WO2009010163A1 - New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections - Google Patents
New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections Download PDFInfo
- Publication number
- WO2009010163A1 WO2009010163A1 PCT/EP2008/005142 EP2008005142W WO2009010163A1 WO 2009010163 A1 WO2009010163 A1 WO 2009010163A1 EP 2008005142 W EP2008005142 W EP 2008005142W WO 2009010163 A1 WO2009010163 A1 WO 2009010163A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- linear
- branched aliphatic
- chain members
- formula
- unsaturated
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/04—1,3-Thiazines; Hydrogenated 1,3-thiazines
- C07D279/08—1,3-Thiazines; Hydrogenated 1,3-thiazines condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
Definitions
- New antimicrobial compounds their synthesis and their use for treatment of mammalian infections
- the present invention relates to novel benzothiazin derivatives and their use as antibacterial agents in infectious diseases of mammals (humans and animals) caused by bacteria, especially diseases like tuberculosis (TB) and leprosy caused by mycobacteria.
- mycobacteria resistant at least against two of the most active tuberculosis drugs, isoniazid and rifampicin, but also against streptomycin, pyranzinamid and ethambutol.
- the proportion of MDR-TB in some countries is already more than 20%. Even more threatening became the situation since the first cases of XDR-TB (extremly resistant TB) were diagnosed last year in South Africa. Now XDR-TB is already spread over all continents.
- Mycobacteria causing XDR-TB are resistant against the first line TB drugs Rifampicin, Isoniazid, Pyrazinamid, Ethambutol and additionally against the second line chinolones and aminoglycosides. (Nature Med. 2007,13, 295-298) Together with the increased number of TB diseases generally, worldwide it causes about 2.000.000 deaths annually.
- the present invention aims at the generation of new compounds with activity against mycobacteria as potential new tuberculosis drugs to overcome problems concerning resistance and drug intolerance.
- R 1 and R 2 are, independently of each other, NO 2 , NR 7 R 8 , NHOR 9 , COOR 9 , CN, CONR 10 R 11 , CHO, F, Cl, Br, SO 2 NR 12 R 13 , lower alkoxy, OCF 3 , mono-, di or trifluoromethyl;
- R 3 and R 4 are, independently of each other, H, a saturated or unsaturated, linear or branched aliphatic radical having 1-3 chain members, F, Cl, Br, lower alkoxy;
- R 5 is H, a saturated or unsaturated, halogenated or unhalogenated, linear or branched aliphatic radical having 1 -7 chain members;
- R 6 is a radical:
- X is saturated or unsaturated, halogenated or unhalogenated, linear or branched aliphatic radical having 1-5 chain members, or
- R 5 and R 6 together represent bivalent radicals wherein n is 1-4:
- R - R are, independently of each other H or a saturated or unsaturated, halogenated or unhalogenated, linear or branched aliphatic radical having 1-5 chain members, phenyl, benzyl or R 7 and R 8 together, R 10 and R 11 together, R 12 and R 13 together represent a linear or branched aliphatic bivalent radical having 1-7 chain members;
- R 14 and R 15 are, independently of each other, H, linear or branched aliphatic radical having 1-5 chain members, F, Cl, Br, NO 2 , NH 2 , CF 3 .
- the invention concerns compounds of the formula (I) selected from the group consisting of
- Methods A, B and C propose to use as starting material well known polysubstituted 2-chloro(bromo)- benzcarboxamides, many of them described in the literature or can be easily prepared by analogues methods (Isaew S. G. Farm. Zh. (Kiev), 2000, 52; Makosza M., Nizamov S. Org. Prep, and Proced. Int., 1997, 29, 707; Nerin C, Tornes A. R., Domento C, Cacho J. J. Agr.
- the starting 2-chlorobenzcarboxamides were treated by 1,0-1,2 equimolar quantity of the metal salts of dithiocarbamates in alcohols, aceton or in their mixture under 0-50 0 C for a period of about one quater of an hour to about 24 hours.
