Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
  • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
  • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim

Definitions

• X represents in which R is selected from the group consisting of hydrogen, lower alkyl, hydroxy (lower) alkyl, lower alkoxyalkyl and amino; and R is selected from the group consisting of hydroxy (lower) alkyl, lower alkoxyalkyl and morpholinopropyl.
• the compounds of this invention bearing the group, in which R and R have the significance above related, in the 4-position are particularly distinguished by their ability to inhibit the growth of microorganisms.
• Representative of the very high order of antimicrobial activity resident in the members of this series is the effect elicited by the compound 4-[ bis-(2 hydroxyethyl)amino] 2-(5-nitro-2-furyl)quinazoline against a broad spectrum of gram-positive and gram-negative organisms under the commonly employed serial dilution technique:
• these compounds are adapted to be combined with suitable carriers in the form of dusts, suspensions, ointment, sprays and the like to provide compositions designed to prevent and eradicate bacterial contamination.
• the compounds of this invent-ion having the substituent are also capable of suppressing systemic infection in animals provoked by Staphylococcus aureus. When administered perorally in a dose of from 50-200 mgL/kg. to mice lethally infected with that bacterium, protect-ion against mortality is secured.
• an inert solvent in which the desired end product has low solubility such as water or petroleum ether, is conveniently added to the mixture to evoke the separation of solid material, which is secured by filtration and purified, if necessary or desirable, to yield the desired end product.
• the prodnot (208 g.) is purified by Soxhlet extraction with toluene.
• the toluene solution is chilled and filtered.
• the product is obtained as long, yellow needles melting at 196.5-198.5 in ayield of 106 g.
• EXAMPLE II 4- [Z-lzydroxyethyl(Z-hydro-xy propyl) amino] -2- (S-nirro- Z-fmyl) quinazoline (NF-1174)
• the solution is heated on a steam bath for 1 hour.
• the solution is diluted with water until a solid begins to separate.
• EXAMPLE III 4-b1's(2-hydr0xypr0pyl)amino-2-(5-nitr0-2-furyl) quinazoline (NF-1144)
• a 1 l., three-neck flask, fitted with a stirrer, is charged with 40 g. (0.145 mole) of the compound of Example I, B., and 40 g. (0.3 mole) of 1,1-iminodi-2-propanol in 500 ml. of dimethylformamide.
• the solution is heated on a steam bath for 2 hours.
• the solution is diluted with water until a solid begins to separate.
• the mixture is cooled; the crude product is collected by filtration, and recrystallized from isopropyl alcohol.
• the product separates as yellow needles melting at 169170 (corr.) in a yield of 39 g. (73%).
• EXAMPLE V 4 -bis- 2 -hydroxyethyl amino-2 5 -n itro-Z-fruyl quinazoline (NF -1 088)
• NF -1 088 A 500 ml., three-neck flask, fitted with a stirrer, was charged with 30.2 g. (0.11 mole) of the compound of Example I, B., and 26.3 g. (0.25 mole) of diethanolamine in 300 ml. of dimethylformamide.
• the solution is heated on a steam bath for 2 hours.
• the solution is diluted with water until a solid begins to separate.
• the mixture is cooled and the crude product is collected by filtration and recrystallized from ethanol.
• the product separates as yellow platelets melting at 162.5164.5 (corr.) in a yield of 22 g. (58%).
• EXAMPLE VI 4 2 -hydr0xyethyl methylam in0-2- 5 -nitr0-2-furyl quinazoline (NF-1081 A mixture of 50 g. (0.182 mole) of the compound of Example I, B., and 34 g. (0.45 mole) of N-methylethanol- EXAMPLE VII 4-(Zanethoxyethyl)amino-2-(5-nitro-2-fulyl) quinazoline (NF-1175) A 2 1., three-neck flask, fitted with a stirrer, condenser, and a stopper, is charged with 40 g. (0.145 mole) of the compound of Example I, B., and 22.5 g.
• EXAMPLE VIII 4-(3-methoxypropylamino)2-(5-nitr0-2-furyl) quinazoline (NF-1145)
• a 1 1., three-neck flask, fitted with a stirrer, is charged with 35 g. (0.127 mole) of the compound of Example I, B., and 23.1 g. (0.26 mole) of methoxypropylamine in 500 ml. of dimethylformamide.
• the solution is heated on a steam bath for 2 hours.
• the solution is diluted with Water until a solid begins to separate.
• the mixture is cooled; the crude product is collected by filtration, and recrystallized from isopropyl alcohol.
• the product separates as yellow platelets melting at 143-145 (corr.) in a yield of 33 g. (82%).
• EXAMPLE IX 4 -bis( Z-ethoxyethyl am ino-Z 5 -nitr0-2 -fwyl quinazoline (NF-1127) A 2 l., three-neck flask, fitted with a stirrer, is charged with 35 g. (0.127 mole) of the compound of Example I, B., and 42 g. (0.26 mole) of diethoxyethylamine in 1 l. of dimethylformamide. The solution is heated on a steam bath, with stirring, for 2 hours. The solution is diluted with water until a solid begins to separate. The mixture is cooled; the crude product is collected by filtration, and recrystallized from isopropyl alcohol. The product separates as yellow needles melting at 6061 (corr.) in a yield of 40 g. (79%).
• a yellow solid is collected by filtration, slurried in.cold water and made basic with sodium hydroxide solution.
• the free base, melting at 164-166, is collected by filtration in a yield of 42 g. (100%). Recrystallization from ethanol gives the product as yellow platelets melting at 170-1715 (corn).
• the free base (40 g., 0.104 mole) is dissolved in 500 ml. of glacial acetic acid and anhydrous hydrogen chloride is bubbled into the solution until saturated. The mixture is cooled and diluted with anhydrous ether. A yellow solid is collected by filtration and recrystallized from ethanot to give the hydrochloride as a yellow solid melting at 211213 in a yield of 30 g. (63.5%).
• EXAMPLE XIV 4-[ (Z-hydroxyethyl) isopropylamino] -2-(5-nitr0-2-furyl) quinazoline (NF-1192 A 1 l., three-neck flask, fitted with a stirrer is charged with 35 g. (0.127 mole) of the compound of Example I, B., and 25 g. (0.242 mole) of N-isopropylethanolamine in 500 ml. of dimethylformamide. The solution is heated on a steam bath for 2 hours. The solution is diluted with water until a solid separates and the mixture is cooled. The product is collected by filtration and recrystallized from isopropyl alcohol. The product separates as yellow platelets melting at l48150 in a yield of 21 g. (48%).

