WO2014161516A1 - Oxa- and thia-diazoles useful in the treatment of tuberculosis - Google Patents

Oxa- and thia-diazoles useful in the treatment of tuberculosis Download PDF

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WO2014161516A1
WO2014161516A1 PCT/CZ2013/000131 CZ2013000131W WO2014161516A1 WO 2014161516 A1 WO2014161516 A1 WO 2014161516A1 CZ 2013000131 W CZ2013000131 W CZ 2013000131W WO 2014161516 A1 WO2014161516 A1 WO 2014161516A1
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nmr
mhz
general formula
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compounds
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Alexandr Hrabalek
Jaroslav ROH
Galina KARABANOVICH
Vera KLIMESOVA
Jan NEMECEK
Petr PAVEK
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Univerzita Karlova V Praze Farmaceuticka Fakulta V Hradci Kralove
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to the new antituberculotics on the basis of nitro compounds, which are active against multidrug-resistant strains of mycobacteria.
  • Tuberculosis caused by Mycobacterium tuberculosis complex (M.tb), belongs to the most spread infection disease worldwide for many years. Despite the present antituberculotic treatment, incidence and mortality of TB is still high (World Health Organization, Stop TB Partnership. Tuberculosis Global Facts 2011/12). Combinations of pharmaceuticals with antimycobacterial effect are used for the treatment and they are administered usually for 6 - 9 months. For many years there are at disposal only 5 effective preparations referred as antituberculotics first-line. There are namely bactericidal active isoniazid, rifampicin, pyrazinamide, streptomycin, and bacteriostatic active ethambutol.
  • Drug-resistant strains require prolonging the treatment period for further up to two years with second-line drugs that are highly toxic, more expensive and less active that standard first-line drugs.
  • the treatment includes fluoroquinolones (ofloxacin, moxifloxacin), other members of rifamycin group (rifabutin, rifapentine), kanamycin, capreomycin, amikacin and older agents such as ethionamide, capreomycin, p-aminosalicylic acid.
  • TDR totally drug-resistance
  • TDR strains have further resistance to second-line drugs and are virtually incurable.
  • the great problem becomes the co-infection TB with HIV/ AIDS.
  • the World Health Organization one-third of world's population has latent form of TB. Infection with HIV suppresses the immune system and allows a latent infection to reactivate into an active form of TB.
  • common HIV antiretro viral therapies are not compatible with the current TB regimen. Co-infection TB and HIV is practically incurable.
  • New drugs have to be active against MDR strains, have to be compatible with antiretroviral therapy and to cope with the latent, non-replicating form of mycobacteria. These demands can carry out the new antituberculotic active drugs with novel mechanism of action.
  • New potential antituberculotics in preclinical and clinical phase of development are often compounds that contain a nitro group in their molecule.
  • nitroimidazol-oxazine - PA-824 (Singh, R.; Manjunatha, U.; Boshoff, H. I. M.; Ha, Y. H.; Niyomrattanakit, P.; Ledwidge, R.; Dowd, C. S.; Lee, I. Y.; Kim, P.; Zhang, L.; Kang, S.; Keller, T. H.; Jiricek, J. Barry, C. E. 3rd.
  • Bicyclic nitroimidazoles act as intracellular NO donors and kill non-replicating Mycobacterium tuberculosis. Science 2008, 322, 1392-1395), nitro-dihydroimidazo-oxazole OPC-67683 - Delamanid (Matsumoto, M.; Hashizume, H.; Tomishige, T.; Kawasaki, M.; Tsubouchi, H.; Sasaki, H.; Shimokawa, Y.; Komatsu, M. OPC-67683, and nitro-dihydro- imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLOSMedicine 2006, 3, 2131-2143),
  • BTZ043 benzothiazinone (Makarov, V.; Manina, G.; Mikusova, K.; Mollmann, U.; Ryabova, O.; Saint- Joanis, B.; Dhar, N.; Pasca, M.R.; Buroni, S.; Lucarelli, A.P.; Milano, A.; De Rossi, E.; Belanova, M.; Bobovska, A.; Dianiskova, P.; Kordulakova, J.; Sala, C; Fullnm, E.; Schneder, P.; McKinney, J.D.; Brodin, P.; Christophe, T.; Waddell, S.; Butcher, P.; Albrethesen, J.; Rosenkrands, I.; Brosch, R.; Nandi, V.; Bharath, S.; Gaonkar, S.; Shandil, R.K.; Balasubramanian, V.; Balganesh, T.; Ty
  • R 4-methoxyphenyl (DNB1) or benzyl (DNB2).
