- Synthesis and evaluation of 3-fluoro-2-piperazinyl-5,8,13-trihydro-5-oxoquino[1,2-a][3,1]benzoxazi ne-6-carboxylic acids as potential antibacterial agents
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3-Fluoro-2-piperazinyl-5,8,13-trihydro-5-oxoquino[1,2-a][3,1]-benzoxaz zine-6-carboxylic acids were designed and synthesized as potential DNA gyrase inhibitors and antibacterial agents. The design rationale rests on the proposition made by Ohta and Koga that in order for N1-aryl substituted quinolones to possess antibacterial activity the N1-aryl ring should be oriented out of the plane of the quinolone ring. α-[Bis(methylthio)methylene)-2,4,5-trifluoro-β-oxobenzenepropanoic acid tert-butyl ester (6) obtained by the treatment of 2,4,5-trifluoro-β-oxobenzenepropanoic acid tert-butyl ester (5) with carbon disulfide and methyl iodide in the presence of cesium carbonate was used as a key intermediate, yielding tert-butyl 2,3-difluoro-5,8,13-trihydro-5-oxoquino[1,2-a][1,3]benzoxazine-6-carbo xylate (8) upon treatment with 2-aminobenzyl alcohol. The coupling of 8 with piperazines followed by the hydrolysis of the ester under acidic conditions afforded the desired product (3). Contrary to expectation, both compounds (3a,b) were, however, devoid of antibacterial activity, suggesting that for N1-aryl substituted quinolones to exhibit antimicrobial activity important structural feature(s) other than the conformational requirement of the N1-aryl ring with respect to the quinolone nucleus should also be satisfied.
- Chung, Sang J.,Kim, Dong H.
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Read Online
- HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.
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Page/Page column 89
(2021/06/22)
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- Cyano-and ketone-containing selenoesters as multi-target compounds against resistant cancers
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Fifteen selenocompounds, comprising of eight ketone-containing selenoesters (K1–K8, also known as oxoselenoesters) and seven cyano-containing selenoesters (N1–N7, known also as cyanoselenoesters), have been designed, synthesized, and evaluated as novel anticancer agents. These compounds are derivatives of previously reported active selenoesters and were prepared following a three-step one-pot synthetic route. The following evaluations were performed in their biological assessment: cytotoxicity determination, selectivity towards cancer cells in respect to non-cancer cells, checkerboard combination assay, ABCB1 inhibition and inhibition of ABCB1 ATPase activity, apoptosis induction, and wound healing assay. As key results, all the compounds showed cytotoxicity against cancer cells at low micromolar concentrations, with cyanoselenoesters being strongly selective. All of the oxoselenoesters, except K4, were potent ABCB1 inhibitors, and two of them, namely K5 and K6, enhanced the activity of doxorubicin in a synergistic manner. The majority of these ketone derivatives modulated the ATPase activity, showed wound healing activity, and induced apoptosis, with K3 being the most potent, with a potency close to that of the reference compound. To summarize, these novel derivatives have promising multi-target activity, and are worthy to be studied more in-depth in future works to gain a greater understanding of their potential applications against cancer.
- Alonso-Martínez, Francisco-Javier,Benito-Lama, Miguel,Dobiasová, Simona,Domínguez-álvarez, Enrique,Habibullah, Giyaullah,Kincses, Annamária,Nové, Márta,Salardón-Jiménez, Noemi,Sevilla-Hernández, Clotilde,Spengler, Gabriella,Szemerédi, Nikoletta,Viktorová, Jitka
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- FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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The present invention relates to compound-linker constructs and antibody-drug-conjugates of compounds of formula (I) that are useful as modulators of STING (Stimulator of Interferon Genes).
