of the intermediary bromohydrins with in situ-generated modified IBX as the key reaction. The improved procedure involves initial formation of bromohydrin by the reaction of olefin with NBS in acetonitrile-water mixture (1:1) at rt followed by oxidation with in situ-generated 3,4,5,6-tetramethyl-2-iodoxybenzoic acid (TetMe-IBX), produced in catalytic amounts from 3,4,5,6-tetramethyl-2-iodobenzoic and Oxone. α-Bromoketones are further converted in the same pot to the corresponding α-azidoketones using NaN3/NaHCO3. The one-pot conversions are versatile for a variety of olefins that include cyclic as well as acyclic aliphatic olefins and electron-rich and electron-deficient styrenes. Chemoselective bromohydroxylation of electron-rich double bond and subsequent oxidation to the α-bromoketone is demonstrated for a substrate that contains both electron-rich and deficient double bonds.
- Chandra, Ajeet,Parida, Keshaba Nanda,Moorthy, Jarugu Narasimha
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p. 5827 - 5832
(2017/09/09)
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- 1,3-Dibromo-5,5-dimethylhydantoin mediated oxidative amidation of terminal alkenes in water
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A variety of terminal alkenes were converted to the corresponding amides in yields of 25 to 86% in water via treatment with 1,3-dibromo-5,5-dimethylhydantoin, followed by reaction with molecular iodine and aq. NH3 (or amine) in one pot. This metal- and organic solvent-free protocol is not only suitable for styrene derivatives, but also, for the first time, works well on terminal aliphatic alkenes.
- Ma, Chunhua,Fan, Guojie,Wu, Ping,Li, Zhi,Zhou, Yang,Ding, Qingjie,Zhang, Wei
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p. 9889 - 9894
(2017/12/12)
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- TsNBr2mediated oxidative functionalization of alkynes
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A new approach has been developed for oxidative transformation of alkynes by controlled manipulation of TsNBr2mediated process. Alkynes could be readily converted to ketones and α-bromoketones via an oxybromination–debromination sequence. When alkynes are treated successively with TsNBr2, KI and Na2SO3in a mixture of acetone and water at room temperature, corresponding ketones were obtained. On the other hand, treatment of alkynes with TsNBr2and Na2SO3in a mixture of ethyl acetate, acetone and water at room temperature could produce corresponding α-bromoketones. 1-Bromoalkynes could also be synthesized from corresponding alkynes within a very short time using TsNBr2at room temperature. In all cases, excellent yields of corresponding products are obtained.
- Rajbongshi, Kamal Krishna,Hazarika, Debojit,Phukan, Prodeep
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p. 4151 - 4158
(2016/07/06)
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- First Catalyzed Hydration of Haloalkynes by a Recyclable Catalytic System
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The hydration of haloalkynes to give α-halomethyl ketones was achieved based on a combination of a Cu(OAc)2 catalyst and a TFA (trifluoroacetic acid) promoter. This is the first synthesis of chloro/bromo/iodo methyl ketones through a hydration reaction catalyzed by a recyclable catalytic system. The catalytic system has a wide substrate scope and excellent chemoselectivity, and the procedure can also be scaled up.
- Zou, Huaxu,He, Weibao,Dong, Qizhi,Wang, Ruijia,Yi, Niannian,Jiang, Jun,Pen, Dongming,He, Weimin
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p. 116 - 121
(2016/01/26)
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- Metal-free hydration of aromatic haloalkynes to α-halomethyl ketones
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A highly regioselective and efficient metal-free hydration of aromatic haloalkynes to α-halomethyl ketones using cheap tetrafluoroboric acid as catalyst is described. The protocol is conducted under convenient conditions and affords products in good to excellent yields, with broad substrate scope, including a variety of aromatic alkynyl chlorides, alkynyl bromides, and alkynyl iodides.
- Ye, Min,Wen, Yuelu,Li, Huifang,Fu, Yejuan,Wang, Qinghao
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supporting information
p. 4983 - 4986
(2016/10/21)
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- Highly Efficient Synthesis of α-Halomethylketones via Ce(SO4)2/Acid Co-Catalyzed Hydration of Alkynes
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A general atom-economical approach for the synthesis of α-halomethyl ketones is demonstrated through Ce(SO4)2/acid co-catalyzed hydration of a wide range of haloalkynes. The reactions are conducted under convenient conditions and provide products with excellent regioselectivity in good to excellent yields, with broad substrate scope. This protocol is an alternative to conventional α-halogenation of ketones.
