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WO1986002927A1 - Derives de 1,2,4-thiadiazole - Google Patents

Derives de 1,2,4-thiadiazole Download PDF

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Publication number
WO1986002927A1
WO1986002927A1 PCT/JP1985/000617 JP8500617W WO8602927A1 WO 1986002927 A1 WO1986002927 A1 WO 1986002927A1 JP 8500617 W JP8500617 W JP 8500617W WO 8602927 A1 WO8602927 A1 WO 8602927A1
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WO
WIPO (PCT)
Prior art keywords
group
formula
represented
halogen atom
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP1985/000617
Other languages
English (en)
Japanese (ja)
Inventor
Daigaku Takiguchi
Saburo Kano
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nippon Soda Co Ltd
Original Assignee
Nippon Soda Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nippon Soda Co Ltd filed Critical Nippon Soda Co Ltd
Publication of WO1986002927A1 publication Critical patent/WO1986002927A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
    • 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
    • C07D417/12—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 linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a novel 1,2,4-thiadiazole derivative having a bactericidal and protozoalicidal action against pathogenic microorganisms such as candidiasis, trichomoniasis, and dermatophytosis, and a method for producing the same.
  • pathogenic microorganisms such as candidiasis, trichomoniasis, and dermatophytosis
  • a compound similar to the compound of the present invention has the general formula
  • the present invention has the general formula
  • R represents a hydrogen atom, a halogen atom, 1-4 alkyl group, Application Benefits Full Affairs Lome butyl group, a phenyl group or a Ct ⁇ 4 ⁇ alkoxy group, '
  • n 0, 1 or 2;
  • A is a group represented by the formula Q , a group represented by the formula, or a group represented by the formula:
  • X is optionally substituted with a halogen atom or a halogen atom ( ⁇ 1-4 alkyl group, m is 0, 1 or 2,
  • B represents CH, N or N
  • r 3, r 4, r 5, r 6, r 7 and r 8 each represent a hydrogen atom, human Dorokishi group or C t ⁇ 4 alkyl groups k and j Waso respectively! : Indicates 2 or 3.
  • Q is a group represented by Formula 1,
  • r 9 may be substituted with a halogen atom, a 4- anolealkyl group, a C 1-4 alkoxy group,
  • E and D represent CH, N or N, respectively (however, E and D
  • D is not simultaneously N or N.
  • r 1 and iota ⁇ 2 are each a hydrogen atom, a halogen atom or an-alkyl group Y represents a 0, CH 2, S or S0 2.
  • Hal represents a halogen atom
  • ⁇ represents 1 or 2
  • the condensation reaction between the compound represented by the general formula ( ⁇ ) and the compound represented by the general formula ( ⁇ ) is performed in the presence of a base in a solvent.
  • -Between 20'C and 150 preferably between 10'c and 80'c for 10 minutes to several roars.
  • Examples of the base to be used include alkali metal hydroxides such as sodium hydroxide and sodium hydroxide, sodium hydride, alkali metal hydrides such as hydrogenation sodium, and the like.
  • Usual bases such as alcoholic alcohols such as sodium methylate and tertiary amines such as triethylamine can be mentioned.
  • the solvent used depends on the type of base, such as ice, alcohols, benzene, tonolenene, xylene, DMF, DMSO, ether, THF, dioxane and HMPA. Solvents can be used.
  • organic peracids such as perbenzoic acid and hydrogen peroxide can be used.
  • the reaction is carried out in a solvent when synthesizing a compound of the general formula [I] wherein T1 is 1 in a solvent.
  • the reaction is performed with 1.2 equivalents or less of the compound represented by
  • n 1 or 2 '
  • the solvent used depends on the type of oxidizing agent, such as water, organic acids such as acetic acid, and ketones such as clog form, methylene chloride, and acetate. And the like are appropriately selected.
  • the desired product can be obtained by performing ordinary post-treatment.
  • T represents an alkali metal atom.
  • the compound in the general formula [I], can also be produced according to the following reaction formula depending on the type of the substituent represented by ⁇ .
  • the structure of the compound obtained in this way was determined from the results of analysis of IR, NMR, MASS, spectrum, and the like.
  • the benzene layer was washed with water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and 5-[4-1 (phenoxy) phenylthio]-1,2, 4-thiadiazole 4.0 g (14 mmol, Yield 94%).
  • To 4.0 g (14 mmol) of the obtained compound was added 50 mL of a form of black mouth and 9.lg (37 mmol) of 70% methanol perbenzoic acid, and the mixture was heated and refluxed for 4 hours.
  • the black hole form layer was separated, washed twice with cold water, dried over anhydrous magnesium sulfate, and the black hole form was distilled off under reduced pressure.
  • 3 Dachiru 5 — [4 — (4-Trifluoromethyl benzene) benzenesulfonyl] 1, 1, 2, 4 — 3.8 g of thiadiazole crystals were obtained. This was recrystallized from cyclohexane to obtain a purified product. Melting point 80.5-81.5, TLC; silica gel-benzene single spot, H 1 —NMR; 52
  • Example 2 7.0 g (22 mmol) of the compound obtained in Example 1 was dissolved in 30 m of 1,2-dichloropentane, and 7 g of 25% fuming sulfuric acid was added thereto at 0 ° C with stirring for 0 min. . It was kept on ice for 1 hour, then heated and kept at 15'c for 1 hour. After distilling off 1,2-dichloroethane under reduced pressure, 40 g of ice was added to the obtained tar-like substance, followed by stirring and filtration to obtain a clear aqueous solution. This was cooled on ice and neutralized with a 20% aqueous sodium hydroxide solution. Crystals of sodium salt were deposited.
  • 1,4 g of 4'-methyl biphenyl 4 -thiol was dissolved in 30 m of ethanol, cooled to 110 ° C, and 1.4 g of 28% sodium methoxide was added. To this was added dropwise 1.3 g of 5-bromo-1,2,4-thiadiazole in 10 m of ethanol. After completion of the dropwise addition, the mixture was stirred at room temperature for 1 hour, and further heated under reflux for 10 minutes.
  • Table 1 shows typical examples of the compounds of the present invention produced in the same manner.
  • the compounds of the present invention are effective against pathogenic microorganisms such as candidiasis, trichomoniasis, dermatophytosis, etc., and exhibit an antibacterial activity superior to known compounds, particularly against candidiasis, and Skin No primary irritation is expected, and development as an antifungal agent is expected.
  • the antibacterial activity was measured by the agar plate dilution method using a microplate.
  • the test compound was dissolved in DMS0 to prepare a 100-fold solution of the final test concentration, and the mixture was added to the Sabrobe dextrose agar medium heated at 50 to 1: 100 and stirred well.
  • m to My Plate [Fa Icon 3047
  • Candida albicans IFO 0579 as a test bacterium, the antibacterial activity was measured by an agar plate dilution method using microplates. That is, the test compound was dissolved in DMS0 to prepare a 100-fold solution of the final test concentration, and the mixture was added to a Sabouraud glucose agar medium heated to 50% in a ratio of 1: 100, and the mixture was stirred well. Then, 1 m of the microplate was used for microplate [Falcon 3047 (registered trademark)].
  • the compounds were applied to Polyethylene glycol ointment (400 60% and 1540 40%) at 1% and 5 10%, applied to New Zealand white heron shaved skin, Draze, JH (J. pharm. Exp. Therap. 82, 377-390, 1944) to determine the primary stimulus rate (PII).
  • PII primary stimulus rate