- this reaction is conducted in alcohol at room temperature.
- the reaction mixture was diluted by water and solid 2-dithiocarbamoylbenzcarboxamide was filtered off.
- 2-Dithiocarbamoylbenzcarboxamide was treated by light alkaly (e.g.
- This method proposes to use excess of metal dithiocarbamate as light alkaly in the benzothiazinone cyclization and not to isolate 2- dithiocarbamoylbenzcarboxamide.
- the starting 2- chlorobenzcarboxamides can be treated with a 1,2-2,5 equimolar quantity of the metal salts of dithiocarbamates in alcohols, aceton or in their mixture at 20-80 0 C for a period of about 3-36 hours.
- this reaction is conducted in alcohol or in a mixture of water/alcohol at 50-75 0 C for about 24 hours.
- the aimed 2-substituted-4H-l,3- benzothiazin-4-one is obtained by recovery procedures from method A.
- This method uses as starting material 2-chlorobenzencarboxamides. These compounds were treated with 1,1-2,0 fold excess of metal salts of alkylxantogenate, for example commercial available potassium ethylxantogenate, at a temperature of 20-100 0 C in different alcohols, acetone, acetonitrile or other suitable organic solvents for a period of about one half hour to about 24 hours. Preferably, this reaction is conducted in alcohol at room temperature for about 24 hours.
- alkylxantogenate for example commercial available potassium ethylxantogenate
- the isolated 2-alkoxy-4/- 7" -l,3-benzothiazin-4-one was treated with the corresponding amine HNR 5 R 6 in acetic acid, alcohols, ethylacetate, DMF, aceton or acetonitril for a period of up to 48 hours for full exchange of the alkoxy group to the corresponding amine.
- the reaction mixture can be evaporated and diluted by water or it can be diluted by water directly.
- the aimed 2- NR 5 R 6 -477- l,3-benzothiazin-4-one is recovered by customary isolation procedures, e.g. filtration and recrystallization from a suitable organic solvent.
- the compounds of the invention exhibit strong antibacterial activity, especially against mycobacteria with minimal inhibitory concentrations (MIC) in the range of 0,000012 - 0,78 ⁇ g/ml for fast growing mycobacteria, of ⁇ 0.39 - 3.12 ⁇ g/ml for M. tuberculosis, including multiresistant strains, determined by the classical method and of 2.0 - 50.0 ng/ml for M. tuberculosis H37Rv determined by the Alamar Blue method.
- the compounds of the invention demonstrate a high level of selectivity for mycobacteria only which reduces the potential for adverse side effects dramatically.
- the compounds of the invention are non-mutagenic at 5 mg/ml in the SOS chromotest (M.Isidori, M. Lavorgna, A.Nardelli, L.Pascarella, A. Parella, Sd. Total Environ., 2005, 346, 87-98; M. Bombardier, N. Bermingham, R. Legault, A. Fouquet, Chemosphere, 2001, 42, 931-44; D.A. Widdick, D.I. Edwards, Mutat. Res., 1991, 259, 89-93).
- the compounds of the invention are useful for the treatment of tuberculosis infections and other mycobacterial infections, in humans and in animals.
- the invention concerns pharmaceutical compositions comprising a compound of the formula I.
- the invention relates furthermore to a compound of the formula I for use in a method for the treatment of bacterial infections in mammals.
- Preferred compounds of the formula I for use in such method are those specifically listed above.
- the compounds of the invention are formulated for use by preparing a diluted solution or suspension in pharmaceutically acceptable aqueous, organic or aqueous-organic medium for topical or parenteral administration by intravenous, subcutaneous or intramuscular injection, or for intranasal application; or are prepared in tablet, capsule or aqueous suspension form with conventional excipients for oral administration or as suppositorium.
- the compounds can be used in dosages from 0.001 - 1000 mg/kg body weight.
- the structures of the compounds of the invention were established by modes of synthesis and elementary analysis, and by nuclear magnetic resonance and mass spectra.