- Zou, Huaxu,Jiang, Jun,Yi, Niannian,Fu, Wenqiang,Deng, Wei,Xiang, Jiannan
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supporting information
p. 1251 - 1254
(2016/12/27)
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- 1,3-Dibromo-5,5-dimethylhydantoin (DBH) mediated one-pot syntheses of α-bromo/amino ketones from alkenes in water
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α-Bromo ketones are versatile intermediates of high practical utility. Traditional approaches to these compounds are restricted to a relatively hazardous/complex reagent combination, a long reaction time, the use of non-environmentally friendly solvents, or a limited substrate scope. Herein, we describe the development of a new methodology for the preparation of α-bromo ketones from alkenes using 1,3-dibromo-5,5-dimethylhydantoin (DBH) as a bromine source and an oxidant simultaneously. This easy to carry out two-step one-pot protocol proceeds in water and provides high yield of a great variety of α-bromo ketones. Addition of an amine to the intermediate α-bromo ketone further enables the preparation of α-amino ketones in a one-pot sequence.
- Xu, Senhan,Wu, Ping,Zhang, Wei
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p. 11389 - 11395
(2016/12/18)
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- One pot synthesis of substituted imidazopyridines and thiazoles from styrenes in water assisted by NBS
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Heating of commercially available styrenes with NBS in water followed by reaction with 2-aminopyridines or thioamides afforded important heterocyclic scaffolds in a one pot procedure. The reaction proceeds via co-oxidant free, in situ formation of α-bromoketone using NBS as a bromine source as well as an oxidant followed by trapping with suitable nucleophiles to provide imidazopyridines and thiazoles.
- Shinde, Mahesh H.,Kshirsagar, Umesh A.
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supporting information
p. 1455 - 1458
(2016/04/04)
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- Metal-free protocol for the synthesis of α-bromo ketones from olefins using TsNBr2
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TsNBr2 reacts readily with olefins to produce α-bromo ketones at room temperature. The synthesis was carried out by treating an olefin with TsNBr2 in acetone-water mixture in 30:1 ratio. Excellent yield of corresponding α-bromo ketone could be achieved within a short time.
- Rajbongshi, Kamal Krishna,Hazarika, Debojit,Phukan, Prodeep
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supporting information
p. 356 - 358
(2015/04/27)
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- 2-(4-ARYL-1H-IMIDAZOL-1-YL)ANILINE COMPOUNDS
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The present invention provides compounds that are useful as vaccine adjuvants and/or antitumor agents and methods for producing and using the same. In one particular aspect of the invention, compounds of the invention are of the formula (I) where R1, R2, R3 and Ar1 are those defined herein.
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Paragraph 0094
(2015/11/27)
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- NITROGEN-CONTAINING CONDENSED HETEROCYCLIC COMPOUND
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There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: wherein Ring A represents a partially saturated heteroaryl group, an aryl group or a heteroaryl group, RB represents a C4-18 alkyl group, a C3-8 cycloalkyl group, a partially saturated aryl group, an aryl group, or the following formula (II): wherein V represents the formula -CR11R12-, -CO-, -CO-O-, or -CO-NH-, W represents a single bond or a C1-3 alkylene group, and Ring B represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a partially saturated heteroaryl group, a saturated heterocyclyl group, an aryl group, or a heteroaryl group, Y represents a nitrogen atom or the formula N+(RF), RF represents a C1-4 alkyl group, and m and n, which may be the same or different, each represent an integer of 0 or 1.
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- AgF/TFA-promoted highly efficient synthesis of α-haloketones from haloalkynes
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A AgF/TFA-promoted highly efficient synthesis of a wide range of α-haloketones from haloalkynes is described. The reactions are conducted under convenient conditions and provide products in moderate to excellent yields, with broad substrate scope, including a variety of aromatic chloroalkynes and bromoalkynes.