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Composés représentés par la formule (I), où R représente hydrogène, halogène, alkyle comportant de 1 à 4 atomes de C, trifluorométhyle, phényle ou alkoxy comportant de 1 à 4 atomes de C, n représente 0,1 ou 2, A représente (II), où X représente un halogène ou éventuellement un alkyle substitué par un halogène et comportant de 1 à 4 atomes de C, m représente 0,1 ou 2, B représente CH, N ou (III), W représente -O-, un composé de formule (IV) (où r3, r4. r5, r6, r7 et r8 représentent chacun hydrogène, hydroxy ou un alkyle comportant de 1 à 4 atomes de C, k et j représentent chacun 1, 2 ou 3), l représente 0 ou 1, Q représente aryle tel que phényle substitué, pyridyle substitué, etc., E et D représentent chacun CH, N ou (III) (à condition que E et D ne représentent N ou (III) en même temps), et r1 et r2 représentent chacun hydrogène, halogène ou un alkyle comportant de 1 à 4 atomes de C, et Y représente 0,CH2, S ou SO2, à condition que les symboles $(1,5)$ entre les positions 1 et 2 et entre les positions 3 et 4 dans le système tricyclique contenant Y représentent chacun une liaison simple ou double. Ces composés présentent des effets fongicides et antiprotozoaires contre les candidoses, le trichomonas, les mycoses, etc.
PCT/JP1985/000617 1984-11-08 1985-11-06 Derives de 1,2,4-thiadiazole Ceased WO1986002927A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP23421584 1984-11-08
JP59/234215 1984-11-08

Publications (1)

Publication Number Publication Date
WO1986002927A1 true WO1986002927A1 (fr) 1986-05-22

Family

ID=16967496

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1985/000617 Ceased WO1986002927A1 (fr) 1984-11-08 1985-11-06 Derives de 1,2,4-thiadiazole

Country Status (2)

Country Link
AU (1) AU5067985A (fr)
WO (1) WO1986002927A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006095205A1 (fr) * 2005-03-09 2006-09-14 Merck Sharp & Dohme Limited Heteroarylsulfonylstilbenes en tant qu'antagonistes de 5-ht2a

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0623328B2 (ja) * 1987-03-09 1994-03-30 ポリプラスチックス株式会社 導線用被覆材

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5661370A (en) * 1979-10-26 1981-05-26 Nippon Soda Co Ltd 1,2,4-thiadiazole derivative, its preparation and agricultural and horticultural and medical germicide
DD222770A1 (de) * 1984-03-14 1985-05-29 Bitterfeld Chemie Fungizide mittel

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5661370A (en) * 1979-10-26 1981-05-26 Nippon Soda Co Ltd 1,2,4-thiadiazole derivative, its preparation and agricultural and horticultural and medical germicide
DD222770A1 (de) * 1984-03-14 1985-05-29 Bitterfeld Chemie Fungizide mittel

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, 99(17):139863w (1983), (Columbus, USA), "Production of Etridiazole and Its Analogs". *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006095205A1 (fr) * 2005-03-09 2006-09-14 Merck Sharp & Dohme Limited Heteroarylsulfonylstilbenes en tant qu'antagonistes de 5-ht2a

Also Published As

Publication number Publication date
AU5067985A (en) 1986-06-03

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