88419-56-1Relevant articles and documents
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
Chung, Sang J.,Kim, Dong H.
, p. 63 - 66 (1997)
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.
HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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Page/Page column 89, (2021/06/22)
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.
Cyano-and ketone-containing selenoesters as multi-target compounds against resistant cancers
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
, (2021/09/13)
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.
FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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Page/Page column 125; 126, (2021/06/22)
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).
Refining method of ciprofloxacin and meglumine hydrochloride thereof
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Paragraph 0026-0028, (2021/10/27)
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.
PROCESSES OF PREPARING A JAK1 INHIBITOR
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, (2021/12/17)
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.
Synthesis of Novel Ciprofloxacin-Based Hybrid Molecules toward Potent Antimalarial Activity
Dana, Srikanta,Dhar, Suman Kumar,Gurung, Sumiran Kumar,Kumar, Sharvan,Mondal, Neelima,Mukhopadhyay, Pritam,Valissery, Praveesh
supporting information, p. 1450 - 1456 (2020/08/14)
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.
Preparation method and purification method of 2, 4, 5-trifluorobenzoyl ethyl acetate
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Paragraph 0052-0057, (2021/01/15)
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.
Identification of an ethyl 5,6-dihydropyrazolo[1,5-c]quinazoline-1-carboxylate as a 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.
, (2020/04/02)
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.
DIHYDROOROTATE DEHYDROGENASE INHIBITORS
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Page/Page column 92, (2020/08/22)
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.
