484-94-6Relevant academic research and scientific papers
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Paragraph 0192, (2016/10/06)
The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Page/Page column 54, (2014/09/03)
The present invention provides compounds of Formula(I) or a pharmaceutically acceptable salt thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure, kidney disease, edema, and conditions associated with excessive salt and water retention.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Page/Page column 83, (2013/03/26)
The present invention provides compounds of Formula Ia and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.
Isothiazoloquinolones with enhanced antistaphylococcal activities against multidrug-resistant strains: Effects of structural modifications at the 6-, 7-, and 8-positions
Wang, Qiuping,Lucien, Edlaine,Hashimoto, Akihiro,Pais, Godwin C. G.,Nelson, David M.,Song, Yongsheng,Thanassi, Jane A.,Marlor, Christopher W.,Thoma, Christy L.,Cheng, Jijun,Podos, Steven D.,Ou, Yangsi,Deshpande, Milind,Pucci, Michael J.,Buechter, Douglas D.,Bradbury, Barton J.,Wiles, Jason A.
, p. 199 - 210 (2007/10/03)
We describe the biological evaluation of isothiazoloquinolones (ITQs) having structural modifications at the 6-, 7-, and 8-positions. Addition of a methoxy substituent to C-8 effected an increase in antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and a decrease in cytotoxic activity against Hep2 cells. Removal of fluorine from C-6 or replacement of the C-8 carbon with a nitrogen compromised anti-MRSA activity. When the groups attached at C-7 were compared, the anti-MRSA activity decreased in the order 6-isoquinolinyl > 4-pyridinyl > 5-dihydroisoindolyl > 6-tetrahydroisoquinolinyl. The compound with the most desirable in vitro biological profile was 9-cyclopropyl-6-fluoro-8-methoxy-7-(2-methylpyridin-4-yl) -9H-isothiazolo[5,4-b]quinoline-3,4-dione (7g). This ITQ demonstrated (i) strong in vitro anti-MRSA activity (MIC90 = 0.5 μg/mL), (ii) strong inhibitory activities against S. aureus DNA gyrase and topoisomerase IV, with weak activity against human topoisomerase II, (iii) weak cytotoxic activities against three cell lines, and (iv) efficacy in an in vivo murine thigh model of infection employing MRSA.
NEW ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS
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Page/Page column 51-53, (2008/06/13)
The invention provides certain compounds and salts of Formula I and Formula II:which possess antimicrobial activity. The invention also provides novel synthetic intermediatesuseful in making compounds of Formula I and Formula II. The variables A1, R2, R3, R5, R6, R7, A8, and Rg are defined herein. Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in animals.
ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS
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Page/Page column 54-55, (2010/02/11)
The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.
A novel method for the nitration of simple aromatic compounds
Smith, Keith,Musson, Adam,DeBoos, Gareth A.
, p. 8448 - 8454 (2007/10/03)
Simple aromatic compounds such as benzene, alkylbenzenes, halogenobenzenes, and some disubstituted benzenes are nitrated in excellent yields with high regioselectivity under mild conditions using zeolite β as a catalyst and a stoichiometric quantity of nitric acid and acetic anhydride. The zeolite can be recycled, and the only byproduct is acetic acid, which can be separated easily from the nitration product by distillation; the process is inexpensive and represents an attractive method for the clean synthesis of a range of nitroaromatic compounds. For example, nitration of toluene gives a quantitative yield of mononitrotoluenes, of which 79% is 4-nitrotoluene; fluorobenzene gives a quantitative yield of mononitro compounds, of which 94% is 4-nitrofluorobenzene; and 2-fluorotoluene gives a 96% yield of mononitro products, of which 90% is the 5-nitro isomer and 10% is the 4-nitro isomer.