  • New compounds of general formula (I) show significant activity against Mycobacterium tuberculosis, against non-tuberculous mycobacteria and also against clinical isolates.
  • X is O or S;
  • R is selected from the group consisting of: H, NH 2 -, Ci-Cn alkyl, cyclohexyl-, benzyl-, phenyl-, pyridyl- or phenyl- substituted, in positions 2, 3, 4 or 5, with one or more electron- acceptor groups comprising -N0 2 , -N(alkyl) 3 , -CF 3 , CC1 3 , -CN, -COOH, -COOAlk, -COOAr, -CHO, -COAlk, -COAr, -F, -CI, -Br, -I, and/or electron-donor groups comprising -NH 2 , - NHalkyl, -N(alkyl) 2 , -OH, -Oalkyl, -Oaryl, -NHCOCH 3 , -NHCOalkyl; -NHCOaryl; -al
  • Another aspect of the invention is the use of the above mentioned substituted diazole of general formula (I) according to the current invention as antituberculotic agent.
  • Further aspect of the invention also relates to a pharmaceutical preparation containing the substituted diazole of general formula (I) as the active ingredient.
  • TBAB tetra-n-butylamonium bromide
  • the prepared compounds corresponding to general formula (I) were evaluated in Regional Institute of Public Health, Ostrava (Department for Diagnostic of Mycobacteria, Partyzanske namesti 7, 702 00 Ostrava) in in vitro conditions in Sula's semisynthetic liquid medium (SEVAC,ska) and the minimum inhibitory concentrations (MIC) were determined.
  • the antimycobacterial activity was tested against Czech National Collection strains Mycobacterium tuberculosis CNCTC My 331/88, M. avium CNCTC My 330/88, and M. kansasii CNCTC My 235/80, and a clinical isolate M. kansasii 6509/96.
  • Isoniazid (INH) was used as a standard in each assay. The results are shown in Table 4.
  • MDR strains Mycobacterium tuberculosis
  • the strains are labelled as M. tuberculosis 234/2005, M. tuberculosis 9449/2007, M. tuberculosis 8666/2010, M. tuberculosis Praha 1, M. tuberculosis Praha 4 and M. tuberculosis Praha 131.
  • These strains were clinically isolated from patients and are deposited in Regional Institute of Public Health, Ostrava (Department for Diagnostic of Mycobacteria, Partyzanske namesti 7, 702 00 Ostrava).
  • the most active compounds by general formula (I) were also evaluated for cytotoxicity according to the method CellTiter96® on cell line JEG3. Cell viability has not been influenced even at concentrations of the evaluated compounds of 10 ⁇ / ⁇ . In both toxicity tests, 100 times up to 200 times higher concentrations than the antituberculotic activity concentration were used.
  • the subject matter of the present invention comprises a combination of a certain five-membered nitrogen-containing heterocycle and the dinitrophenyl group which is bound to said heterocycle by a short methylsulfanyl linker group.
  • 2-(3,5-Dinitrobenzylsulfanyl)-5-methyl-l,3,4-oxadiazole (1) was prepared by reaction of 5-methyl-l,3,4-oxadiazole-5-thiol (0.1 g; 0,76 mmol) with 3,5-dinitrobenzyl chloride (0.15 g; 0.69 mmol) in the system of 5 ml CH 2 C1 2 / 5 ml H 2 0, in the presence of tetrabutylammonium bromide (22 mg; 0.07 mmol) and NaOH (33 mg; 0.83 mmol) at room temperature for 12 hours.
