Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
  • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
  • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
  • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

• the compounds of this invention are nitroimidazolyl pyrimidines of the general Formula I N N II II 0211 I I and physiologically acceptable salts thereof, wherein X is alkyl of 1-4 carbon atoms, R and R which can be alike or different, are a hydrogen atom, alkyl of one to four carbon atoms, phenyl, trifluoromethyl or a thienyl group, and R is a hydrogen atom, alkyl of 1-4 carbon atoms, hydroxyalkoxy of 2-4 carbon atoms, which can be esterified by alkanoic acid of l-4 carbon atoms, i.e., alkanoyloxyalkoxy, oxoalkyl, i.e., keto substituted alkyl, containing a total of 3-6 carbon atoms, or when R;
• R is phenyl, an alkylene having l-2 carbon atoms in the chain joined to the 2-position of the phenyl ring.
• alkyl of 1-4 carbon atoms are methyl, ethyl, n-propyl, isobutyl, etc., preferably methyl.
• hydroxyalkoxy and esters thereof of an alkanoic acid are hydroxyethyl, 2-hydroxypropyl, 3- hydroxypropyl, acetoxyethyl, propionyloxyethyl and 3-acetoxypropy1.
• oxoalkyl examples include acetylmethyl, acetylethyl and propionylmethyl.
• physiologically acceptable acids which can be employed to form the acid addition of salts of this invention are inorganic acids, e.g., hydrochloric acid, sulfuric acid, etc., and organic mono-, diand tricarboxylic acids, e.g., acetic acid, propionic acid, lactic acid, citric acid, benzoic acid, succinic acid, heptagluconic acid, etc.
• inorganic acids e.g., hydrochloric acid, sulfuric acid, etc.
• organic mono-, diand tricarboxylic acids e.g., acetic acid, propionic acid, lactic acid, citric acid, benzoic acid, succinic acid, heptagluconic acid, etc.
• the exact nature of the acid is not critical, so long as it forms a physiologically acceptable acid addition salt.
• novel compounds of this invention can be produced in a conventional manner, for example, by reacting an amidine of the general Formula II N NH 1 l -c 11 OZN N wherein X has the values given above, or a salt thereof, preferably the hydrochloride.
• R R and R have the values given above, or a reactive functional derivative thereof, and subsequently saponifying any acyloxy groups present in' the condensation product to hydroxy groups, or esterifying free hydroxy groups, and optionally converting the compounds into the salts thereof with inorganic or organic acids.
• Suitable derivatives of the dicarbonyl compound are reactive derivatives such as, for example, the acetal or, if R and R both are H, an enamine.
• reaction of the amidine (II) and/or the salt thereof, the latter optionally mixed with ammonium chloride, with the B-dicarbonyl compounds or the derivatives thereof can be effected in the absence or in the presence of a solvent, e.g., acetic acid, acetic anhydride, dimethylformamide, alcohol, to which can be Minimum inhibitory Concentration Against Trichomonas Vaginalis Compound g/ml.)
• a solvent e.g., acetic acid, acetic anhydride, dimethylformamide, alcohol
• Thenovel compounds can be administered topically or systemically in the pharmaceutically customary forms of application, such as pills, dragees, capsules,
• PREPARATION 9.9 g. (50 millimoles) of the ethyl ester of S-nitro-lmethyl-2-imidazolyl-iminocarboxylic acid and 2.7 g. (50 millimoles) of pulverized ammonium chloride are boiled for 72 hours in methanol. After evaporation of the solvent, the residue is digested in the hot state with 100 ml. of ethyl acetate; yield: 6.1 g. (47% of theory) of an equimolar mixture of 5-nitro-l-methyl-2-imidazolylcarboxamidinium chloride and ammonium chloride; m.p. 225-227 C.
