- Conformationally constrained analogs of n-substituted piperazinylquinolones: Synthesis and antibacterial activity of n-(2,3-dihydro-4-hydroxyimino-4h-1-benzopyran-3-yl)-piperazinylquinolones
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A series of novel quinolone agents bearing a particular bulky and conformationally constrained bicyclic substituent (2,3-dihydro-4-hydroxyimino- 4H-1-benzopyran-3-yl- moiety) on the piperazine ring of 7-piperazinyl quinolones (norfloxacin, enoxacin, ciprofloxacin, and levofloxacin) were synthesized and evaluated against a panel of Gram-positive and Gram-negative bacteria. Among these derivatives, ciprofloxacin counterpart 9c, highly inhibited the tested Gram-positive bacteria, superior to that of the reference drugs, and displayed antibacterial activity at non-cytotoxic concentrations.
- Emami, Saeed,Foroumadi, Alireza,Samadi, Nasrin,Faramarzi, Mohammad A.,Rajabalian, Saeed
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Read Online
- 1,2-oxazinopyran compound, and preparation method and application thereof
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The invention provides a preparation method of a 1,2-oxazinopyran compound and a preparation method thereof. According to the preparation method for the compound, a pyrone compound is used as a substrate; a bromination reaction is conducted on the alpha-p
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Paragraph 0033-0035
(2020/08/30)
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- Chemoselective Hydrosilylation of the α,β-Site Double Bond in α,β- And α,β,γ,δ-Unsaturated Ketones Catalyzed by Macrosteric Borane Promoted by Hexafluoro-2-propanol
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The B(C6F5)3-catalyzed chemoselective hydrosilylation of α,β- and α,β,γ,δ-unsaturated ketones into the corresponding non-symmetric ketones in mild reaction conditions is developed. Nearly 55 substrates including those bearing reducible functional groups such as alkynyl, alkenyl, cyano, and aromatic heterocycles are chemoselectively hydrosilylated in good to excellent yields. Isotope-labeling studies revealed that hexafluoro-2-propanol also served as a hydrogen source in the process.
- Zhan, Xiao-Yu,Zhang, Hua,Dong, Yu,Yang, Jian,He, Shuai,Shi, Zhi-Chuan,Tang, Lei,Wang, Ji-Yu
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p. 6578 - 6592
(2020/07/17)
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- Enantioselective Total Syntheses of Pallambins A–D
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The first enantioselective total syntheses of (?)-pallambins A–D have been achieved in 15 or 16 steps from a known chiral cyclohexenone. Salient features of the syntheses include a palladium-catalyzed oxidative cyclization to assemble the [3.2.1]bicyclic moiety, an Eschenmoser–Claisen rearrangement/lactone formation sequence to construct the C ring, an intramolecular Wittig reaction to form the D ring, and individual transformations of pallambins C and D to generate pallambins A and B. The described synthesis avoids protecting-group manipulations through the design of highly chemo- and stereoselective transformations. During the course of this work, a palladium-catalyzed method for the dehydrobromination of α-bromoketones was developed, and the scope of this transformation was also investigated.
- Zhang, Xiwu,Cai, Xinxian,Huang, Bin,Guo, Lei,Gao, Zhongrun,Jia, Yanxing
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supporting information
p. 13380 - 13384
(2019/08/16)
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- Highly Enantioselective Synthesis of Fused Tri- and Tetrasubstituted Aziridines: aza-Darzens Reaction of Cyclic Imines with α-Halogenated Ketones Catalyzed by Bifunctional Phosphonium Salt
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The first enantioselective aza-Darzens reaction of cyclic imines with α-halogenated ketones was realized under mild reaction conditions by using amino-acid-derived bifunctional phosphonium salts as phase-transfer promoters. A variety of structurally dense tri- and tetrasubstituted aziridine derivatives, containing benzofused heterocycles as well as spiro-structures, were readily synthesized in high yields with excellent diastereo- and enantioselectivities (up to >20:1 d.r. and >99.9 % ee). The highly functionalized aziridine products could be easily transformed into different classes of biologically active compounds.
- Pan, Jianke,Wu, Jia-Hong,Zhang, Hongkui,Ren, Xiaoyu,Tan, Jian-Ping,Zhu, Lixiang,Zhang, Hong-Su,Jiang, Chunhui,Wang, Tianli
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supporting information
p. 7425 - 7430
(2019/05/10)
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- Synthesis of α,β-dibromo ketones by photolysis of α-bromo ketones with N-bromosuccinimide: Photoinduced β-bromination of α-bromo ketones
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Irradiation of α-bromopropiophenones in the presence of NBS results in the formation of α,β-dibromopropiophenones, which can be viewed as β-bromination of α-bromopropiophenones. The reaction is believed to go through a series of reactions; photoinduced C–Br bond cleavage, elimination of HBr to give α,β-unsaturated ketone intermediates, and addition of Br2, which are formed by the reaction between HBr and NBS. From mechanistic studies of the reaction, we have also found a very convenient method for α-debromination of the α,β-dibromopropiophenones which is by simple irradiation of the dibromo ketones in acetone or 2-propanol without the use of any additives. Our results demonstrate that bromine can be added into or eliminated from the alpha, beta, or both positions to the carbonyl group by photochemical methods, which make synthetic options of bromine containing carbonyl compounds versatile.