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• Life Sciences & Earth Sciences (AREA)
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• General Health & Medical Sciences (AREA)
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• Plural Heterocyclic Compounds (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

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Citations (1)

• 1964
  • 1964-12-14 US US418311A patent/US3324122A/en not_active Expired - Lifetime
• 1965
  • 1965-09-23 IL IL24359A patent/IL24359A/xx unknown
  • 1965-10-08 ES ES0318292A patent/ES318292A1/es not_active Expired
  • 1965-10-13 DE DE19651620076 patent/DE1620076A1/de active Pending
  • 1965-10-15 SE SE13375/65A patent/SE325579B/xx unknown
  • 1965-10-20 DK DK535765AA patent/DK117902B/da unknown
  • 1965-10-21 NL NL6513634A patent/NL6513634A/xx unknown
  • 1965-11-15 AT AT1028165A patent/AT255424B/de active
  • 1965-11-16 NO NO160494A patent/NO118066B/no unknown
  • 1965-11-18 BE BE672504A patent/BE672504A/xx unknown
  • 1965-12-10 FR FR41816A patent/FR1460221A/fr not_active Expired
  • 1965-12-10 FR FR41817A patent/FR4910M/fr not_active Expired
  • 1965-12-13 CH CH1713065A patent/CH448110A/de unknown
  • 1965-12-13 GB GB52914/65A patent/GB1101179A/en not_active Expired
  • 1965-12-14 BR BR175667/65A patent/BR6575667D0/pt unknown

Patent Citations (1)

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