• EXAMPLE 1 4,6-Dimethyl-2-( 5 -nitrol -methyl-2-imidazolyl pyrimidine 0.52 g. (2 millimoles) of an equimolar mixture of 5- nitro-l -methyl-2-imidazolyl-carboxamidinium chloride and ammonium chloride, 0.21 g. (2.1 millilmoles) of acetylacetone, and 0.33 g. of anhydrous sodium acetate are boiled in 4 ml. of acetic acid for 2 hours. Thereafter, the reaction mixture is concentrated to dryness, the residue is triturated with water, and recrystallized from isopropanol. Yield: 0.32 g. (69% of theory), m.p. l48l 50 C.
• EXAMPLE 3 5-( 2-Acetoxyethoxy)-2-( 5-nitrol -methyl-2- imidazolyl )-pyrimidine
• the compound is obtained analogously to Example 1 with 3-dimethylamino-2(2-hydroxyethoxy)-acrolein; in this process, acetic anhydride can also be employed in place of acetic acid.
• acetic anhydride can also be employed in place of acetic acid.
• the residue is mixed with water, the product is extracted with ethyl acetate, and the residue of the ethyl acetate extract is triturated with methanol; m.p. l48l50 C.
• EXAMPLE 5 5-( 2-Hydroxyethoxy)-2-( S-nitrol -methyl-2- imidazolyl)-pyrimidine Hydrochloride 0.78 g. (5 millimoles) of 3-dimethylamino-2-(2- hydroxyethoxy)-acrolein and 1.3 g. (5 millimoles) of an equimolar mixture of S-nitro-l-methyl-2-imidazolylcarboxamidinium chloride and ammonium chloride are added to 5 ml. of 1N sodium methylate solution in methanol. After refluxing for 20 hours, the methanol is distilled off, the residue is maintained at C. for 30 minutes, and mixed with water.
• the product is extracted with ethyl acetate, the ethyl acetate is concentrated, and the residue is digested with isopropanol.
• the thus-obtained free base is converted, with methanolic hydrochloric acid, into the hydrochloride, m.p. l58l60 C.
• the same product is obtained by heating equimolar amounts of S-nitro-l-methyl-Z-imidazolyl-carboxamidine and 3-dimethylamino-2-(2-hydroxyethoxy)- acrolein in dimethylformamide or without solvent and converting the mixture thus obtained optionally after removing the solvent by evaporation into the hydrochloride.
• EXAMPLE 6 5-( 2-Acetoxyethoxy )-2-( S-nitrol -methyl-2- imidazolyl )-pyrimidine 0.29 g. (l millimole) of 5-(2-hydroxyethoxy)-2-(5- nitro-l -methyl-2-imidazolyl)-pyrimidine hydrochloride means of preparative layer chromatography; m.p. 1 C. (from ethyl acetate).
• EXAMPLE 8 4,6-Dimethyl-5-( Z-acetylethyl )-2-( 5-nitrol -methyl-2- imidazolyl )-pyrimidine
• the compound is obtained analogously to Example 7 with 3-acetyl-2,6-heptanedione; m.p. 142 C. (from ethyl acetate).
• EXAMPLE 10 4-Trifluoromethyl-2-( S-nitro- 1 -methyl-2-imidazolyl 6-(2-thienyl)-pyrimidine The compound is obtained in accordance with Example 7 with l-thenoyl-3,3,3-trifluoroacetone. Purification is effected by recrystallization from ethyl acetate; m.p. 188 C.
• EXAMPLE 11 4-Methyl-6-phenyl-2-(S-nitro-1-methyl-2'imidazolyl)- pyrimidine The compound is obtained in analogy to Example 7 with Z-acetylacetophenone. The product is purified by recrystallization from ethyl acetate; m.p. C.
• X is methyl.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Plural Heterocyclic Compounds (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Cited By (5)

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  • BE BE795636D patent/BE795636A/xx unknown
• 1972
  • 1972-12-27 DD DD167919A patent/DD105226A5/xx unknown
• 1973
  • 1973-02-09 US US331114A patent/US3920655A/en not_active Expired - Lifetime
  • 1973-02-16 AT AT141973A patent/AT328455B/de not_active IP Right Cessation
  • 1973-02-16 FR FR7305530A patent/FR2183670B1/fr not_active Expired
  • 1973-02-16 CH CH227973A patent/CH577995A5/xx not_active IP Right Cessation
  • 1973-02-19 GB GB794173A patent/GB1425261A/en not_active Expired
  • 1973-02-19 AU AU52334/73A patent/AU5233473A/en not_active Expired
  • 1973-02-19 NL NL7302292A patent/NL7302292A/xx not_active Application Discontinuation
  • 1973-02-19 JP JP48020097A patent/JPS4886881A/ja active Pending
  • 1973-02-19 CA CA164,004A patent/CA974242A/en not_active Expired

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