- Example 7 2-(4-Benzylpiperazin- 1 -y ⁇ - ⁇ -nitro- ⁇ - ⁇ rifluoromethyl) ⁇ //- 1 ,3-benzo- thiazin-4-one, (compound 7) Following the procedure of Example 4. Yellow crystalline solid. Yield 51%. mp 161-163 0 C (EtOH/DMF). MS m/z 450 (M + ).
- MBC minimal bactericidal concentration of drugs
- MIC bacteriostatic effect
- HSRE multiresistant strain
- XTB extremly resistant strain
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AP2010005131A AP2010005131A0 (en) | 2007-07-16 | 2008-06-25 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
EA201070145A EA017806B1 (en) | 2007-07-16 | 2008-06-25 | Antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
CA2693088A CA2693088C (en) | 2007-07-16 | 2008-06-25 | Antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
JP2010516390A JP5502731B2 (en) | 2007-07-16 | 2008-06-25 | New antimicrobial compounds, their synthesis and their use for the treatment of mammalian infections |
AT08773648T ATE482939T1 (en) | 2007-07-16 | 2008-06-25 | NEW ANTIMICROBIAL COMPOUNDS, THEIR SYNTHESIS AND THEIR USE FOR THE TREATMENT OF MAMMAL INFECTIONS |
AU2008278056A AU2008278056B2 (en) | 2007-07-16 | 2008-06-25 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
BRPI0813828-1A2A BRPI0813828A2 (en) | 2007-07-16 | 2008-06-25 | ANTIMICROBIAN COMPOUNDS, SUMMARY OF THE SAME AND THE USE OF THE SAME FOR THE TREATMENT OF INFECTIONS IN MAMMALS |
EP08773648A EP2176248B1 (en) | 2007-07-16 | 2008-06-25 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
MX2010000672A MX2010000672A (en) | 2007-07-16 | 2008-06-25 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections. |
DE602008002843T DE602008002843D1 (en) | 2007-07-16 | 2008-06-25 | NEW ANTIMICROBIAL COMPOUNDS, THEIR SYNTHESIS AND THEIR USE FOR THE TREATMENT OF MAMMALIAN INFECTIONS |
NZ582620A NZ582620A (en) | 2007-07-16 | 2008-06-25 | Benzothiazinone derivatives, their synthesis and their use for treatment of mammalian infections |
CN2008800248917A CN101809009B (en) | 2007-07-16 | 2008-06-25 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
US12/669,748 US8440842B2 (en) | 2007-07-16 | 2008-06-25 | Antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
TNP2010000023A TN2010000023A1 (en) | 2007-07-16 | 2010-01-13 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
EC2010009962A ECSP109962A (en) | 2007-07-16 | 2010-02-12 | NEW ANTIMICROBIAL COMPOUNDS, THEIR SYNTHESIS AND THEIR USE FOR THE TREATMENT OF INFECTIONS IN MAMMALS |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07013899A EP2020406A1 (en) | 2007-07-16 | 2007-07-16 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infection |
EP07013899.5 | 2007-07-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2009010163A1 true WO2009010163A1 (en) | 2009-01-22 |
Family
ID=38777913
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2008/005142 WO2009010163A1 (en) | 2007-07-16 | 2008-06-25 | New antimicrobial compounds, their synthesis and their use for treatment of mammalian infections |
Country Status (23)
Country | Link |
---|---|
US (1) | US8440842B2 (en) |
EP (2) | EP2020406A1 (en) |
JP (1) | JP5502731B2 (en) |
KR (1) | KR101588064B1 (en) |
CN (1) | CN101809009B (en) |
AP (1) | AP2010005131A0 (en) |
AT (1) | ATE482939T1 (en) |