- Chen, Zheng-Wang,Ye, Dong-Nai,Ye, Min,Zhou, Zhong-Gao,Li, Shen-Huan,Liu, Liang-Xian
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supporting information
p. 1373 - 1375
(2014/03/21)
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- Structural design, synthesis and structure-activity relationships of thiazolidinones with enhanced anti-Trypanosoma cruzi activity
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Pharmacological treatment of Chagas disease is based on benznidazole, which displays poor efficacy when administered during the chronic phase of infection. Therefore, the development of new therapeutic options is needed. This study reports on the structural design and synthesis of a new class of anti-Trypanosoma cruzi thiazolidinones (4 a-p). (2-[2-Phenoxy-1-(4-bromophenyl) ethylidene)hydrazono]-5-ethylthiazolidin-4-one (4 h) and (2-[2-phenoxy-1-(4- phenylphenyl)ethylidene)hydrazono]-5-ethylthiazolidin-4-one (4 l) were the most potent compounds, resulting in reduced epimastigote proliferation and were toxic for trypomastigotes at concentrations below 10 μM, while they did not display host cell toxicity up to 200 μM. Thiazolidinone 4 h was able to reduce the in vitro parasite burden and the blood parasitemia in mice with similar potency to benznidazole. More importantly, T. cruzi infection reduction was achieved without exhibiting mouse toxicity. Regarding the molecular mechanism of action, these thiazolidinones did not inhibit cruzain activity, which is the major trypanosomal protease. However, investigating the cellular mechanism of action, thiazolidinones altered Golgi complex and endoplasmic reticulum (ER) morphology, produced atypical cytosolic vacuoles, as well as induced necrotic parasite death. This structural design employed for the new anti-T. cruzi thiazolidinones (4 a-p) led to the identification of compounds with enhanced potency and selectivity compared to first-generation thiazolidinones. These compounds did not inhibit cruzain activity, but exhibited strong antiparasitic activity by acting as parasiticidal agents and inducing a necrotic parasite cell death. Stop the cycle! The attachment of an aryl ring to the iminic carbon produced thiazolidinones that are conformationally more restricted than first-generation thiazolidinones. This enhanced the potency of antiparasitic thiazolidinones, as observed under treatment with compound 4 h where parasite development and invasion in host cells were substantially reduced. Copyright
- Moreira, Diogo Rodrigo Magalhaes,Lima Leite, Ana Cristina,Cardoso, Marcos Verissimo Oliveira,Srivastava, Rajendra Mohan,Hernandes, Marcelo Zaldini,Rabello, Marcelo Montenegro,Da Cruz, Luana Faria,Ferreira, Rafaela Salgado,De Simone, Carlos Alberto,Meira, Cassio Santana,Guimaraes, Elisalva Teixeira,Da Silva, Aline Caroline,Dos Santos, Thiago Andre Ramos,Pereira, Valeria Rego Alves,Pereira Soares, Milena Botelho
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supporting information
p. 177 - 188
(2014/01/17)
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- Gold-catalyzed hydration of haloalkynes to α-halomethyl ketones
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A general atom-economical approach for the synthesis of α-halomethyl ketones is demonstrated through hydration of a wide range of haloalkynes. Other outstanding features include excellent yields from both alkyl- and aryl-substituted haloalkynes and wide functional group tolerance. This protocol is an alternative to conventional α-halogenation of ketones.
- Xie, Longyong,Wu, Yundong,Yi, Weiguo,Zhu, Lei,Xiang, Jiannan,He, Weimin
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p. 9190 - 9195
(2013/10/08)
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- Synthesis of phenacyl bromides via K2S2O 8-mediated tandem hydroxybromination and oxidation of styrenes in water
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Non-transition metal-catalyzed synthesis of phenacyl bromides was achieved through K2S2O8-mediated tandem hydroxybromination and oxidation of styrenes. The advantages of this reaction are its excellent functional group compatibility, mild reaction conditions (60 °C) and use of pure water as reaction medium. Based upon experimental observations, a plausible reaction mechanism is proposed.
