- NOVEL PHENICOL ANTIBACTERIAL AGENTS
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The present invention provides novel phenicol derivatives, their use for the treatment of infections in mammals, pharmaceutical compositions containing these novel compounds, and methods for the preparation of these compounds.
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Page/Page column 21
(2014/11/11)
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- PHENICOL ANTIBACTERIALS
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The present invention provides novel phenicol derivatives, their use for the treatment of infections in mammals, pharmaceutical composition containing these novel compounds, and methods for the preparation of these compounds.
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Paragraph 0323
(2013/09/26)
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- Dynamics of closure of zinc bis-porphyrin molecular tweezers with copper(II) ions and electron transfer
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Zinc bis-porphyrin molecular tweezers composed of a N4 spacer bound through pyridyl units to the meso position of porphyrins were synthesized, and the tweezers are closed by the coordination of a copper(II) ion inside the spacer ligand. The effect of the π-π interaction between the porphyrin rings in the closed conformation on the absorption spectra of multi-electron oxidized species and the reduction potentials were clarified by chemical and electrochemical oxidation of the closed form of the zinc bis-porphyrin molecular tweezers in comparison with the open form without copper(II) ion and the corresponding porphyrin monomer. The shifts in redox potentials and absorption spectrum of the porphyrin dication indicate a strong electronic interaction between the two oxidized porphyrins in the closed form, whereas there is little interaction between them in the neutral form. The dynamics of copper(II) ion coordination and subsequent electron transfer was examined by using a stopped-flow UV/Vis spectroscopic technique. It was confirmed that coordination of copper(II) occurs prior to electron-transfer oxidation of the closed form of the zinc bis-porphyrin molecular tweezers.
- Habermeyer, Benoit,Takai, Atsuro,Gros, Claude P.,El Ojaimi, Maya,Barbe, Jean-Michel,Fukuzumi, Shunichi
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p. 10670 - 10681
(2011/11/06)
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- Inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies
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1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.
- Deng, Lisheng,Diao, Jiasheng,Chen, Pinhong,Pujari, Venugopal,Yao, Yuan,Cheng, Gang,Crick, Dean C.,Prasad, B. V. Venkataram,Song, Yongcheng
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p. 4721 - 4734
(2011/09/19)
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- NITROIMIDAZOOXAZINES AND THEIR USES IN ANTI-TUBERCULAR THERAPY
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The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.
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Page/Page column 29
(2011/02/24)
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- Towards the synthesis of substituted porphyrins by a pyridyl group bearing a reactive functionality
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Pyridyl-substituted porphyrins bearing a reactive functionality were prepared via Suzuki cross-coupling reactions and resulted in very good yields. These compounds are precursors of new porphyrin architectures able to coordinate two metals: one in the porphyrin core and the second around the pyridyl moiety. During the coupling reactions, a higher reactivity of a chloro picolyl group was evidenced compared to a bromo function on the same reacting molecule.
- Ojaimi, Maya El,Habermeyer, Benoit,Gros, Claude P.,Barbe, Jean-Michel
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p. 469 - 480
(2011/03/20)
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- Synthesis and structure-activity relationships of aza- and diazabiphenyl analogues of the antitubercular drug (6 S)-2-nitro-6-{[4-(trifluoromethoxy) benzyl]oxy}-6,7-dihydro-5 H-imidazo[2,1-b][1,3]oxazine (PA-824)
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New heterocyclic analogues of the potent biphenyl class derived from antitubercular drug PA-824 were prepared, aiming to improve aqueous solubility but maintain high metabolic stability and efficacy. The strategy involved replacement of one or both phenyl
- Kmentova, Iveta,Sutherland, Hamish S.,Palmer, Brian D.,Blaser, Adrian,Franzblau, Scott G.,Wan, Baojie,Wang, Yuehong,Ma, Zhenkun,Denny, William A.,Thompson, Andrew M.
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body text
p. 8421 - 8439
(2011/02/21)
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- Synthesis of diethyl{[5-(3-fluorophenyl)-pyridine-2yl]methyl}phosphonate
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This application discloses a novel process for the preparation of phosphonate esters useful as intermediates in the preparation of himbacine analogs, themselves useful as thrombin receptor antagonists. The chemistry taught herein can be exemplified by the following scheme: wherein R9 is selected from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms, and R11 is selected independently for each occurrence from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms and hydrogen, X2 is Cl, Br, or I; X3 is selected from Cl and Br; and PdLn is a supported palladium metal catalyst or a soluble heterogeneous palladium catalyst. The L-derivatizing reagent is a moiety which converts the alcohol functional group of compound 137D to any leaving group which can be displaced by a triorgano-phosphite phosphonating agent.
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Page/Page column 13-14
(2008/06/13)
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- HYDANTOIN DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISORDERS
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This invention relates to compounds of the Formula: (I); or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, aggrecanase, TNF-α or combinations thereof.
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- EXO- AND DIASTEREO- SELECTIVE SYNTHESES OF HIMBACINE ANALOGS
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The application discloses a novel process for the preparation of himbacine analogs useful as thrombin receptor antagonists. The process is based in part on the use of a base-promoted dynamic epimerization of a chiral nitro center. The chemistry taught her
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Page/Page column 46
(2008/06/13)
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- Synthesis of a Non-Heme Template for Attaching Four Peptides: An Approach to Artificial Iron (II)-Containing Peroxidases
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We are developing all-synthetic model cofactor-protein complexes in order to define the parameters controlling non-natural cofactor activity. The long-term objective is to establish the theoretical and practical basis for designing novel enzymes. A non-heme pentadentate ligand (N4Py) is being developed as a template for the site-specific attachment of a designed four-helix bundle. Previously, we attached two unprotected peptides via CH 2Cl handles to N4Py. In the presence of hydrogen peroxide, the iron(II) complex of this ligand (2a) generates an FeIIIOOH intermediate (3a) that can oxidize a wide variety of organic compounds. Here, we describe the synthesis of 27, a N4Py derivative in which four three-carbon spacers have been introduced, and show that four copies of an unprotected, single-cysteine peptide can be coupled via a thioether linkage to the ligand. In addition, a divergent synthesis route to tetrabromide ligand lb has also been developed, providing the opportunity to prepare alternative pentadentate ligands efficiently by four cross-coupling reactions on a single molecule. Also, two of the four bromides of lb can be selectively addressed by magnesium-bromide exchange.
- Van Den Heuvel, Marco,Van Den Berg, Tieme A.,Kellogg, Richard M.,Choma, Christin T.,Feringa, Ben L.
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p. 250 - 262
(2007/10/03)
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