- Optimization of biaryloxazolidinone as promising antibacterial agents against antibiotic-susceptible and antibiotic-resistant gram-positive bacteria
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We previously discovered a series of novel biaryloxazolidinone analogues bearing a hydrazone moiety with potent antibacterial activity. However, the most potent compound OB-104 exhibited undesirable chemical and metabolic instability. Herein, novel biaryloxazolidinone analogues were designed and synthesized to improve the chemical and metabolic stability. Compounds 6a-1, 6a-3, 14a-1, 14a-3 and 14a-7 showed significant antibacterial activity against the tested Gram-positive bacteria as compared to radezolid and linezolid. Further studies indicated that most of them exhibited improved water solubility and chemical stability. Compound 14a-7 had MIC values of 0.125–0.25 μg/mL against all tested Gram-positive bacteria, and showed excellent antibacterial activity against clinical isolates of antibiotic-susceptible and antibiotic-resistant bacteria. Moreover, it was stable in human liver microsome. From a safety viewpoint, it showed non-cytotoxic activity against hepatic cell and exhibited lower inhibitory activity against human MAO-A compared to linezolid. The potent antibacterial activity and all these improved drug-likeness properties and safety profile suggested that compound 14a-7 might be a promising drug candidate for further investigation.
- Wu, Yachuang,Ding, Xiudong,Yang, Yifeng,Li, Yingxiu,Qi, Yinliang,Hu, Feng,Qin, Mingze,Liu, Yajing,Sun, Lu,Zhao, Yanfang
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- Synthesis and antibacterial activity evaluation of novel biaryloxazolidinone analogues containing a hydrazone moiety as promising antibacterial agents
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A series of linezolid analogues containing a hydrazone moiety were designed, synthesized and evaluated for their antibacterial activity. Most compounds exhibited more potent antibacterial activity against S.aureus, MRSA, MSSA, LREF and VRE pathogens as compared with linezolid and radezolid. Compounds 9a, 9c, 9f, 9g, 10m and 10t were more potent against tested clinical isolates of MRSA, MSSA, VRE and LREF as compared to linezolid. Compound 9a exhibited comparable activity with linezolid against human MAO-A for safety evaluation and showed moderate metabolism in human liver microsome. The most promising compound 9a showed remarkable antibacterial activity against S.aureus, MRSA, MSSA, LREF and VRE pathogens with MIC value of 0.0675 mg/mL, respectively, which was 15- to 30-fold more potent than linezolid.
- Wu, Yachuang,Ding, Xiudong,Ding, Liang,Zhang, Yongsheng,Cui, Lei,Sun, Lu,Li, Wei,Wang, Di,Zhao, Yanfang
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p. 247 - 258
(2018/09/18)
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- Nodulisporic acid derivatives
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The present invention relates to novel nodulosporic acid derivatives, which are acaricidal, antiparasitic, insecticidal and anthelmintic agents.
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- Aza-enamines, VIII. - Electrophilic Substitution reactions at the Azomethine C-Atom of Aldehyde Dialkylhydrazones: Vilsmeier Formylation and Consecutive Reactions
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The reaction of hydrazones 1 with the Vilsmeier reagent yields 3-phenyl-1,4,5-triaza-1,3-pentadienium salts according to their aza-enamine character.Hydrolysis of 2 gives 1-phenylglyoxal 1-dialkylhydrazones 3, which rearrange in acidic media to 1-phenylglyoxal 2-dialkylhydrazones 4.Compound 3h forms the dihydropyrroloimidazole 5 in boiling ethanol.Pyrrolotriazinium salt 6 is obtained by the reaction of 1b with the isolated Vilsmeier reagent from dimethylformamide/oxalyl chloride.