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Page/Page column 125; 126
(2021/06/22)
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- Refining method of ciprofloxacin and meglumine hydrochloride thereof
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The invention provides a preparation process of ciprofloxacin and meglumine thereof. The intermediate product DLSX07 is stirred at Branson ° C. 20% minutes and then sonicated until the solution is cloudy, stirred at room temperature for a period 30s, stirred at room temperature 3h, cooled and slowly added to distilled water, and filtered through suction filtration and filter cake vacuum drying to obtain a pale yellow powder, and 4% the KOH mixture is subjected to ultrasonic treatment 40 - 50 °C. 1. The process is performed by stirring 5h. NCS .t. The solution is cloudy. LC-MS / MS detection powder is deltafloxacin, distilled water is added, and meglumine is mixed to obtain a deltafloxacin meglumine salt. By optimizing the preparation process, the use of the organic solvent is reduced, the reaction time is shortened, and the ice bath and the addition of the interface carrier material contribute to the improvement of the yield.
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Paragraph 0026-0028
(2021/10/27)
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- PROCESSES OF PREPARING A JAK1 INHIBITOR
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The present application provides processes for preparing 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H, 1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide, and phosphoric acid salt thereof, which is useful as a selective (Janus kinase 1) JAK1 inhibitor, as well as salt forms and intermediates related thereto.
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- Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity
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Antimalarial drug resistance is a serious obstacle in the persistent quest to eradicate malaria. There is a need for potent chemical agents that are able to act on drug-resistant Plasmodium falciparum populations at reasonable concentrations without any related toxicity to the host. By rational drug design, we envisaged to address this issue by generating a novel hybrid drug possessing two pharmacophores that can act on two unique and independent targets within the cell. We synthesized a new class of ciprofloxacin-based hybrid molecules, which have been integrated with acridine, quinolone, sulphonamide, and cinnamoyl pharmacophores (1-4). We realized a potent chloroquinolone-ciprofloxacin-based antimalarial hybrid (2, CQ-CFX) whose mechanism of action is unlike that of its parent molecules indicating a unique biological target. CQ-CFX is not only potent against CQ-resistant and susceptible strains of Plasmodium falciparum at low nanomolar concentrations (IC50 values are 63.17 ± 1.2 nM and 25.52 ± 4.45 nM, respectively) but is also not toxic to mammalian and bacterial systems up to 20 μM and 1 μM, respectively.
- Dana, Srikanta,Dhar, Suman Kumar,Gurung, Sumiran Kumar,Kumar, Sharvan,Mondal, Neelima,Mukhopadhyay, Pritam,Valissery, Praveesh
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supporting information
p. 1450 - 1456
(2020/08/14)
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- Preparation method and purification method of 2, 4, 5-trifluorobenzoyl ethyl acetate
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The invention relates to the field of organic synthesis, in particular to a preparation method and a purification method of 2, 4, 5-trifluorobenzoyl ethyl acetate. The method comprises the following steps: carrying out acylating chlorination reaction on 2, 4, 5-trifluorobenzoic acid and acyl chloride, continuously reacting with ethyl acetoacetate in a weakly alkaline solution to obtain an intermediate product, and heating the intermediate product to remove acetyl, thereby obtaining the 2, 4, 5-trifluorobenzoyl ethyl acetate. A one-pot method is adopted, operation is easy, only a small amount of waste residues are generated in the reaction process, and intramolecular hydrogen bonds and chelate structures are effectively avoided. The solvent can be recycled and reused, the method is economical, environmentally friendly, high in conversion rate and beneficial to industrial production, the invention further provides a purification method, impurities in the reaction process are effectivelyremoved, and the product with the purity larger than 99.5% is prepared.
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Paragraph 0052-0057
(2021/01/15)
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- Identification of an ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate as a catalytic inhibitor of DNA gyrase
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Fluoroquinolones are a class of antibacterial agents used clinically to treat a wide array of bacterial infections and target bacterial type-II topoisomerases (DNA gyrase and topoisomerase IV). Fluoroquinolones, however potent, are susceptible to bacterial resistance with prolonged use, which limits their use in the clinic. Quinazoline-2,4-diones also target bacterial type-II topoisomerases and are not susceptible to bacterial resistance similar to fluoroquinolones, however, their potency pales in comparison to fluoroquinolones. To meet the increasing demand for antibacterial development, nine modified quinazoline-2,4-diones were developed to probe quinazoline-2,4-dione structure modification for possible new binding contacts with the bacterial type-II topoisomerase, DNA gyrase. Evaluation of compounds for inhibition of the supercoiling activity of DNA gyrase revealed a novel ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate derivative as a modest inhibitor of DNA gyrase, having an IC50 of 3.5 μM. However, this ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate does not trap the catalytic intermediate like fluoroquinolones or typical quinazoline-2,4-diones do. Thus, the ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate derivative discovered in this work acts as a catalytic inhibitor of DNA gyrase and therefore represents a new structural type of catalytic inhibitor of DNA gyrase.