  • the starting 3,5-dinitrobenzyl chloride is a commercially available compound.
  • the starting 5-methyl-l,3,4-oxadiazole-5-thiol was prepared according to published procedures: a) Hoggarth, E. J. Chem. Soc. 1952, 4811. b) Lacasse, G.; Muchowski, J. M. Can. J. Chem. 1972, 50, 3082.)
  • 2-(3,5-Dinitrobenzylsulfanyl)-5-phenyl-l,3,4-oxadiazole (2) was prepared by reaction of 5-phenyl-l,3,4-oxadiazole-5-thiol (O.lg; 0.56 mmol) with 3,5-dinitrobenzyl chloride (0.11 g; 0.51 mmol) in the system of 5 ml C3 ⁇ 4C1 2 / 5 ml H 2 0, in the presence of tetrabutylammonium bromide (16 mg; 0.05 mmol) and NaOH (25 mg; 0.61 mmol) at room temperature for 24 hours.
  • the starting 3,5-dinitrobenzyl chloride is a commercially available compound.
  • the starting 5-phenyl-l,3,4-oxadiazole-5-thiol was prepared according to published procedures: a) Baron, M.; Wilson, C. V.: J. Org. Chem. 1958, 23 (7), 1021-1023; b) Zarghi, A.; Faizi, M.; Shafaghi, B.; Ahadian, A.; Khojastehpoor, H. R.; Zanganeh, V.; Tabatabai, S. A.; Shafiee, A.: Bioorg. Med. Chem. Lett. 2005, 15 (12), 3126-3129; c) Wei, M.
  • 2-(2,4-Dinitrobenzylsulfanyl)-5-phenyl-l,3,4-oxadiazole (16) was prepared by reaction of 5-phenyl-l,3,4-oxadiazole-5-thiol (0.1 g; 0.56 mmol) with 2,4-dinitrobenzyl chloride (0.1 1 g; 0.51 mmol) in the system of 5 ml CH 2 C1 2 / 5 ml H 2 0, in the presence of tetrabutylammonium bromide (16 mg; 0.05 mmol) and NaOH (25 mg; 0.61 mmol) at room temperature for 24 hours.
  • the starting 2,4-dinitrobenzyl chloride is a commercially available compound.
  • the starting 5-phenyl-l,3,4-oxadiazole-5-thiol was prepared according to published procedures: a) Baron, M; Wilson, C. V.: J. Org. Chem. 1958, 23 (7), 1021-1023; b) Zarghi, A.; Faizi, M; Shafaghi, B.; Ahadian, A.; Khojastehpoor, H. R.; Zanganeh, V.; Tabatabai, S. A.; Shafiee, A.: Bioorg. Med. Chem. Lett. 2005, 15 (12), 3126-3129; c) Hasan, A.; Thomas, N. F.; Gapil, S.: Molecules 2011 , 16 (2), 1297-1309.).
  • 2-(3,5-Dimtrobenzylsulfanyl)-5-methyl-l,3,4-thiadiazole (22) was prepared by reaction of 5-methyl-l,3,4-thiadiazole-5-thiol (0.165 g; 1.24 mmol) with 3, 5 -dinitrobenzyl chloride (0.246 g; 1.14 mmol) in the system of 5 ml CH 2 C1 2 / 5 ml 3 ⁇ 40, in the presence of tetrabutylammonium bromide (32 mg; 0.1 mmol) and NaOH (54 mg; 1.35 mmol) at room temperature for 12 hours.
  • 2-Amino-5-(3,5-dinitrobenzylsulfanyl)-l,3,4-thiadiazole (23) was prepared by reaction of 5-amino-l,3,4-thiadiazole-5-thiol (0.165 g; 1.24 mmol) with 3, 5 -dinitrobenzyl chloride (0.246 g; 1.14 mmol) in the system of 5 ml CH2CI2/ 5 ml H 2 0, in the presence of tetrabutylammonium bromide (32 mg; 0.1 mmol) and NaOH (54 mg; 1.35 mmol) at room temperature for 12 hours.