- Jiang, Qing,Sheng, Wenbing,Guo, Cancheng
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p. 2175 - 2179
(2013/09/24)
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- Palladium-catalyzed asymmetric hydrogenation of α-acyloxy-1- arylethanones
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First hand: The first example of a palladium-catalyzed asymmetric hydrogenation of α-acyloxy ketones (1) was accomplished to give the hydrogenated products 2 with by far the highest catalytic efficiency in up to quantitative conversions and excellent enantioselectivities. The hydrogenated products could serve as important intermediates for the preparation of many drug candidates. TFE=2,2,2-trifluoroethanol. Copyright
- Chen, Jianzhong,Liu, Delong,Butt, Nicholas,Li, Chao,Fan, Dongyang,Liu, Yangang,Zhang, Wanbin
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supporting information
p. 11632 - 11636
(2013/11/06)
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- Small molecule suppression of carbapenem resistance in ndm-1 producing klebsiella pneumoniae
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The already considerable global public health threat of multidrug-resistant Gram-negative bacteria has become even more of a concern following the emergence of New Delhi metallo-β-lactamase (NDM-1) producing strains of Klebsiella pneumoniae and other Gram-negative bacteria. As an alternative approach to the traditional development of new bactericidal entities, we have identified a 2-aminoimidazole-derived small molecule that acts as an antibiotic adjuvant and is able to suppress resistance of a NDM-1 producing strain of K. pneumoniae to imipenem and meropenem, in addition to suppressing resistance of other β-lactam nonsusceptible K. pneumoniae strains. The small molecule is able to lower carbapenem minimum inhibitory concentrations by up to 16-fold, while exhibiting little bactericidal activity itself.
- Worthington, Roberta J.,Bunders, Cynthia A.,Reed, Catherine S.,Melander, Christian
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p. 357 - 361
(2012/07/01)
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- Direct and selective benzylic oxidation of alkylarenes via C-H abstraction using alkali metal bromides
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A direct benzylic oxidation of alkylarenes via C-H bond abstraction was developed using alkali metal bromides and oxidants under mild conditions. This reaction proceeded with excellent selectivity by thermal oxidation or photooxidation to provide a broad range of carbonyl compounds containing electron-deficient aryl carbonyl compounds in high yields.
- Moriyama, Katsuhiko,Takemura, Misato,Togo, Hideo
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supporting information; experimental part
p. 2414 - 2417
(2012/06/18)
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- Easy access to α-bromoketones and epoxides from vic-dibromides under aqueous conditions
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The conversion of vic-1,2 dibromides to α-bromoketones and epoxides using H2O2/dioxane and NaOH/water respectively under mild conditions has been described. Copyright Taylor & Francis Group, LLC.
- Patil, Rajendra D.,Adimurthy, Subbarayappa,Ranu, Brindaban C.
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experimental part
p. 3233 - 3239
(2010/12/24)
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- Facile aerobic photo-oxidative synthesis of phenacyl iodides and bromides from styrenes using I2 or aqueous HBr
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We report a useful method for facile synthesis of phenacyl iodides and bromides from styrene derivatives by aerobic photo-oxidation using I2 or 48% aqueous HBr in the presence of water. Georg Thieme Verlag Stuttgart - New York.
- Nobuta, Tomoya,Hirashima, Shin-Ichi,Tada, Norihiro,Miura, Tsuyoshi,Itoh, Akichika
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experimental part
p. 2335 - 2339
(2010/11/04)
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- Synthesis and biological evaluation of 5-substituted and 4,5-disubstituted-2-arylamino oxazole TRPV1 antagonists
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The synthesis and structure-activity relationships of a series of 5-monosubstituted and 4,5-disubstituted 2-arylaminooxazoles as novel antagonists of the transient receptor potential vanilloid 1 (TRPV1) receptor are described. The 7-hydroxy group of the t
- Perner, Richard J.,Koenig, John R.,Didomenico, Stanley,Gomtsyan, Arthur,Schmidt, Robert G.,Lee, Chih-Hung,Hsu, Margaret C.,McDonald, Heath A.,Gauvin, Donna M.,Joshi, Shailen,Turner, Teresa M.,Reilly, Regina M.,Kym, Philip R.,Kort, Michael E.