- Aguirre, Arturo L.,Chheda, Pratik R.,Groves, Natalie P.,Held, Hailey A.,Hiasa, Hiroshi,Kerns, Robert J.,Lentz, Sarah R. C.
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- DIHYDROOROTATE DEHYDROGENASE INHIBITORS
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Disclosed are compounds, compositions and methods for treating diseases, disorders, or medical conditions that are affected by the modulation of DHODH. Embodiments of such compounds are represented by Formula (I) as follows: 5 wherein R1, R2, R3, R4, R5a, R5b, X and Y, are defined herein.
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Page/Page column 92
(2020/08/22)
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- Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof
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Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.
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Paragraph 0136
(2021/01/22)
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- Synthesis and biological evaluation of N-acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors
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Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un-sulfated forms and promotes the growth of various hormone-dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid-sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N-acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4-(2-perfluoroundecanoylaminoethyl)-phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC50 value of 2.18?μm (IC50 value of 2.13?μm for coumarin-7-O-sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.
- Da?ko, Mateusz,Rachon, Janusz,Mas?yk, Maciej,Kubiński, Konrad,Demkowicz, Sebastian
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p. 156 - 161
(2017/06/19)
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- ANTIBACTERIAL COMPOUNDS AND NEW USES THEREOF
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This invention relates to a series of compounds of formula (I) for use in treating infections caused by obligate anaerobic bacteria, including Clostridium difficile, and to methods of treating said infections by administering said compounds. The compounds can be used against strains of obligate anaerobic bacteria that have developed resistance to other antibiotics. Many compounds used in the invention contain a tricyclic ring system.
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Page/Page column 90
(2017/04/11)
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- Design and synthesis of antimicrobial active new molecular entities of N-substituted pipradol derivatives
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Synthesis of antimicrobial 4-(hydroxyldiphenyl methyl)piperidin-1-yl)(substituted phenyl)methanone derivatives by using conventional chemical reactions to produces feasible and entirely new chemical entities (NCE’S) which were having a great potential microbial activities equivalent to fexofenidine used as a biological standard. This invention may help full for derive more potential pipradol molecules with peptide bond linkage.
- Sri Ramudu,Ramachandran,Venkat Rao,Murali Krishna,Satya Narayana,Reddy, Kallam Naveen
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p. 2113 - 2115
(2017/10/06)
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- Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control
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The photocatalytic C-F functionalization of highly fluorinated arenes is a powerful method for accessing functionalized multifluorinated arenes. The decisive step in the determining regioselectivity in fluorine functionalization is fluoride fragmentation from the radical anion of the multifluorinated arene. To date, the availability of regioisomers has been dictated by the innate electronics of the fluorinated arene, limiting the synthetic utility of the chemistry. This study investigates the remarkable ability of a strategically located hydrogen bond to transcend the normal regioselectivity of the C-F functionalization event. A significant rate acceleration is additionally observed for hydrodefluorination of fluorines that can undergo intramolecular hydrogen bonds that form 5-8-membered cycles with moderately acidic N-H's. The hydrogen bond is expected to facilitate the fragmentation not only by bending the C-F bond of the radical anion out of planarity but also by increasing the exothermicity of the fluoride extrusion step through protonation of the naked fluoride. Finally, the synthetic utility of the method is demonstrated in an expedited synthesis of the trifluorinated α-phenyl acetic acid derivative required for the commercial synthesis of Januvia, an antidiabetic drug. This represents the first synthesis of a commercially important multifluorinated arene via a defluorination strategy and is significantly shorter than the current strategy.