AU (1) | AU2008278056B2 (en) |
BR (1) | BRPI0813828A2 (en) |
CA (1) | CA2693088C (en) |
CO (1) | CO6321160A2 (en) |
CR (1) | CR11240A (en) |
DE (1) | DE602008002843D1 (en) |
EA (1) | EA017806B1 (en) |
EC (1) | ECSP109962A (en) |
MA (1) | MA31607B1 (en) |
MX (1) | MX2010000672A (en) |
NI (1) | NI201000012A (en) |
NZ (1) | NZ582620A (en) |
TN (1) | TN2010000023A1 (en) |
UA (1) | UA99300C2 (en) |
WO (1) | WO2009010163A1 (en) |
ZA (1) | ZA201000491B (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2380886A1 (en) | 2010-04-23 | 2011-10-26 | Vadim A. Makarov | Process for the preparation of 2-aminosubstituted 1,3-benzothiazine-4-ones |
WO2012066518A1 (en) | 2010-11-19 | 2012-05-24 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
EP2468746A1 (en) | 2010-12-23 | 2012-06-27 | The University of Queensland | Benzothiazinone compounds and their use as anti-tuberculosis agents |
EP2570413A1 (en) | 2011-09-15 | 2013-03-20 | The University Of Queensland | Benzothiazinone derivatives as anti-tuberculosis agents |
US20150353572A1 (en) * | 2014-06-09 | 2015-12-10 | University Of Notre Dame Du Lac | 1,3-benzothiazinone, sulfoxide, and sulfone compounds with electrophilic substituent |
DE102014012546A1 (en) * | 2014-09-26 | 2016-03-31 | Martin-Luther-Universität Halle-Wittenberg | Antimycobacterially active substances, process for their preparation and their use |
EP3072889A1 (en) | 2015-03-23 | 2016-09-28 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-Homopiperazine-1-yl-4H-1,3-benzothiazine-4-one derivatives and process for the preparation of 2-(homo)piperazine 1,3-benzothiazine-4-one hydrochlorides |
WO2018055048A1 (en) | 2016-09-22 | 2018-03-29 | Leibniz-Institut Für Naturstoff-Forschung Und Infektionsbiologie E.V. Hans-Knöll Institut (Hki) | New antimicrobial compounds, their use for the treatment of mammalian infections and a new metabolic mechanism |
Families Citing this family (11)
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CN102276598B (en) * | 2011-05-27 | 2014-11-05 | 四川大学 | Benzothiazine-thione derivatives, preparation method thereof and purpose thereof |
CN103508980B (en) * | 2012-06-14 | 2016-07-06 | 四川大学 | Benzothiazine-4-ketone derivatives and its production and use |
CN112007622B (en) | 2015-07-27 | 2023-01-10 | 第六波创新公司 | Molecularly imprinted polymer beads for metal extraction and uses thereof |
CN105294597B (en) * | 2015-11-03 | 2017-11-24 | 华东师范大学 | Benzothiazine derivatives and its synthetic method and application |
CA3042533A1 (en) | 2016-11-03 | 2018-05-11 | 6th Wave Innovations Corp. | Molecularly imprinted polymer beads for extraction of lithium, mercury, and scandium |
CN108947952B (en) * | 2017-05-24 | 2021-09-21 | 中国医学科学院药物研究所 | 2-substituted amino-5-trifluoromethyl-8-nitrobenz (thio) pyran-4-ketone compound and preparation method and application thereof |
CN108929329B (en) * | 2017-05-24 | 2020-12-11 | 中国医学科学院药物研究所 | 2-azacyclo-5-trifluoromethyl-8-nitrobenz (thio) pyran-4-ones |
CN111303075A (en) * | 2020-04-08 | 2020-06-19 | 苏州大学 | Benzothiazinone derivative, preparation method thereof and application of benzothiazinone derivative as antituberculosis drug |