- Brehme, Rainer
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p. 2039 - 2046
(2007/10/02)
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- SYNTHESIS OF 4-METHOXYPHENOXYACETIC AND 3,4,5-TRIMETHOXYPHENOXYACETIC ACID AMIDES AND HYDRAZIDES AS POTENTIAL NEUROTROPIC AND CARDIOVASCULAR AGENTS
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4-Methoxyphenoxyacetyl chloride, 3,4,5-trimethoxyphenoxyacetic acid and its methyl ester were reacted with 2-phenylethylamine, 1-benzylpiperazine, 1-(2-phenylethyl)piperazine, 1-(1-phenyl-2-propyl)piperazine, isopropylhydrazine, 1-aminopiperidine, and 4-aminomorpholine and afforded the amides and hydrazides Iab-IVab and Vb-VIIIb. 1-Amino-4-methylpiperazine and 1-amino-4-phenylpiperazine were transformed to the hydrazones XV and XVI, and to the quaternary salts XVII and XVIII.Pharmacological screening showed indications of thymoleptic acitivity with compounds Ia-IIIa, anorectic effect with IIa and IIIb, antiarrhytmic activity with IIIa, XVII, and XVIII, and myorelaxant effect with XVII and XVIII.Antimicrobial and anthelmintic effects were also noted.
- Valenta, Vladimir,Holubek, Jiri,Svatek, Emil,Protiva, Miroslav
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p. 3013 - 3023
(2007/10/02)
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- Preparation of N-amino compounds
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Disclosed is a method of preparing N-amino compounds from corresponding secondary amines by reacting a secondary amine with nitrous acid and zinc in a neutral pH reaction media to form the corresponding N-amine.
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- 3-aryl-7-chloro-3,4-dihydroacridine-1,9(2H,10H)-dione 1-oximes and 1-hydrazone derivatives, their salts, a process for their preparation, agents containing them and their use
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3-Aryl-7-chloro-3,4-dihydroacridine-1,9(2H,10H)-dione 1-oximes and 1-hydrazone derivatives of the formula I STR1 and their physiologically tolerated acid addition and ammonium salts are described, as is a process for their preparation. The new compounds are chemotherapeutic agents and are active against protozoa, especially malaria plasmodia.
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- MANY-ELECTRON ELECTRODE PROCESSES. XIII. PRODUCTS OF THE ELECTROLYSIS OF N-NITRO AND N-NITROSO AMINES
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A study was made of the factors influencing the relative yields of the corresponding amines and hydrazines in the reduction of 4-nitro- and 4-nitroso-morpholines and N-nitrosodiphenylamine in DMF and acetonitrile in presence of acetic and benzoic acids.The relative yield of the hydrazine in the reduction of N-nitroso amines rises with rise in the concentration of the carboxylic acid, rise in the basicity of the amine nitrogen atom in the depolarizer molecule, and fall in the basicity of the organic solvent.
- Krgin, Yu. M.,Latypova, V. Z.,Supyrev, A. V.,Zhuikov, V. V.
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p. 1510 - 1513
(2007/10/02)
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- Reduction of Nitrosamines with Aqueous Titanium Trichloride: Convenient Preparation of Aliphatic Hydrazines
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The reduction of selected nitrosamines by aqueous TiCl3 has been investigated.In general, aliphatic nitrosamines were converted in good yield to the corresponding hydrazines, with little overreduction to the amines.Reaction proceeded rapidly at room temperature in both alkaline and acidic media.A variety of N,N-dialkylhydrazines have been isolated by using the TiCl3 method, which compares favorably with previously reported procedures for preparatively converting nitrosamines to hydrazines.In the reduction of N-nitroso-N-methylaniline, the proportion of amine in the product increased significantly as the pH of the reaction mixture was lowered, presumably reflecting the known instability of arylalkylnitrosamines in strong acid, coupled with a ready reducibility of the corresponding Fischer-Hepp intermediates; some tendency toward reductive cleavage of the N-aryl-N-alkylhydrazine's N-N-bond was also noted.Reduction of an α-nitrosamino ether gave the monoalkylhydrazine as the major product, while all other reducing agents studied converted this starting material chiefly to a mixture of primary and secondary amines.
- Lunn, George,Sansone, Eric B.,Keefer, Larry K.
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p. 3470 - 3473
(2007/10/02)
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- Organic compounds substituted heptadeca-5,9- and 5,10-dienoic acid
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The present invention provides novel substituted heptadeca-5,9- and 5,10-dienoic acid and similar fatty acid compounds which are derivatives of certain prostaglandins and are potent thromboxane A2 inhibitors. By virtue of this pharmacological property, they represent useful pharmacological agents for a wide variety of purposes.
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