- Khaled, Mohammad B.,El Mokadem, Roukaya K.,Weaver, Jimmie D.
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supporting information
p. 13092 - 13101
(2017/09/26)
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- SURVIVAL BENEFIT IN PATIENTS WITH SOLID TUMORS WITH ELEVATED C-REACTIVE PROTEIN LEVELS
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This application relates to methods of increasing survival or progression-free survival in a patient with a solid tumor, wherein the patient has an elevated serum concentration of C-reactive protein (CRP), by administering a JAK inhibitor or an inhibitor of IL-6 signaling to the patient, as well as methods of predicting survival benefit in these patients from such therapy.
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Page/Page column 49; 50
(2015/03/13)
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- TREATMENT OF B-CELL MALIGNANCIES BY A COMBINATION JAK AND PI3K INHIBITOR
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This invention relates to methods of treating B-cell malignancies using a combination of inhibitors of JAK1 and/or JAK2 and inhibitors of PI3Kδ.
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Page/Page column 43
(2015/11/03)
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- ANTIBACTERIAL COMPOUNDS
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This invention relates to antibacterial and anti-mycobacterial drug compounds of formula I. It also relates to pharmaceutical formulations of antibacterial drug compounds. It also relates to uses of the derivatives in treating bacterial infections and to methods of treating bacterial infections. The invention is also directed to antibacterial drug compounds which are capable of treating bacterial infections which are currently hard to treat with existing drug compounds, e.g. those caused by resistant bacterial or mycobacterial strains.
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Page/Page column 96
(2015/11/17)
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- BICYCLIC HETEROARYLAMINOALKYL PHENYL DERIVATIVES AS PI3K INHIBITORS
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This application relates to derivatives of Formula I: and pharmaceutically acceptable salts thereof, which are inhibitors of PI3K, and compositions and methods of treatment related thereto.
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Paragraph 0371
(2015/12/30)
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- Novel fluoroquinolones and use thereof to treat bacterial infections
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The present invention relates to novel fluoroquinolones possessing a piperazine moiety substituted by a long alkyl chain, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.
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Paragraph 0053; 0055
(2016/01/12)
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- BIPYRAZOLE DERIVATIVES AS JAK INHIBITORS
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The present invention provides compounds of Formula I: or pharmaceutically acceptable salts thereof, as well as their compositions and methods of use, that inhibit the activity of Janus kinase (JAK) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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Paragraph 0447; 0448
(2014/12/09)
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- Synthesis of gatifloxacin derivatives and their biological activities against Mycobacterium leprae and Mycobacterium tuberculosis
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Novel 3′-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4-quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by 1H, 13C and 19F NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R8 and a secondary carbamate in R3′) and compound 5 (with a hydrogen in R8 and an ethyl ester in R3′) displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R3′ substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future.
- Gomez, Catherine,Ponien, Prishila,Serradji, Nawal,Lamouri, Aazdine,Pantel, Alix,Capton, Estelle,Jarlier, Vincent,Anquetin, Guillaume,Aubry, Alexandra
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p. 948 - 956
(2013/03/13)
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- N-AMINOSULFONYL BENZAMIDES
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The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to a new sulphonamide Nav 1.7 inhibitors of formula (I) or a pharmaceutically acceptable salt thereof, wherein Z, R1a, R1b, R2, R3, R4 and R5 are as defined in the description. Nay 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain
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Page/Page column 90
(2013/07/19)
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- Quinolone dimers as potential antibacterial agents
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A series of novel 6-fluoro1,4-dihydro-4-oxo-3-quinoline carboxylic acid dimers (34-37), were synthesized as potential antibacterial agents from commercially available fluoro benzoic acids.
- Chepyala, Naveenkumar R.,Durgi, Rajashaker R.,Tatini, Lakshmi K.,Subbaraju, Gottumukkala V.,Hindupur, Rama M.,Dhanvada, Muralimohan R.