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supporting information; experimental part
p. 4821 - 4829
(2010/08/06)
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- Facile one-pot synthesis of α-bromoketones from olefins using bromide/bromate couple as a nonhazardous brominating agent
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A new method for the preparation of α-bromoketones from olefins using bromide/bromate couple as a nonhazardous brominating agent has been developed. Several α-bromoketones were successfully prepared from a variety of olefins by this method. This procedure is an alternative to conventional molecular bromine.
- Patil, Rajendra D.,Joshi, Girdhar,Adimurthy, Subbarayappa,Ranu, Brindaban C.
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experimental part
p. 2529 - 2532
(2009/09/06)
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- ANTAGONISTS OF THE VANILLOID RECEPTOR SUBTYPE 1 (VR1) AND USES THEREOF
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The present invention is directed to compounds of formula (I) (I) wherein variables W, X, Y, D, A, n, R1, R2 and R9 are as defined in the description.
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Page/Page column 26
(2008/06/13)
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- A new approach to the synthesis of 2-aminoimidazo[1,2-a]pyridine derivatives through rapid parallel synthesis
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Different substituted 6-(2,6-difluorobenzoyl)-imidazopyridines 3 have been prepared using rapid parallel synthesis. Key cyanamide intermediate 4 was prepared from chloropyridine 1, and alkylated at the endocyclic nitrogen with different bromoacetophenones (prepared also in rapid parallel synthesis fashion). Subsequent cyclization was performed in situ with EtOAc/H2O to give target molecules.
- Jaramillo, Carlos,De Diego, J. Eugenio,Hamdouchi, Chafiq
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p. 1544 - 1546
(2007/10/03)
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- 3-O-Substituted benzyl pyridazinone derivatives as COX inhibitors
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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
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p. 339 - 347
(2007/10/03)
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- Antifungal amine derivatives and processing for producing the same
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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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- THERAPEUTIC AGENT FOR DIABETES
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A therapeutic agent for diabetes, which comprises a compound of the formula [I] wherein Xis a group of the formula wherein R4and R5are the same or different and each is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, and R6is a hydrogen atom or an amino-protecting group; R1is an optionally substituted alkyl having 1 to 5 carbon atoms, an optionally substituted alkenyl having 2 to 6 carbon atoms and the like, R2is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, R2' is a hydrogen atom, and R3is an optionally substituted alkyl having 1 to 5 carbon atoms and the like, a prodrug thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof and a solvate thereof. The compound of the present invention shows superior blood sugar decreasing action on the state of hyperglycemia, but does not affect the blood sugar when it is in the normal range or in the hypoglycemic state, which means that it is free of serious side effects such as hypoglycemia. Therefore, the compound of the present invention is useful as a therapeutic drug for diabetes and also useful as a preventive of the chronic complications of diabetes.
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- Imidazopyridazines. XV. Synthesis and Anxiolytic Activity of Some 3-(Benzamidomethyl and fluorobenzamidomethyl)-6-(fluoro, chloro and methylthio)-2-(4-tolyl and 3,4-methylenedioxyphenyl)imidazopyridazines
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Syntheses are reported for some 3-(benzamido- and fluorobenzamido-methyl)-6-(fluoro, chloro and methylthio)-2-(4-methyl-, 4-t-butyl-, 4-cyclohexyl- and 3,4-methylenedioxy-phenyl)imidazopyridazines from the relevant 3-unsubstituted imidazopyr
- Barlin, Gordon B.,Davies, Les P.,Glenn, Brok,Harrison, Peter W.,Ireland, Stephen J.
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p. 609 - 622
(2007/10/02)
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- Synthesis of 1,2-diamino imidazole derivatives by the reaction of benzaldehyde guanylhydrazone with α-haloalkyl aryl ketones
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2-Amino-1-benzylideneamino-4-arylimidazoles were obtained by the reaction of benzaldehyde guanylhydrazone with 4-alkyl- and 4-aryl-Ω-haloacetophenones. Side products of this reaction were cis- and trans-1,1′-bis(benzylideneamino)-4,4′-diaryl-2,2′-azoimida
- Ivashchenko,Lazareva,Prudnikova,Ivashchenko,Rumyantsev
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p. 185 - 189
(2007/10/02)
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