- Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility
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Following the approval of delamanid and pretomanid as new drugs to treat drug-resistant tuberculosis, there is now a renewed interest in bicyclic nitroimidazole scaffolds as a source of therapeutics against infectious diseases. We recently described a nitroimidazopyrazinone bicyclic subclass with promising antitubercular and antiparasitic activity, prompting additional efforts to generate analogs with improved solubility and enhanced potency. The key pendant aryl substituent was modified by (i) introducing polar functionality to the methylene linker, (ii) replacing the terminal phenyl group with less lipophilic heterocycles, or (iii) generating extended biaryl side chains. Improved antitubercular and antitrypanosomal activity was observed with the biaryl side chains, with most analogs achieved 2- to 175-fold higher activity than the monoaryl parent compounds, with encouraging improvements in solubility when pyridyl groups were incorporated. This study has contributed to understanding the existing structure-activity relationship (SAR) of the nitroimidazopyrazinone scaffold against a panel of disease-causing organisms to support future lead optimization.
- Ang, Chee Wei,Tan, Lendl,Sykes, Melissa L.,Abugharbiyeh, Neda,Debnath, Anjan,Reid, Janet C.,West, Nicholas P.,Avery, Vicky M.,Cooper, Matthew A.,Blaskovich, Mark A. T.
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p. 15726 - 15751
(2020/12/02)
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- REDUCTION OF PRO-INFLAMMATORY HDL USING A LEUKOTRIENE INHIBITOR
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A method involving the administration of a therapeutically effective amount of a leukotriene inhibitor, a pharmaceutically acceptable salt, a pharmaceutically acceptable N-oxide, a pharmaceutically active metabolite, a pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof to a human for reducing a level of pro-inflammatory HDL in the human. Various examples of leukotriene inhibitors, including 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin- 3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2, 2-dimethyl-propionic acid, are disclosed for administration for the reduction of pro-inflammatory HDL in a human. Reduction of pro-inflammatory HDL by the leukotriene inhibitor may include conversion of at least a portion of pro-inflammatory HDL to anti-inflammatory HDL.
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Paragraph 00204
(2018/09/12)
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- PHARMACEUTICAL COMPOSITION FOR TREATING OR PREVENTING GLAUCOMA
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The present invention is to provide a medical composition for the treatment or prophylaxis of glaucoma which comprises a pyridylaminoacetic acid compound represented by the formula (1): wherein R1, R2 and R3 each independe
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Page/Page column 103
(2012/02/15)
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- SUBSTITUTED CARBONYL COMPOUNDS
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This is to provide a novel substituted carbonyl compound represented by the following formula (I) having an excellent bronchodilatory action based on potent EP2 agonistic action and useful for treatment of respiratory diseases. A compound represented by t
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Page/Page column 23-24
(2012/07/28)
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- PYRIDYLAMINOACETIC ACID COMPOUND
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The present invention provides a novel pyridylaminoacetic acid compound represented by the following formula (1): (wherein R1, R2, R3, Y and Z are as defined in the description and claims), or a pharmacologically acceptabl
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Page/Page column 101
(2011/01/11)
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- 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
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Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.
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Page/Page column 64
(2008/06/13)
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- GLYCOPYRANOSYLOXYPYRAZOLE DERIVATIVES AND MEDICINAL USE THEREOF
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The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein one of Q and T represents a group represented by the general formula: while the other represents a lower alkyl group or a halo(lower alkyl) gr
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