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scheme or table
p. 637 - 643
(2012/06/01)
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- Enhancement of the antimalarial activity of ciprofloxacin using a double prodrug/bioorganometallic approach
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The derivatization of the fluoroquinolone ciprofloxacin greatly increases its antimalarial activity by combining bioorganometallic chemistry and the prodrug approach. Two new achiral compounds 2 and 4 were found to be 10- to 100-fold more active than ciprofloxacin against Plasmodium falciparum chloroquinesusceptible and chloroquine-resistant strains. These achiral derivatives killed parasites more rapidly than did ciprofloxacin. Compounds 2 and 4 were revealed to be promising leads, creating a new family of antimalarial agents.
- Dubar, Faustine,Anquetin, Guillaume,Pradines, Bruno,Dive, Daniel,Khalife, Jamal,Biot, Christophe
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scheme or table
p. 7954 - 7957
(2010/08/13)
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- 9-(HETEROARYL)-ISOTHIAZOLO[5,4-B]QUINOLINE-3,4-DIONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS
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The invention provides compounds and salts of Formula (I) and Formula (II); which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and/or selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.
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Page/Page column 45
(2010/11/30)
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- ANTIVIRAL AGENTS
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Compounds are provided having utility for the treatment of viral infections, particularly HCV.
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Page/Page column 67; Figure 10
(2010/11/29)
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- PREPARATION OF PYRIDONECARBOXYLIC ACID ANTIBACTERIALS
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A process for making 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, and therapeutically acceptable salts thereof, and intermediates used in the process are disclosed.
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Page/Page column 15
(2008/06/13)
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- Chlorination at the 8-position of a functionalized quinolone and the synthesis of quinolone antibiotic ABT-492
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The total synthesis of quinolone antibiotic ABT-492 has been achieved in 67% yield over nine steps from 2,4,5-trifluorobenzoic acid. The highlights of this synthesis include a novel chemoselective chlorination at the 8-position of a highly elaborated quinolone core. In addition, a Lewis acid promoted cyclization reaction to form the quinolone heterocycle was developed which was incorporated into a one-pot, three-step cyclization/coupling/protection sequence that proceeds in 93% yield.
- Barnes, David M.,Christesen, Alan C.,Engstrom, Kenneth M.,Haight, Anthony R.,Hsu, Margaret C.,Lee, Elaine C.,Peterson, Matthew J.,Plata, Daniel J.,Raje, Prasad S.,Stoner, Eric J.,Tedrow, Jason S.,Wagaw, Seble
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p. 803 - 807
(2012/12/22)
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- A convenient synthesis of n-substituted 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines in acidic conditions
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A novel and convenient synthesis of N-substituted 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines which possess potent in vitro inhibitory activity against gastric (H+/K+)-ATPase is reported. Compared with the methods reported previously, the compounds were synthesized more readily in relatively high yields by conversion of N-substituted 2-(benzyl-, 1-phenylethyl-, and benzhydrylsulfinyl)nicotinamides (17d-l) in a diluted hydrochloric acid-methanol solution at room temperature.
- Terauchi, Hideo,Tanitame, Akihiko,Tada, Keiko,Nishikawa, Yoshinori
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p. 1719 - 1734
(2007/10/03)
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- PREPARATION OF 1-HYDROXYXANTHEN-9(9H)-ONES AND 1-HYDROXYACRIDIN-9(10H)-ONES VIA CORRESPONDING 3,4-DIHYDRO-1,9(2H)-DIONES
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Target 10-cyclopropyl-7-fluoro-6-(4-methyl-1-piperazinyl)acridin-9(10H)-one (IVc) and 7-fluoro-1-hydroxy-6-(4-methyl-1-piperazinyl)-9H-xanthen-9-one (IVd) were obtained from corresponding difluoro derivatives IVa and IVb, respectively.These intermediates were synthesized via respective 3,4-dihydro-1,9(2H)-diones Va and Vb.Acridine derivative (10-cyclopropyl-6,7-difluoro-3,4-dihydro-1H-acridine-1,9(2H,10H)-dione, Va) was synthesized from 1-cyclopropyl-6,7-difluoroisatoic anhydride (XI) and xanthene derivative (6,7-difluoro-3,4-dihydro-1H-xanthen-1,9(2H)-dione, Vb) from cyclohexenone derivative VIb.Several unsuccessful attempts to prepare hydroxyacridone IVc and/or some useful intermediates of its synthesis are also described.
