- Synthesis and potential antimicrobial activity of novel α-aminophosphonates derivatives bearing substituted quinoline or quinolone and thiazole moieties
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To develop novel antimicrobial agents, and based on the biologically active heterocyclic quinoline and thiazole substituted, a series of novel α-aminophosphonates (9a–h) and (10i–l) derivatives that incorporated quinoline or quinolone, and coumarylthiazole or 5-phenylthiazol-2-amine moieties were designed and synthesized via Kabachnik–Fields reaction in the presence of ionic liquid under ultrasound irradiation. All the new compounds were obtained in good yield with a simple workup and were confirmed using various spectroscopic methods. The in vitro antimicrobial activity of all synthesized compounds were screened in terms of MIC values against the selected strains of Gram-negative and Gram-positive bacteria and two fungal strains using the broth micro-dilution method. The results showed that most of the tested compounds showed moderate inhibitory activities against both Gram‐positive and ‐negative bacteria compared with reference drugs. The following compounds 9e, 9g, 9h, 9i and 9f, 9g, 9h, 10k, 10l are the most active against Gram-positive and Gram-negative bacteria strains, respectively, with MIC values ranging between 0.25 and 128 μg/mL. The synthesized compounds 9b, 9c, 9f, 9g, 9h, 10k, and 10l exhibited excellent antifungal inhibition with MIC values ranging between 0.25 and 32 μg/mL. Structure–activity relationship revealed that the presence of coumarylthiazole moiety and hydroxyl in the quinoline group increased the inhibitory activity against microbial strains pathogens. These results confirm that the synthesized compounds can be potential antimicrobial drugs candidate. [Figure not available: see fulltext.]
- Litim, Bilal,Djahoudi, Abdelghani,Meliani, Saida,Boukhari, Abbes
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- Identification of 5-Substituted 2-Acylaminothiazoles That Activate Tat-Mediated Transcription in HIV-1 Latency Models
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The persistent reservoir of cells latently infected with human immunodeficiency virus (HIV)-integrated proviral DNA necessitates lifelong suppressive antiretroviral therapy (ART). Epigenetic targeted compounds have shown promise as potential latency-reversing agents; however, these drugs have undesirable toxicity and lack specificity for HIV. We utilized a novel HEK293-derived FlpIn dual-reporter cell line, which quantifies specific HIV provirus reactivation (LTR promoter) relative to nonspecific host cell gene expression (CMV promoter), to identify the 5-substituted 2-acylaminothiazole hit class. Here, we describe the optimization of the hit class, defining the functionality necessary for HIV gene activation and for improving in vitro metabolism and solubility. The optimized compounds displayed enhanced HIV gene expression in HEK293 and Jurkat 10.6 latency cellular models and increased unspliced HIV RNA in resting CD4+ T cells isolated from HIV-infected individuals on ART, demonstrating the potential of the 2-acylaminothiazole class as latency-reversing agents.
- Nguyen, William,Jacobson, Jonathan,Jarman, Kate E.,Jousset Sabroux, Helene,Harty, Leigh,McMahon, James,Lewin, Sharon R.,Purcell, Damian F.,Sleebs, Brad E.
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p. 5148 - 5175
(2019/05/28)
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- Glucose promoted facile reduction of azides to amines under aqueous alkaline conditions
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A quick and efficient method for the reduction of azides to amines in water using d-glucose and KOH as green reagents is reported. The protocol is simple, inexpensive, scalable, and can be applied to different aromatic, heteroaromatic and sulphonyl azides. A high level of chemoselectivity is observed for azide reduction in the presence of other reducible functionalities like cyano, nitro, ether, ketone, amide and acid. The reaction gets completed in a short time (5-20 minutes), and furnishes the amines in high yield (85-99%). Unlike conventional hydrogenations, this reduction protocol does not require any metal catalyst, elaborate experimental setup or use of high-pressure equipment.
- Chandna, Nisha,Kaur, Fatehjeet,Kumar, Shobhna,Jain, Nidhi
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supporting information
p. 4268 - 4271
(2017/09/29)
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- Silver-Catalyzed Regio- and Stereoselective Thiocyanation of Haloalkynes: Access to (Z)-Vinyl Thiocyanates
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A regio- and stereoselective method for the preparation of (Z)-vinyl thiocyanate derivatives by silver-catalyzed thiocyanation of haloalkynes is reported. This method features practical, free of ligand, broad substrate scope, excellent stereoselectivity and gram-scale synthesis. Significantly, the halogen atom of haloalkynes is retained, which allows the synthesis of 2,5-diphenylthiophene, thiazol-2-amine and trifluoromethyl sulfides derivatives via simple transformation. (Figure presented.).
- Jiang, Guangbin,Zhu, Chuanle,Li, Jianxiao,Wu, Wanqing,Jiang, Huanfeng
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p. 1208 - 1212
(2017/04/11)
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- Novel 2-Aminothiazole Derivatives and Composition for Treating Cancer Comprising the Same
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PURPOSE: A novel 2-aminothiazole derivative and an anticancer composition containing the same are provided to suppress growth and proliferation of various cancer cells and to induce cancer cell apoptosis. CONSTITUTION: A 2-aminothiazole derivative is denoted by chemical formula 1. In chemical formula 1, R1 is phenyl, halogen-substituted phenyl, alkyl of 1-4 carbon atoms, or phenyl-substituted alkyl of C1-4; and R2 is alkyl of C1-9, furyl-substituted alkyl of C1-4, furyl-substituted alkenyl of C1-4. An anticancer composition contains the 2-aminothiazole derivative of chemical formula 1 or pharmaceutically acceptable salt thereof as an active ingredient. The anticancer composition is a pharmaceutical composition for preventing or treating cancer.
