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
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
  • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
  • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
  • C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
• • 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
  • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
  • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
• • 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

Definitions

• This invention relates to novel chemical compounds useful in chemotherapy and more particularly it is concerned with certain novel benzimidazoles that are useful in altering blood pressure.
• nitroglycerin a compound for reducing blood pressure
• nicotinic alcohol derivatives a compound for reducing blood pressure
• reserpine a compound for reducing blood pressure
• priscoline a compound for reducing blood pressure
• ganglionic blocking agents a compound for reducing blood pressure.
• Nitroglycerin has the disadvantage of rapidly producing an effect which is not sustained; the nicotinic alcohol derivatives and reserpine are disadvantageous for a variety of reasons, and the ganglionic blocking agents are much too dangerous for use except under carefully supervised conditions, such as in a hospital.
• R represents an unsaturated short-chain aliphatic radical, for example allyl, methallyl, haloallyl, or crotyl, while R and R stand for identical or different aryl, aralkyl, heteroaryl, and heteroaralkyl radicals, which may be substituted in turn.
• X is a nontoxic anion. It will be understood that the benzene nucleus of the benzimidazole moiety may be substituted by one or more monovalent substituents such as halogen, alkyl, alkoxy, acylsulfono, sulfonoamido, nitro, or amino groups.
• esters of unsaturated aliphatic alcohols for instance, with esters of hydrohalic acids or esters of alkylsulfonic and arylsulfonic acids; or compounds of the type:
• the known 1-benZyl-2-phenylbenzimidazole may be reacted with allyl bromide and, furthermore, l-allyl-2 phenylben1imidaz'ole may be reacted with benzyl chloride.
• compounds of the type may be reacted with arylcarboxylic acids, aralkylcarbofylic acids, heteroarylcarboxylic acids, or heteroaralkylcarboxylic acids, or with reactive acid derivatives thereof followed by closure of the benzimidazole ring by conven tional methods.
• Example I Z-benzyl-benzimidazole is heated in the presence of an aliquot amount of sodium ethoxide with a small excess of crotyl chloride, the sodium chloride formed is removed by vacuum filtration, and the residue is evaporated, then dissolved and reprecipitated from dioxane to give 1-crotyl-2-benzyl-benzimidazole, melting at 205208 C. Administration of the product causes raising of the blood pressure.
• Example II Z-benzyl-benzimidazole is heated with slightly more than 2 moles of allyl bromide in the presence of 1 mole of sodium ethoxide, then the mixture is worked-up as described in Example I and the product is reprecipitated from methanol to give l,3-diallyl-2-benzyl-benzimidazolium chloride, melting at 277-278 C. Administration of the product causes raising of the blood pressure.
• Example III 1-(fi-methylallyl)-2-benzyl-benzimidazole is prepared from ,B-methylallyl chloride and 2-benzyl-benzimidazole by heating these reactants together with sodium ethoxide in a procedure according to Example I.
• the hydrochloride of this compound is found to melt at 118-120 0, following reprecipitation from acetone. This compound is heated for a short time under reflux with twice the stoichiometrical'ly equivalent amount of allyl bromide and, after boiling for about 1 hour, the liquid solidifies.
• Example IV 2-(a-hydroxybenzyl)-benzimidazole is heated for several hours with a small excess of crotyl chloride in the presence of the calculated amount of sodium ethoxide and the precipitated sodium chloride is filtered off under suction. 1 crotyl 2 (a hydroxybenzyl) benzimidazole crystallizes upon cooling and when it has been recrystallized from absolute alcohol, it melts at 162- 163 C. Administration of this product causes lowering of the blood pressure.
• Example V Example VI About 1 part by weight of 2-phenyl-1-benzyl-benzimidazole (melting point, 136l37 C.) is heated, under reflux, with 2 /2 parts by weight of allyl bromide. Precipitation of l-allyl-2-phenyl-3-benZyl-benzimidazolium bromide begins after a short time. Following evaporation of excess allyl bromide and redissolution in isopropyl alcohol, colorless crystals, melting at l84-l86 C., are obtained. Upon administration, this product causes a rise in blood pressure.
• Example VII Approximately equal parts by Weight of 1-allyl-2-(2'- furyl)-benzimidazole (which may be prepared according to Example V) and of 2-thienylmethyl chloride are heated together to about 100 C. for several hours. The mass begins to solidify in about 1 hour. Following rebenzimidazolium chloride.
• Example VIII Example IX Approximately equal parts by weight of 4-chlorobenzyl chloride and 1-al1yl-2-phenylbenzimidazole (melting point -96 C.), which may be prepared from Z-phenylbenzimidazole by the method according to Example V, are heated on a Water bath. During 1 hour, the entire mass solidifies in crystalline form. After grinding with ethyl acetate and reprecipitation from chloroform by addition of carbon tetrachloride, fine, colorless needles of 1 allyl 2 phenyl 3 (4' chlorobenzyl) benzimidazolium chloride, melting at 223-225 C. are obtained, which are very easily water-soluble. Upon ad ministration, this product causes a rise in blood pressure.
• a benzimidazolium compound selected from the group consisting of 1,3-diallyl-2-benzyl-benzirnidazolium bromide, 1 (fl methylallyl) 2 benzyl 3 allylbenzimidazolium chloride, 1 allyl-2-phenyl-3-benzyl-benzimidazolium bromide, l-allyl-2-(2'-furyl)-3-(2'-thienylmethyD-benzirnidazolium chloride and 1-allyl-2-phenyl- 3 2'-thienylmethyl -benzimid azolium chloride.

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

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Citations (1)

• 0
  • DE DENDAT1067026D patent/DE1067026B/de active Pending
• 1959
  • 1959-01-27 GB GB2957/59A patent/GB849793A/en not_active Expired
  • 1959-01-27 US US789239A patent/US2965647A/en not_active Expired - Lifetime

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