- Radl, Stanislav
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p. 2127 - 2136
(2007/10/03)
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- Synthesis of 1-substituted 3-nitroquinolin-4(1H)-ones
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A versatile synthetic method for preparing 1-substituted 3-nitroquinolin-4(1H)-ones from corresponding 2-fluoro-α-nitroacetophenones is demonstrated by the synthesis of 6,7-difluoro derivatives 7a-c. The method involves sequential treatment of the starting nitroacetophenone with triethyl orthoformate and the appropriate amine, followed by a nucleophilic cyclization reaction under mild conditions. The C-7 fluorine atom of 7 can be displaced by cyclic amines. Substituted 6-fluoro-7-(4-methy)-1-piperazinyl)-3-nitroquinolin-4(1H)-ones 8a-c were prepared in this way.
- Radl,Chan
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p. 437 - 440
(2007/10/02)
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- Synthesis, Antibacterial Activities, and Pharmacological Properties of Enantiomers of Temafloxacin Hydrochloride
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Temafloxacin hydrochloride is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent.It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group.The two enantiomers were synthesized and tested for their antibacterial activities.Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed.However, they both exhibited similar pharmacological profiles.
- Chu, Daniel T. W.,Nordeen, Carl W.,Hardy, Dwight J.,Swanson, Robert N.,Giardina, William J.,et al.
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p. 168 - 174
(2007/10/02)
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- 8-fluoro and 7,8,10-trifluoro-9-(substituted)-6-oxo-6H-benzo(C)quinolizine-5-carboxylic acids
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Novel substituted quinolinecarboxylic acid derivatives of the formula: STR1 wherein R1 is hydrogen, alkali metal, alkaline earth metal or lower alkyl; R2 is hydrogen, benzyl or alkyl(C1 -C3); X is hydrogen or fluoro; which have antibacterial activity, intermediates useful in the preparation of the compounds, methods of producing and using the compounds to treat bacterial infections in animals.
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- 7-(substituted)piperazinyl-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids
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7-(substituted)piperazinyl-1-ethyl-6-fluoro-4-oxo-3-quinolinecarboxylic acids, the pharmacologically acceptable salts thereof, compositions containing them, processes and intermediates for producing them, and methods of using them to treat bacterial infections in warm-blooded animals.
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- Quinolone Antibacterial Agents. Synthesis and Structure-Activity Relationships of 8-Substituted Quinoline-3-carboxylic Acids and 1,8-Naphthyridine-3-carboxylic Acids
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A series of 7,8-disubstituted 1-cyclopropyl-6-fluoroquinoline-3-carboxylic acids, 7-substituted 1-cyclopropyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids, and 10-substituted 9-fluoropyridobenzoxazine-6-carboxylic acids has been prepared and evaluated for antibacterial activity.The side chains examined at the 7-position (benzoxazine 10-position) included piperazinyl (g), 3-aminopyrrolidinyl (a), 3-(aminomethyl)pyrrolidinyl (b), and alkylated 3-(aminomethyl)pyrrolidinyl (c-f).Variations ta C-8 of the quinolone ring system included hydrogen, nitro, amino, fluorine and chlorine.The relative enhancement of in vitro activities by the side chains on the 8-hydrogen quinolone and 1,8-naphthyridine against Gram-negative organisms was a > b > g > c-f.The activity imparted to the substituted quinolone nucleus by the 8-substituent was in the order F > Cl > naphthyridine > H > benzoxazine > NH2 > NO2.These trends were retained in vivo.
- Sanchez, Joseph P.,Domagala, John M.,Hagen, Susan E.,Heifetz, Carl L.,Hutt, Marland P.,et al.
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p. 983 - 991
(2007/10/02)
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