- Moon, Da Yoon,An, Sejin,Park, Bong Ser
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- MGLUR7 AGONIST COMPOUNDS FOR TREATING MGLUR7- REGULATED DISEASES, DISORDERS, OR CONDITIONS
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The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof wherein Z, R1, R2, R3, R4, R5 and R6 are as defined in the specification, a process for
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Paragraph 00178-00181
(2018/06/06)
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- Solvent free, light induced 1,2-bromine shift reaction of α-bromo ketones
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Photolysis of α-bromopropiophenones in acetonitrile results in formation of β-bromopropiophenones with good product selectivity, which can be coined as 1,2-Br shift reaction. The product selectivity increases when the reaction is done in neat or solid state, where only the 1,2-Br shift product is formed in some cases. The reaction is suggested to proceed by C–Br bond homolysis to give a radical pair, followed by disproportionation and conjugate addition of HBr to the α,β-unsaturated ketone intermediate. When the unsaturated intermediate is stabilized by an extra conjugation, the reaction stops at the stage, in which the unsaturated ketone becomes a major product. The synthetic method described in this research fits in a category of eco-friendly organic synthesis nicely since the reaction does not use volatile organic solvents and any other additives such as acid, base or metal catalysts, etc. Besides, the method fits into perfect atom economy, which does not give any side products. The synthetic method should find much advantage over other alternative methods to obtain β-bromo carbonyl compounds.
- An, Sejin,Moon, Da Yoon,Park, Bong Ser
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p. 6922 - 6928
(2018/10/24)
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- PPh3·HBr-DMSO: A Reagent System for Diverse Chemoselective Transformations
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The broad applicability of the hitherto unexplored reagent combination PPh3·HBr-DMSO is exemplified with multiple highly diverse one-step transformations to synthetically useful building blocks, such as flavones, 4H-thiochromen-4-ones, α-hydroxy ketones, 1,4-naphthoquinones (including vitamin K3), 2-bromo-3-substituted-1H-1-indenones, 2-methylthio-1H-1-indenones, 3-butyne-1,2-dione, and 4-pentene-2,3-diones. The simple and mild reaction conditions make the reagent superior in terms of yield and substrate scope in comparison with the existing alternatives.
- Mal, Kanchan,Kaur, Amanpreet,Haque, Fazle,Das, Indrajit
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p. 6400 - 6410
(2015/06/30)
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- Imidazolylchromanones containing non-benzylic oxime ethers: Synthesis and molecular modeling study of new azole antifungals selective against Cryptococcus gattii
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A series of imidazolylchromanone oximes containing phenoxyethyl ether moiety, as found in omoconazole, were synthesized and evaluated against yeasts (Candida albicans and Cryptococcus gattii) and filamentous fungi (Aspergillus fumigatus and Exophiala derm
- Babazadeh-Qazijahani, Mojtaba,Badali, Hamid,Irannejad, Hamid,Afsarian, Mohammad Hosein,Emami, Saeed
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p. 264 - 273
(2014/03/21)
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- Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application
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The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1-22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe-Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R3) at the para-position of the P1′ benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R1) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16-22) with EC50s on wild-type HIV-1 in the range of 0.8-1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS.
- Kesteleyn, Bart,Amssoms, Katie,Schepens, Wim,Hache, Geerwin,Verschueren, Wim,Van De Vreken, Wim,Rombauts, Klara,Meurs, Greet,Sterkens, Patrick,Stoops, Bart,Baert, Lieven,Austin, Nigel,Wegner, J?rg,Masungi, Chantal,Dierynck, Inge,Lundgren, Stina,J?nsson, Daniel,Parkes, Kevin,Kalayanov, Genadiy,Wallberg, Hans,Rosenquist, ?sa,Samuelsson, Bertil,Van Emelen, Kristof,Thuring, Jan Willem
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p. 310 - 317
(2013/02/25)
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- Nickel - promoted favorskii type rearrangement of cyclic α-bromoketones
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Favorskii type rearrangement of cyclic α-bromo ketones 2 is promoted by NiCl2 in refluxing methanol, giving the rearranged carboxylic acid ester 3 in excellent yields. The reaction of 4-bromo-2,3,4,5-tetrahydronaphth [2,1-b]oxepin-5-one (5) and its regioisomer 8 with NiCl2 in McOH resulted in Favorskii rearranged carboxylic acid esters 6 and 9 respectively.
- Tandon, Vishnu K.,Awasthi, Anoop K.,Singh, Kunwar A.,Maurya, Hardesh K.,Gautam, Sanjay K.