  • 2-(3,5-Dinitrobenzylsulfanyl)-5-phenyl-l,3,4-thiadiazole (25) was prepared by reaction of 5-phenyl-l,3,4-thiadiazole-5-thiol (0.1 g; 0.51 mmol) with 3,5 -dinitrobenzyl chloride (0.1 g; 0.46 mmol) in the system of 5 ml CH 2 C1 2 / 5 ml H 2 0, in the presence of tetrabutyl-ammonium bromide (16 mg; 0.05 mmol) and NaOH (23 mg; 0.57 mmol) at room temperature for 24 hours.
  • the starting 3, 5 -dinitrobenzyl chloride is a commercially available compound.
  • the starting 5-phenyl-l,3,4-thiadiazole-5-thiol was prepared according to published procedures: (a) Baron, M.; Wilson, C. V.: J. Org. Chem. 1958, 23 (7), 1021-1023; b) Wei, M. X.; Feng, L.; Li, X. Q.; Zhou, X. Z.; Shao, Z. H.: Eur. J. Med. Chem. 2009, 44 (8), 3340-3344).
  • Table 4 The minimum inhibitory concentration in vitro (expressed in ⁇ . ⁇ 1 ) of compounds of general formula (I) (micromethod for determination of minimum inhibitory concentration in Sula ' s semisynthetic medium on plastic P-microplates; MICs determined after incubation at 37 °C for 14 and 21 days for M. tuberculosis and M. avium, for 7, 14 and 21 days for M. kansasii).
  • Table 5a The minimum inhibitory concentration in vitro (expressed in ⁇ . ⁇ ) of selected antibiotics and antituberculotics (micromethod for determination of minimum inhibitory concentration in Sula ' s semisynthetic medium on plastic P-microplates after incubation for 14 and 21 days) for multidrug resistant strains of M. tuberculosis
  • Table 5b The minimum inhibitory concentration in vitro (expressed in ⁇ . ) of compounds by general formula (I) (micromethod for determination of minimum inhibitory concentration in Sula ' s semisynthetic medium on plastic P-microplates) after incubation at 37 °C for 14 and 21 days for multidrug resistant strains of M. tuberculosis M. tuberculosis (MDR strains)
  • the medicinal substance is mixed together with other individual excipients and the obtained mixture is compressed by regular manner using a conventional tablet machine.
  • Example 8 (content of active substance 300 m )
  • Example 9 (content of active substance 400 m )
  • Medicinal substance of general formula (I) 3 500.0 mg Potato starch 96.0 mg Lactose 54.0 g 15.0 g
  • the therapeutically effective compound is mixed with lactose, potato starch and this mixture is granulated with povidone.
  • the dried granulate is mixed then with sodium carboxymethyl- starch, magnesium stearate, and talc.
  • the obtained mixture is compressed by regular manner using a conventional tablet machine.

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  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
PCT/CZ2013/000131 2013-04-04 2013-10-16 Oxa- and thia-diazoles useful in the treatment of tuberculosis WO2014161516A1 (en)

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016091228A1 (en) * 2014-12-11 2016-06-16 Univerzita Karlova V Praze Substituted phenyltetrazole, its use and pharmaceutical preparation containing it
CZ306321B6 (cs) * 2014-12-11 2016-11-30 Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Substituovaný dinitrofenyltetrazol, jeho použití a farmaceutický přípravek ho obsahující
CZ306408B6 (cs) * 2014-12-11 2017-01-11 Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Dinitrofenyloxadiazol nebo -triazol, jeho použití a farmaceutický přípravek ho obsahující
EP3210469A1 (de) 2016-02-23 2017-08-30 Bayer Cropscience AG Verwendung von substituierten thio-1,2,4-triazolen zur steigerung der stresstoleranz in pflanzen
WO2020128675A1 (en) 2018-11-30 2020-06-25 Svenox Pharmaceuticals Llc Substituted 1,2,4-oxadiazole, its application and a pharmaceutical preparation comprising it
WO2021040519A1 (en) * 2019-08-26 2021-03-04 Stichting Vumc Inhibition of mycobacterial type vii secretion
US11905263B1 (en) 2023-10-13 2024-02-20 King Faisal University 4-nitro-N′-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11932632B1 (en) 2023-10-13 2024-03-19 King Faisal University N'-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzo[d][1,3]dioxole-5 carboximidamide as an antimicrobial compound

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5442617B2 (cs) * 1974-12-28 1979-12-15
AR032653A1 (es) * 2001-02-09 2003-11-19 Telik Inc Inhibidores heterociclicos del trasportador de glicina 2 composiciones farmaceuticas, uso y metodos.
