- Development of inhibitors against mycobacterium abscessus tRNA (m1G37) Methyltransferase (TrmD) Using Fragment-Based Approaches
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Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in accelerated lung function decline and premature death. There is therefore an urgent need to develop novel antibiotics with improved efficacy. tRNA (m1G37) methyltransferase (TrmD) is a promising target for novel antibiotics. It is essential in Mab and other mycobacteria, improving reading frame maintenance on the ribosome to prevent frameshift errors. In this work, a fragment-based approach was employed with the merging of two fragments bound to the active site, followed by structure-guided elaboration to design potent nanomolar inhibitors against Mab TrmD. Several of these compounds exhibit promising activity against mycobacterial species, including Mycobacterium tuberculosis and Mycobacterium leprae in addition to Mab, supporting the use of TrmD as a target for the development of antimycobacterial compounds.
- Whitehouse, Andrew J.,Thomas, Sherine E.,Brown, Karen P.,Fanourakis, Alexander,Chan, Daniel S.-H.,Libardo, M. Daben J.,Mendes, Vitor,Boshoff, Helena I. M.,Floto, R. Andres,Abell, Chris,Blundell, Tom L.,Coyne, Anthony G.
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supporting information
p. 7210 - 7232
(2019/08/20)
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- Highly hydrophobic isoreticular porous metal-organic frameworks for the capture of harmful volatile organic compounds
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Tunable hydrophobicity: Efficient air filters for the protection against chemical warfare agents might be achieved by surface functionalization of the pores in robust metal-organic frameworks (MOFs) with fluoroalkyl residues and the precise control of their pore size (see picture). These MOFs capture harmful volatile organic compounds even under extremely moist conditions (80 % relative humidity). Copyright
- Padial, Natalia M.,Quartapelle Procopio, Elsa,Montoro, Carmen,Lopez, Elena,Oltra, J. Enrique,Colombo, Valentina,Maspero, Angelo,Masciocchi, Norberto,Galli, Simona,Senkovska, Irena,Kaskel, Stefan,Barea, Elisa,Navarro, Jorge A. R.
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supporting information
p. 8290 - 8294
(2013/09/02)
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- AMIDE COMPOUNDS AND MEDICINAL USE THEREOF
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The present invention relates to a compound of the formula wherein R1 is substituted aryl, heteroaryl and the like, R2 and R3 are hydrogen, alkyl, halogen, hydroxyl group and the like, Q is N, CH and the like, W is hydrogen, alkyl, hydroxycarbonylalkyl and the like, X is halogen, cyano, nitro, amino and the like, X' is hydrogen, halogen, cyano, nitro, and Y is alkyl, hydroxyl group, alkoxy, mercapto and the like and a salt thereof, and a medicine containing the said compound. The compound of the present invention shows a superior inhibitory effect on activated lymphocytes proliferation and is useful as an agent for the prophylaxis or treatment of various autoimmune diseases.
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- Metallacarborane chelates
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Metallacarborane chelate-antibody compounds which are useful for radioimmunodetection and radiotherapy. The compounds have the formula STR1 wherein X is a metal or radioisotope of said metal, Y is a rotation resistant organic chelate bridge moiety, Z is an antibody linkage moiety and AB is an antibody. Metallacarborane chelate and carborane chelate compounds are also disclosed which are useful in preparing the final metallacarborane chelate-antibody compound which is used for radioimmunodetection and radiotherapy.
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- Pyridazines. XXIII . A Novel Pyridazine into Pyrazole Ring Transformation
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Treatment of phenyl(4-pyridazinyl)methanols 1a and 1b with p-toluenesulfonic acid at elevated temperatures causes transformation into the C-4 substituted pyrazole derivatives 8a and 8b.Limitations of this novel rearrangement reaction as well as mechanistic considerations are discussed.Furthemore, the preparation of hitherto unknown 4-pyridazinylmethanols 1b, 3, and 7 is described.
- Heinisch, Gottfried,Waglechner, Richard
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p. 1727 - 1731
(2007/10/02)
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