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experimental part
p. 593 - 600
(2010/04/27)
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- KHMDS enhanced SmI2-mediated reformatsky type α-cyanation
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A novel combination of SmI2, KHMDS, and TsCN can be utilized to introduce a cyano group into structurally diverse and highly sensitive 2-alkyl-chroman-4-ones. Subsequent oxidation allows the formed 2-alkyl-3-cyanochromones to be isolated in yields ranging from 49 to 77%. In addition, α-bromoketones and esters were found to undergo equally effective α-cyanation.
- Ankner, Tobias,Friden-Saxin, Maria,Pemberton, Nils,Seifert, Tina,Grotli, Morten,Luthman, Kristina,Hilmersson, Goeran
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supporting information; experimental part
p. 2210 - 2213
(2010/08/04)
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- Gamma-hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides and uses thereof
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γ-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamide compounds are inhibitors of HIV protease and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. These compounds are effective against HIV viral mutants which are resistant to HIV protease inhibitors currently used for treating AIDS and HIV infection.
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Page/Page column 82
(2010/01/31)
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- Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains
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Indinavir analogues with blocked metabolism sites show highly improved pharmacokinetic profiles in animals. The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains.
- Cheng, Yuan,Zhang, Fengqi,Rano, Thomas A,Lu, Zhijian,Schleif, William A,Gabryelski, Lori,Olsen, David B,Stahlhut, Mark,Rutkowski, Carrie A,Lin, Jiunn H,Jin, Lixia,Emini, Emilio A,Chapman, Kevin T,Tata, James R
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p. 2419 - 2422
(2007/10/03)
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- Base-induced coupling of α-azido ketones with aldehydes -an easy and efficient route to trifunctionalized synthons 2-azido-3-hydroxy ketones, 2-acylaziridines, and 2-acylspiroaziridines
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An improved synthesis of a-azido ketones under phase-transfer conditions has been developed. The transformation of α-azido ketones into acyclic and heterocyclic 2-azido-3-hydroxy ketones has been demonstrated and the relative configurations of the chroman
- Patonay, Tamas,Juhasz-Toth, Eva,Benyei, Attila
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p. 285 - 295
(2007/10/03)
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- A comparative study on the inhibition of human and bacterial kynureninase by novel bicyclic kynurenine analogues
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A series of novel bicyclic analogues of kynurenine were synthesised as inhibitors of kynureninase. The trytophan-induced bacterial enzyme from Pseudomonas fluorescens were compared to the constitutive recombinant human enzyme expressed in a baculovirus/insect cell system, with regard to their inhibition by these compounds. All the compounds studied were found to be simple competitive, reversible inhibitors of kynureninase. It was found that altering the size of the second ring of the inhibitor affected the observed Ki values for both enzymes. The addition of an oxygen atom into the second ring had little effect on binding to the bacterial enzyme but gave a more potent inhibitor of human kynureninase. Of the compounds tested, a naphthyl analogue of desaminokynurenine was found to be the most potent inhibitor for both enzymes with Ki values of 5 and 22 μM for bacterial and human enzyme respectively. This report also describes an alternative system for the expression of recombinant human kynureninase which is more convenient for expression in mammalian cells and produces a relatively greater quantity of enzyme. Copyright
- Fitzgerald, Deirdre H.,Muirhead, Karen M.,Botting, Nigel P.
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p. 983 - 989
(2007/10/03)
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- Pyrrole derivatives and medicinal composition
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The invention relates to a pharmaceutical composition comprising a pyrrole derivative of the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate of either of them, as an active ingredient. STR1 (wherein R1 represents hydrogen or alkoxycar91 bonylamino, R2 represents alkyl, aryl which may be substituted, aromatic heterocyclyl which may be substituted, unsubstituted amino, monoalkylamino, dialkylamino, or cyclic amino which may be substituted; R3 represents cyano or carbamoyl; R4 represents hydrogen or alkyl; E represents alkylene; q is equal to 0 or 1, A represents methyl, aryl which may be substituted, or aromatic heterocyclyl which may be substituted). The pharmaceutical composition of the invention is effective for the treatment of pollakiuria or urinary incontinence.
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- 1,2,3,4-tetrahydronaphthalene compounds
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R1 and R2 form, with the carbon atoms to which they are attached, cyclopentane or cyclohexane, R3 represents hydroxyl, linear or branched (C1 -C6) alkoxy or unsubstituted or substituted amino,
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- Aromatic Annelation with α-Phenylsulfinyl-γ-butyrolactones. A Novel Route to 4-(2-Hydroxyalkyl)-1,3-benzenediols
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A number of 4-(2-hydroxyalkyl)-1,3-benzenediols (4) were synthesized by thermolysis of 1,3-cyclohexadiones (3), wich were obtained by the reaction of α-phenylsulfinyl-γ-butyrolactones (1) with α,β-unsaturated ketones (2), providing a new aromatic annelati
- Ozaki, Yutaka,Mochida, Keiko,Kim, Sang-Won
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p. 1790 - 1795
(2007/10/02)
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