JP2010507619A (ja) * 2006-10-25 2010-03-11 ノイロサーチ アクティーゼルスカブ オキサジアゾール及びチアジアゾール化合物並びにニコチン性アセチルコリン受容体調節物質としてのその使用
DE102011106990B3 (de) * 2011-07-08 2013-01-03 Technische Universität Darmstadt Verbindungen als Glykogen Synthase Kinase 3 (GSK-3) Inhibitoren für die Behandlung von GSK-3-vermittelten Erkrankungen
US10301294B2 (en) * 2013-03-13 2019-05-28 The Broad Institute Inc. Compounds for the treatment of tuberculosis

Non-Patent Citations (19)

* Cited by examiner, † Cited by third party
Title
"Bicyclic nitroimidazoles act as intracellular NO donors and kill non-replicating Mycobacterium tuberculosis", SCIENCE, vol. 322, 2008, pages 1392 - 1395
"Tuberculosis Global Facts", December 2011, WORLD HEALTH ORGANIZATION, article "Stop TB Partnership"
ALIREZA FOROUMADI ET AL: "Antituberculosis agents. V. Synthesis, evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(5-nitro-2-furyl)-1,3,4- thiadiazole derivatives", IL FARMACO, vol. 57, no. 9, 1 September 2002 (2002-09-01), pages 765 - 769, XP055088385, ISSN: 0014-827X, DOI: 10.1016/S0014-827X(02)01277-6 *
BARON, M.; WILSON, C. V., J. ORG. CHEM., vol. 23, no. 7, 1958, pages 1021 - 1023
CHRISTOPHE, T.; JACKSON, M.; JEON, H.K.; FENISTEIN, D.; CONTRERAS-DOMINGUEZ, M.; KIM, J.; GENOVESIO, A.; CARRALOT, J.P.; EWANN, F.: "High content screening identifies decaprenyl-phosphoribose 2'epimerase as a target for intracellular antimycobacterial inhibitors.", PLOS PATHOG, vol. 5, 2009, pages 1 - 10
CLAYDEN, N. GREEVES; S. WARREN; P. WOTHERS: "Organic Chemistry", 2001, OXFORD UNIVERSITY PRESS
FOROUMADI A. ET AL.: "Antituberculosis agents. V. Synthesis, evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(5-nitro-2-furyl)-1,3,4-thiadiazole derivatives", IL FARMACO, vol. 57, no. 9, 2002, pages 765 - 769
HASAN, A.; THOMAS, N. F.; GAPIL, S., MOLECULES, vol. 16, no. 2, 2011, pages 1297 - 1309
HOGGARTH, E., J. CHEM. SOC., 1952, pages 4811
JOHN MCMURRY: "Organic Chemistry", 2004, THOMSON LEARNING COMPANY
KLIMESOVA V ET AL: "Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives", IL FARMACO, ELSEVIER FRANCE * EDITIONS SCIENTIFIQUES ET MEDICALES, IT, vol. 59, no. 4, 1 April 2004 (2004-04-01), pages 279 - 288, XP027433920, ISSN: 0014-827X, [retrieved on 20040408], DOI: 10.1016/J.FARMAC.2004.01.006 *
KLIMESOVA V. ET AL.: "Synthesis and antimycobacterial activity of 1,2,4-triazole-3-benzylsulfanyl derivatives", IL FARMACO, vol. 59, no. 4, 2004, pages 279 - 288