CN111269197A (en) * | 2020-04-08 | 2020-06-12 | 苏州大学 | Benzothiazinone compound, preparation method thereof and application of compound as antituberculosis drug |
US20240254116A1 (en) * | 2021-03-29 | 2024-08-01 | Soochow University | Benzothiazinone derivative substituted with trifluoromethyl at 6-position, and preparation method therefor and use thereof |
WO2023065182A1 (en) * | 2021-10-20 | 2023-04-27 | 苏州大学 | Benzothiazinone derivative based on alkynyl linking arm, preparation method therefor, and use thereof |
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US3522247A (en) * | 1967-11-07 | 1970-07-28 | Pfizer & Co C | 2-amino-6,7-disubstituted-4h-1,3-benzothiazine-4-ones as bronchodilators |
EP1568697A1 (en) * | 2002-12-05 | 2005-08-31 | Takeda Pharmaceutical Company Limited | 1,3-benzothiazinone derivatives, process for producing the same and use thereof |
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Family Cites Families (1)
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-
2007
- 2007-07-16 EP EP07013899A patent/EP2020406A1/en not_active Withdrawn
-
2008
- 2008-06-25 US US12/669,748 patent/US8440842B2/en active Active
- 2008-06-25 NZ NZ582620A patent/NZ582620A/en not_active IP Right Cessation
- 2008-06-25 BR BRPI0813828-1A2A patent/BRPI0813828A2/en not_active IP Right Cessation
- 2008-06-25 JP JP2010516390A patent/JP5502731B2/en active Active
- 2008-06-25 MX MX2010000672A patent/MX2010000672A/en active IP Right Grant
- 2008-06-25 AU AU2008278056A patent/AU2008278056B2/en not_active Ceased
- 2008-06-25 AT AT08773648T patent/ATE482939T1/en not_active IP Right Cessation
- 2008-06-25 WO PCT/EP2008/005142 patent/WO2009010163A1/en active Application Filing
- 2008-06-25 EA EA201070145A patent/EA017806B1/en not_active IP Right Cessation
- 2008-06-25 CA CA2693088A patent/CA2693088C/en active Active
- 2008-06-25 AP AP2010005131A patent/AP2010005131A0/en unknown
- 2008-06-25 EP EP08773648A patent/EP2176248B1/en active Active
- 2008-06-25 DE DE602008002843T patent/DE602008002843D1/en active Active
- 2008-06-25 CN CN2008800248917A patent/CN101809009B/en active Active
- 2008-06-25 UA UAA201001591A patent/UA99300C2/en unknown
- 2008-06-25 KR KR1020107003264A patent/KR101588064B1/en active IP Right Grant
-
2010
- 2010-01-13 TN TNP2010000023A patent/TN2010000023A1/en unknown
- 2010-01-15 NI NI201000012A patent/NI201000012A/en unknown
- 2010-01-21 ZA ZA201000491A patent/ZA201000491B/en unknown
- 2010-01-27 CR CR11240A patent/CR11240A/en not_active Application Discontinuation
- 2010-02-11 MA MA32614A patent/MA31607B1/en unknown
- 2010-02-12 EC EC2010009962A patent/ECSP109962A/en unknown
- 2010-02-16 CO CO10017435A patent/CO6321160A2/en not_active Application Discontinuation
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Cited By (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2380886A1 (en) | 2010-04-23 | 2011-10-26 | Vadim A. Makarov | Process for the preparation of 2-aminosubstituted 1,3-benzothiazine-4-ones |
WO2011132070A1 (en) | 2010-04-23 | 2011-10-27 | Makarov Vadim A | Process for the preparation of 2-amino-substituted 1,3-benzothiazine-4-ones |
KR20140012956A (en) * | 2010-11-19 | 2014-02-04 | 에꼴 뽈리떼끄닉 뻬데랄 드 로잔느 (으뻬에프엘) | 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
