- Discovery of new hit-molecules targeting Plasmodium falciparum through a global SAR study of the 4-substituted-2-trichloromethylquinazoline antiplasmodial scaffold
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From 4 antiplasmodial hit-molecules identified in 2-trichloromethylquinazoline series, we conducted a global Structure-Activity relationship (SAR) study involving 26 compounds and covering 5 molecular regions (I – V), aiming at defining the corresponding
- Desroches, Justine,Kieffer, Charline,Primas, Nicolas,Hutter, Sébastien,Gellis, Armand,El-Kashef, Hussein,Rathelot, Pascal,Verhaeghe, Pierre,Azas, Nadine,Vanelle, Patrice
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Read Online
- Chemical Space Exploration around Thieno[3,2- d]pyrimidin-4(3 H)-one Scaffold Led to a Novel Class of Highly Active Clostridium difficile Inhibitors
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Clostridium difficile infection (CDI) is the leading cause of healthcare-associated infection in the United States. Therefore, development of novel treatments for CDI is a high priority. Toward this goal, we began in vitro screening of a structurally diverse in-house library of 67 compounds against two pathogenic C. difficile strains (ATCC BAA 1870 and ATCC 43255), which yielded a hit compound, 2-methyl-8-nitroquinazolin-4(3H)-one (2) with moderate potency (MIC = 312/156 μM). Optimization of 2 gave lead compound 6a (2-methyl-7-nitrothieno[3,2-d]pyrimidin-4(3H)-one) with improved potency (MIC = 19/38 μM), selectivity over normal gut microflora, CC50s > 606 μM against mammalian cell lines, and acceptable stability in simulated gastric and intestinal fluid. Further optimization of 6a at C2-, N3-, C4-, and C7-positions resulted in a library of >50 compounds with MICs ranging from 3 to 800 μM against clinical isolates of C. difficile. Compound 8f (MIC = 3/6 μM) was identified as a promising lead for further optimization.
- Shao, Xuwei,Abdelkhalek, Ahmed,Abutaleb, Nader S.,Velagapudi, Uday Kiran,Yoganathan, Sabesan,Seleem, Mohamed N.,Talele, Tanaji T.
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p. 9772 - 9791
(2019/11/03)
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- Thienopyrimidine derivative as an active ingredient a plant disease control agent (by machine translation)
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[Problem] in plant disease resistance-inducing gene expression found thienopyrimidine derivative effect, utilizing the thienopyrimidine derivatives, injuries to plant disease organisms[Solution] some of the thienopyrimidine derivatives, such as gene expression in a plant disease-resistance gene to induce PR-a 1, therefore cruciferous vegetables against plant diseases caused by pathogenic bacillus anthracis, exhibiting excellent control effect was found. [Drawing] no (by machine translation)
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- MONOCYCLIC, THIENO, PYRIDO, AND PYRROLO PYRIMIDINE COMPOUNDS AND METHODS OF USE AND MANUFACTURE OF THE SAME
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The present invention provides monocyclic, thieno, pyrido and pyrrolo pyrimidine compounds. Pharmaceutical compositions comprising one or more of these compounds and optionally comprising a pharmaceutically acceptable salt or hydrate of one or more of the compounds are provided. Preferably, these pharmaceutical compositions further comprise at least one pharmaceutically acceptable carrier. Methods of treating a patient having cancer are provided wherein a therapeutically effective amount of one or more of these compounds or pharmaceutical compositions are administered to the patient.
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Page/Page column 97-98
(2017/03/21)
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- THIENO[3,2-D]PYRIMIDINE-6-CARBOXAMIDES AND ANALOGUES AS SIRTUIN MODULATORS
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Provided herein are novel substituted thieno[3,2-d]pyrimidine-6-carboxamide sirtuin inhibitors and methods of use thereof. The sirtuin inhibitors may be used for inhibiting a sirtuin-mediated biological process, and, e.g. for treating and/or preventing diseases and disorders including, but not limited to cancer, neurodegenerative disease and inflammation. Also provided herein are pharmaceutical compositions comprising these sirtuin inhibitors and compositions comprising a sirtuin inhibitor in combination with another therapeutic agent.
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- Microwave-assisted synthesis of potent PDE7 inhibitors containing a thienopyrimidin-4-amine scaffold
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A series of novel thienopyrimidin-4-amines have been synthesized and evaluated as phosphodiesterase (PDE) inhibitors. A rationale for the observed selectivity against PDE7 has been obtained from molecular modelling studies on the most active compounds. This journal is the Partner Organisations 2014.
- Sanchez, Ana I.,Meneses, Ricardo,Minguez, Jose M.,Nunez, Araceli,Castillo, Rafael R.,Filace, Fabiana,Burgos, Carolina,Vaquero, Juan J.,Alvarez-Builla, Julio,Cortes-Cabrera, Alvaro,Gago, Federico,Terricabras, Emma,Segarra, Victor
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supporting information
p. 4233 - 4242
(2014/06/10)
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- NEW COMPOUNDS
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There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.
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Page/Page column 82-83
(2012/12/13)
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- Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives
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The (-)-(11R,2′S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A2A receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and selective antagonists of the adenosine A2A receptor. These derivatives show selectivity against the A1 receptor. Furthermore, some of these compounds have been shown to have in vivo activity in a commonly used model, suggesting the potential for the treatment of Parkinson's disease.
- Gillespie, Roger J.,Adams, David R.,Bebbington, David,Benwell, Karen,Cliffe, Ian A.,Dawson, Claire E.,Dourish, Colin T.,Fletcher, Allan,Gaur, Suneel,Giles, Paul R.,Jordan, Allan M.,Knight, Antony R.,Knutsen, Lars J.S.,Lawrence, Anthony,Lerpiniere, Joanne,Misra, Anil,Porter, Richard H.P.,Pratt, Robert M.,Shepherd, Robin,Upton, Rebecca,Ward, Simon E.,Weiss, Scott M.,Williamson, Douglas S.
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p. 2916 - 2919
(2008/12/22)
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- N-aryl-thienopyrimidin-4-amines and analogs as activators of caspases and inducers of apoptosis and the use thereof
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Disclosed are N-aryl-thienopyrimidin-4-amines and analogs thereof, represented by the Formulae I-II: wherein Ar and R1-R4 are defined herein. The present invention relates to the discovery that compounds having Formulae I-II are acti
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Page/Page column 9; 23-24
(2008/06/13)
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- N-ALKYL-N-ARYL-THIENOPYRIMIDIN-4-AMINES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
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Disclosed are N-alkyl-N-aryl-thienopyrimidin-4-amines and analogs thereof, represented by the Formulae I-II: wherein Ar, R1 -R4 and R10 are defined herein. The present invention relates to the discovery that compounds havi
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Page/Page column 33
(2008/06/13)
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