A Novel Electrophilic Fluorination of Activated Aromatic Rings Using Acetyl Hypofluorite, Suitable also for Introducing (18)F into Benzene Nuclei
Lerman, Ori,Yitzhak, Tor,Hebel, David,Rozen, Shlomo
, p. 806 - 813 (2007/10/02)
Acetyl hypofluorite (1) is a new compound that serves as a novel electrophilic fluorinating agent.It is special in the sense that, while it is very reactive, it is still a milder reagent than other fluoroxy compounds such as CF3OF or CF3COOF.It is synthesized directly from elemental fluorine and is used without any isolation or purification.The hypofluorite 1 reacts efficiently and selectively with activated aromatic rings,particularly phenol and aniline derivatives after suitable protection of the hydroxyl and the amino groups.The net result of the reaction is partly according to classical aromatic electrophilic substitution.Unlike such a substitution, however, the electrophilic fluorine atom of 1 substitutes mainly an ortho hydrogen and only occasionally small amounts of p-fluoro derivatives are found.Evidence supports the mechanism for this aromatic fluorination as being mainly an addition-elimination one.In many cases the electrophilic aromatic fluorinations can replace the classical 60-year-old Balz-Schiemann method, which until today is probably the most used procedure.Since aromatic fluorination with 1 is a very fast reaction and since 1 is produced directly from elemental fluorine, this is probably one of the best ways for introduction of the short-living radioisotope (18)F into activated aromatic rings.This will greatly encourage the synthesis of compounds suitable for use in the rapidly developing field of positron emitting transaxial tomography, which in itself depends on the efficient and easy supply of compounds possessing positron emitting isotopes.
Etude des complexes du cobalt (II) transporteurs d'oxygene: Nouvelle synthese du fluoro-3 hydroxy-2 benzaldehyde
Aymes, Daniel J.,Paris, Michel R.
, p. 175 - 178 (2007/10/02)
Synthetic chelates of cobalt (II) derived from Schiff bases have remarkable behavior of reversibly absorbing and releasing molecular oxygene.Among these, bis (3-fluorosalicylaldehydeethylenediimide) Co (II) (fluomine: Formula A, X=F) is most interesting in allowing to isolate pure oxygen from air, because it absorbs with extreme rapidity 4.43percent of its weight of oxygen.Fluomine is easily prepared from 3-fluorosalicylaldehyde (3FSA), ethylenediamine and cobalt (II) chloride; but substances such as 3-substituted salicylaldehydes have proven to be extremely difficult to prepare in other than small laboratory quantities from the corresponding ortho-substituted phenol.Many author have prepared 3-fluorosalicylaldehyde, as described in patents, but often these syntheses are very long and the yields are generally less than 20percent.We now describe a new synthesis from o-fluorophenol.Nitration of o-fluorophenol with liquid nitrogen dioxide is convenient: - on the one hand, ortho-substitution to the hydroxyl group, is easy, -on the other hand, the para substituted by-product, is reinserted in the course of the synthesis, so that it is possible to minimize loss of the starting phenol, an expensive product. o-Fluorophenol 1 in solution in pentane, at about 0 deg C, is treated with liquid nitrogen dioxide (slight excess).The reaction is rapid and leads to 2-fluoro 6-nitrophenol 2 which remains in solution, and 2-fluoro 4-nitrophenol 7 which cristallizes rapidly (approximatively 50percent of each one). 2-Fluoro 6-nitrophenol 2 is converted into the anisole 3, the NO2 group of which is catalytically reduced by hydrogen into 3-fluoro 2-methoxy-aminobenzene 4.This amine 4 is diazotized, and treated with formaldoxime to lead to 3-fluoro 2-methoxybenzaldehyde 5 (Eb12 = 82 deg C). 3FSA is finally obtained by heating under reflux anisole 5 and a solution of hydrobromic acid (48percent). 2-Fluoro 4-nitrophenol 7 is converted in five steps into 3-fluoro 2-methoxyaminobenzene 4 by the same reactions as these used for its isomer.Finally the total yield of amine 4 from o-fluorophenol is 73percent, and 3FSA is obtained in 25percent yield.No primary amines are required during the isolation, so that no possible contamination of the final product is possible and therefore the fluomine prepared therefrom is not contaminated and deactivated.