KR101871970B1 (en) | 2010-11-19 | 2018-08-02 | 에꼴 뽈리떼끄닉 뻬데랄 드 로잔느 (으뻬에프엘) | 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
WO2012066518A1 (en) | 2010-11-19 | 2012-05-24 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
CN103221399A (en) * | 2010-11-19 | 2013-07-24 | 洛桑联邦理工学院(Epfl) | 2-piperazin-1-l-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
JP2013542980A (en) * | 2010-11-19 | 2013-11-28 | エコール ポリテクニーク フェデラル ドゥ ローザンヌ (イーピーエフエル) | 2-Piperazin-1-yl-4H-1,3-benzothiazin-4-one derivatives and their use in treating infectious diseases in mammals |
AU2011330742B2 (en) * | 2010-11-19 | 2016-10-13 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-piperazin-1-yl-4H-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
US8796264B2 (en) | 2010-11-19 | 2014-08-05 | Ecole Polytechnique Federale De Lausanne (Epfl) | 2-piperazin-1-yl-4H-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
KR101851774B1 (en) | 2010-11-19 | 2018-04-25 | 에꼴 뽈리떼끄닉 뻬데랄 드 로잔느 (으뻬에프엘) | 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
CN107011287A (en) * | 2010-11-19 | 2017-08-04 | 洛桑联邦理工学院(Epfl) | The ketone derivatives of 2 piperazine, 1 base 4H, 1,3 benzothiazines 4 and its purposes for treating mammalian infections |
EA023879B1 (en) * | 2010-11-19 | 2016-07-29 | Эколь Политекник Федераль Де Лозанна (Эпфл) | 2-piperazin-1-yl-4h-1,3-benzothiazin-4-one derivatives and their use for the treatment of mammalian infections |
EP2468746A1 (en) | 2010-12-23 | 2012-06-27 | The University of Queensland | Benzothiazinone compounds and their use as anti-tuberculosis agents |
WO2012085654A1 (en) | 2010-12-23 | 2012-06-28 | The University Of Queensland | Novel anti-tuberculosis agents |
WO2013038259A1 (en) | 2011-09-15 | 2013-03-21 | The University Of Queensland | Benzothiazinone derivatives as anti -tuberculosis agents |
EP2570413A1 (en) | 2011-09-15 | 2013-03-20 | The University Of Queensland | Benzothiazinone derivatives as anti-tuberculosis agents |
US9708339B2 (en) * | 2014-06-09 | 2017-07-18 | University Of Notre Dame Du Lac | 1,3-benzothiazinone, sulfoxide, and sulfone compounds with electrophilic substituent |
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CN101809009A (en) | 2010-08-18 |
ATE482939T1 (en) | 2010-10-15 |
AU2008278056B2 (en) | 2013-09-26 |
BRPI0813828A2 (en) | 2015-01-06 |
US20100286130A1 (en) | 2010-11-11 |
DE602008002843D1 (en) | 2010-11-11 |
CO6321160A2 (en) | 2011-09-20 |
CA2693088A1 (en) | 2009-01-22 |
NZ582620A (en) | 2012-03-30 |
EP2020406A1 (en) | 2009-02-04 |
EA017806B1 (en) | 2013-03-29 |
CA2693088C (en) | 2016-08-30 |
UA99300C2 (en) | 2012-08-10 |
EA201070145A1 (en) | 2010-06-30 |
US8440842B2 (en) | 2013-05-14 |
EP2176248B1 (en) | 2010-09-29 |
JP5502731B2 (en) | 2014-05-28 |
AP2010005131A0 (en) | 2010-02-28 |
TN2010000023A1 (en) | 2011-09-26 |
MX2010000672A (en) | 2010-05-17 |
CR11240A (en) | 2010-05-19 |
KR20100043071A (en) | 2010-04-27 |
CN101809009B (en) | 2013-04-24 |
JP2010533661A (en) | 2010-10-28 |
EP2176248A1 (en) | 2010-04-21 |
MA31607B1 (en) | 2010-08-02 |
AU2008278056A1 (en) | 2009-01-22 |
NI201000012A (en) | 2010-05-14 |
ZA201000491B (en) | 2010-10-27 |
KR101588064B1 (en) | 2016-01-22 |
ECSP109962A (en) | 2010-03-31 |
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