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Paragraph 0052-0054
(2017/06/06)
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- Identification of KPNB1 as a Cellular Target of Aminothiazole Derivatives with Anticancer Activity
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We found that aminothiazole derivative (E)-N-(5-benzylthiazol-2-yl)-3-(furan-2-yl)acrylamide (1) has strong anticancer activity, and undertook proteomics approaches to identify the target protein of compound 1, importin β1 (KPNB1). A competitive binding assay using fluorescein-labeled 1 showed that 1 has strong binding affinity for KPNB1 (Kd: ~20 nm). Furthermore, through western blotting assays for KPNB1, KPNA2, EGFR, ErbB2, and STAT3, we confirmed that 1 has inhibitory effects on the importin pathway. KPBN1 appears to be overexpressed in several cancer cells, and siRNA-induced inhibition of KPNB1 shows significant inhibition of cancer cell proliferation, while leaving non-cancerous cells unaffected. Therefore, compound 1 is a promising new lead for the development of KPNB1-targeted anticancer agents. Fluorescein-labeled 1 could be a useful quantitative probe for the development of novel KPNB1 inhibitors.
- Kim, Yong-Hak,Ha, Siyoung,Kim, Jungwon,Ham, Seung Wook
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supporting information
p. 1406 - 1409
(2016/07/16)
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- HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
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ABSTRACT The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
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Paragraph 000319
(2015/10/05)
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- NOVEL KINASE INHIBITORS
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The present invention provides derivatives of thiazolylamino-substituted heterocycles. These compounds are inhibitors of kinases, including compounds that show antiproliferative activity against cells, including against tumor cells, and are useful in the treatment of diseases including cancer.
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Paragraph 0210
(2014/05/07)
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- BENZYL SUBSTITUTED TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
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The invention provides triazine compounds and methods of their use to modulate protein kinases and to treat diseases mediated by said protein kinases.
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Page/Page column 69
(2010/12/29)
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- TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS
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The invention provides Triazine derivatives and further provides methods of using these compounds to modulate protein kinases and for treating diseases and conditions mediated by protein kinases.
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Page/Page column 68
(2010/12/29)
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- HETEROCYCLIC KINASE MODULATORS
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The present disclosure provides heterocyclic protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.
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Page/Page column 111
(2009/01/20)
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- ABCA-1 elevating compounds
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The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.
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- Phototransposition chemistry of phenylisothiazoles and phenylthiazoles. 1. Interconversions in benzene solution
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Phenylthiazoles 1-3 and phenylisothiazoles 4-6 undergo phototransposition in benzene solvent mainly by P5, P6, and P7 permutation pathways. Phenylisothiazoles 5 and 6 also transpose via a P4 permutation process to yield phenylthiazoles 2 and 3 in less than 1% yield. In benzene saturated with D2O, 2-phenylthiazole (1) and 5-phenylisothiazole (6) each phototranspose to yield 4-deuterio-3-phenylisothiazole (4-D-4) and 4-phenylthiazole (2) without deuterium incorporation. Irradiation of 4-phenylthiazole (2) under these conditions results in rapid photodeuteration to yield 2-deuterio-4-phenylthiazole (2-D-2), which subsequently phototransposes to 5-deuterio-3-phenylisothiazole (5-D-3). These experimental results can be rationalized by a mechanism involving initial electrocyclic ring closure and sigmatropic shift of sulfur around the four sides of the azetine ring. Rearomatization of each bicyclic intermediate thus allows sulfur to insert into each position in the carbon-nitrogen sequence. As a consequence, these compounds divide into a tetrad in which isomers 1, 2,4, and 6 interconvert mainly via P5, P6, and P7 pathways and a dyad of two compounds in which 3 phototransposes to 5 via P5 and P7 pathways. Within the tetrad, BC-6, the bicyclic intermediate derived from 5-phenylisothiazoles (6), is postulated to undergo deuteration with simultaneous sigmatropic shift of sulfur when the reaction is carried out in benzene-D2O. This mechanistic view provides one coherent interpretation for the observed phototransposition and photodeuteration reactions.
- Pavlik, James W.,Tongcharoensirikul, Pakamas,Bird, Nigel P.,Day, A. Colin,Barltrop, John A.
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p. 2292 - 2300
(2007/10/02)
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- N-(4-Substituted-thiazolyl)oxamic Acid Derivatives, a New Series of Potent, Orally Actve Antiallergy Agents
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A series of N-(4-substituted-thiazolyl)oxamic acid derivatives were synthesized and tested for antiallergy activity in the rat PCA model.These compounds were conveniently prepared by treatment of the appropriate acetophenone with thiourea and iodine or by reaction of the chloroacetylbenzene with thiourea to give the corresponding aminothiazoles; subsequent condensation with ethyloxalyl chloride gave the thiazolyloxamates.Many of the analogues showed a 50percent inhibition at oxamic acid ethanolamine salt (61, PRH-836-EA), has been selected for further pharmacological evaluation.
- Hargrave, Karl D.,Hess, Friedrich K.,Oliver, James T.
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p. 1158 - 1163
(2007/10/02)
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