L. G. WADE, JR.: "Organic Chemistry", 2006, PEARSON PRENTICE HALL INC.
LACASSE, G.; MUCHOWSKI, J. M., CAN. J. CHEM., vol. 50, 1972, pages 3082
MAKAROV, V.; MANINA, G; MIKUSOVA, K.; MOLLMANN, U.; RYABOVA, 0.; SAINT-JOANIS, B.; DHAR, N.; PASCA, M.R.; BURONI, S.; LUCARELLI, A: "Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis", SCIENCE, vol. 324, 2009, pages 801 - 804
MATSUMOTO, M.; HASHIZUME, H.; TOMISHIGE, T.; KAWASAKI, M.; TSUBOUCHI, H.; SASAKI, H.; SHIMOKAWA, Y.; KOMATSU, M.: "OPC-67683, and nitro-dihydro- imidazooxazole derivative with promising action against tuberculosis in vitro and in mice", PLOSMEDICINE, vol. 3, 2006, pages 2131 - 2143
NAVARRETE-VAZQUEZ ET AL: "Synthesis and antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines", BIOORGANIC & MEDICINAL CHEMISTRY, PERGAMON, GB, vol. 15, no. 16, 22 June 2007 (2007-06-22), pages 5502 - 5508, XP022130593, ISSN: 0968-0896, DOI: 10.1016/J.BMC.2007.05.053 *
WEI, M. X.; FENG, L.; LI, X. Q.; ZHOU, X. Z.; SHAO, Z. H., EUR. J. MED. CHEM., vol. 44, no. 8, 2009, pages 3340 - 3344
ZARGHI, A.; FAIZI, M.; SHAFAGHI, B.; AHADIAN, A.; KHOJASTEHPOOR, H. R.; ZANGANEH, V.; TABATABAI, S. A.; SHAFIEE, A., BIOORG. MED. CHEM. LETT., vol. 15, no. 12, 2005, pages 3126 - 3129

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016091228A1 (en) * 2014-12-11 2016-06-16 Univerzita Karlova V Praze Substituted phenyltetrazole, its use and pharmaceutical preparation containing it
CZ306321B6 (cs) * 2014-12-11 2016-11-30 Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Substituovaný dinitrofenyltetrazol, jeho použití a farmaceutický přípravek ho obsahující
CZ306408B6 (cs) * 2014-12-11 2017-01-11 Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Dinitrofenyloxadiazol nebo -triazol, jeho použití a farmaceutický přípravek ho obsahující
EP3210469A1 (de) 2016-02-23 2017-08-30 Bayer Cropscience AG Verwendung von substituierten thio-1,2,4-triazolen zur steigerung der stresstoleranz in pflanzen
WO2020128675A1 (en) 2018-11-30 2020-06-25 Svenox Pharmaceuticals Llc Substituted 1,2,4-oxadiazole, its application and a pharmaceutical preparation comprising it
CZ308557B6 (cs) * 2018-11-30 2020-11-25 Svenox Pharmaceuticals Llc Substituovaný 1,2,4-oxadiazol, jeho použití a farmaceutický přípravek ho obsahující
CN112996565A (zh) * 2018-11-30 2021-06-18 斯文诺克斯制药有限责任公司 取代的1,2,4-噁二唑、其应用和包含它的药物制剂
US20210403443A1 (en) * 2018-11-30 2021-12-30 Svenox Pharmaceuticals Llc Substituted 1,2,4-oxadiazole, its application and a pharmaceutical preparation comprising it
WO2021040519A1 (en) * 2019-08-26 2021-03-04 Stichting Vumc Inhibition of mycobacterial type vii secretion
US11905263B1 (en) 2023-10-13 2024-02-20 King Faisal University 4-nitro-N′-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzimidamide as an antimicrobial compound
US11932632B1 (en) 2023-10-13 2024-03-19 King Faisal University N'-(2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)acetoxy)benzo[d][1,3]dioxole-5 carboximidamide as an antimicrobial compound

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