US3651094A - 2 3-dihydro-5-acylbenzofuran-2-carboxylic acids - Google Patents

2 3-dihydro-5-acylbenzofuran-2-carboxylic acids Download PDF

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US3651094A
US3651094A US827941A US3651094DA US3651094A US 3651094 A US3651094 A US 3651094A US 827941 A US827941 A US 827941A US 3651094D A US3651094D A US 3651094DA US 3651094 A US3651094 A US 3651094A
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dihydro
carboxylic acid
benzofuran
butyryl
acid
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Bernard Libis
Ernst Habicht
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Novartis Corp
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Geigy Chemical Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2

Definitions

  • the present invention relates to new heterocyclic carboxylic acids having valuable pharmacological properties. More particularly, the invention pertains to new 5-acyl benzofuran-Z-carboxylic acids, S-acyl-benzothiophene-Z- carboxylic acids and pharmaceutically acceptable salts thereof with bases which compounds exhibit anti-tussive and simultaneously diuretic and saluretic activities.
  • the present invention provides therapeutic compositions consisting essentially of (1) a S-acyl-benzofuran-Z-carboxylic acid or 5-acyl-benzothiophene-Z-carboxylic acid as aforesaid or a pharmaceutically acceptable salt thereof with a base and (2) a pharmaceutical carrier therefor.
  • the invention also provides methods for producing simultaneously diuretic and saluretic effects and inhibiting tussive irritation in mammals which comprise administering to said mammals, an eflective amount of a compound according to the invention or a pharmaceutically acceptable salt thereof with a base.
  • the present invention provides, in its broadest aspect, a compound of the Formula I wherein as well as pharmaceutically acceptable salts thereof with bases.
  • Z occupies the 4- or 6-position and Z the 6- and 7-position, and R is for example the ethyl,
  • propyl isopropyl, butyl, isobutyl, sec. butyl, tert. butyl, pentyl, isopentyl, l-methylbutyl, l-ethylpropyl, 1,1-dimethylpropyl, hexyl, isohexyl, peptyl, isopeptyl or 1,1-diethyl propyl group.
  • a preferred sub-class of compounds according to the instant invention are those having the Formula I illustrated above wherein R is alkyl having from 2 to 7 carbon atoms,
  • X is oxygen
  • Y and Y are hydrogen and Z and Z independently, are hydrogen or methyl as well as pharmaceutically acceptable salts thereof with bases.
  • Especially preferred compounds of Formula I are 2,3- dihydro-S-butyryl-6-methyl-benzofuran-Z-carboxylic acid, 2,3-dihydro-5-butyryl 6,7 dimethyl-benzofuran 2 carboxylic acid and 2,3-dihydro-5-(2-ethyl-butyryl)-6-methyl benzofuran-Z-carboxylic acid as Well as pharmaceutically acceptable salts thereof with bases.
  • the compounds of the present invention are prepared by reacting a compound of the Formula II or with a carboxylic acid anhydride of the Formula IV (III) wherein R has the meaning given under Formula I and Q is halogen,
  • Q is preferably chlorine or bromine.
  • Suitable catalysts for the reaction according to 'Friedel-Crafts are, e.g. especially aluminium chloride and tin(lV)-chlm ride, also zinc chloride, concentrated sulfuric acid, phosphoric acid, polyphosphoric acid or pyrophosphoric acid.
  • the stated acids are preferentially used where the acylation agent is a carboxylic acid anhydride.
  • the reaction is preferably performed in a solvent. Suitable solvents are, e.g.
  • aliphatic or cycloaliphatie hydrocarbons such as heptane or cyclohexane, nitrohydrocarbons such as nitromethane, nitrocyclohexane or nitrobenzene, or halogen hydrocarbons such as carbon tetrachloride, ethylene chloride, methylene chloride, o-dichlorobenzene and, moreover, carbon disulfide.
  • Suitable starting materials of the Formula II, wherein X is oxygen are, e.g. compounds of which the radicals 3 Y Y Z and Z correspond with groups listed under Formula I.
  • the 2,3-dihydro-benzofuran-Z-carboxylic acid [cp. R. Fittig and G. Ebert, AnmChem. 21-6, 116 (1883)] and the 2,3-dihydro-6-methoxybenzofuran-2-carboxylic acid [cp. W. Will and P. Beck, Chem. Ber. 19, 1783 (1886)] are, for example, known.
  • Further compounds of this series may be prepared e.g.
  • compounds of the Formula II can also be produced by reducing optionally substituted benzofuran-Z-carboxylic acids, e.g. with sodium amalgam, to obtain corresponding 2,3-dihydro benzofuran-Z-carboxylic acids.
  • optionally substituted benzofuran-Z-carboxylic acids e.g. with sodium amalgam
  • 2,3-dihydro benzofuran-Z-carboxylic acids e.g. with sodium amalgam
  • Substituted benzo[b]thiophene-2-carboxylic acids can also be obtained by condensation of ohalogen benzene aldehydes to the corresponding substituted 5-(o-halogen-benzyliden)-rhodanine and by boiling these with sodium hydroxide and if necessary heating with sodium methylate in dimethylene glycol at about .150l60 (cp. M. D. Castle, R. G. Plevey and Y. C.
  • the compounds of Formula I which are novel possess valuable pharmacological prop erties in conjunction with a high therapeutic index. They exhibit in particular, antitussive and diuretic activity.
  • the pharmocological activity of the compounds of the invention are determined in various standards tests with experimental animals. Thus antitussive activity is demonstrated by its inhibiting effect on induced tussive irritation in the cat, [cp. R. Domenjo z, Arch. exptl. Pathol. Pharmacol. 215, 19-24 (1952)]. After the intravenous administration, about 1 mg./kg.
  • the toxicity of the compounds of the invention on oral administration is of favourably low order.
  • the new compounds of the Formula I and their pharmaceutically acceptable salts with bases are thus suitable as medicaments which can be administered orally, rectally or parenterally for the relief of tussive irritation and for the production of diuretic and saluretic effects.
  • the pharmaceutically acceptable salts of the compounds of the invention may be prepared by any of the methods known in the art. To form the salts, it is possible to use inorganic or organic bases such as, e.g. alkali or alkalineearth metal hydroxides, carbonates or bicarbonates, triethanolamine or choline.
  • the daily dosages of free bases, or of pharmaceutically acceptable salts thereof vary between 1 and 20 mg./kg. per os for mammals. Suitable dosage units such as drage, capsules, tablets, suppositories or ampoules, preferably contain 25-250 mg. of an active substance, according to the invention, or of a pharmaceutically acceptable salt theerof.
  • Dosage units for oral administration preferably contain as active substance between 20% and of a compound of the Formula I, or of a pharmaceutically acceptable salt thereof. They are produced by combining the active substance, e.g. with solid, pulverulent carriers such as lactose, saccharose, sorbitol, mannitol; starches such as potato starch, maize starch or amylopectin, also laminaria powder or citrus pulp powder; cellulose derivatives or gelatine, optionally with the addition of lubricants, such as magnesium or calcium stearate or polyethylene glycols, to form tablets or drage cores. The latter are coated, e.g. with concentrated sugar solutions which can also contain, e.g.
  • suitable dosage units for oral administration are hard gelatine capsules as well as soft, closed capsules made of gelatine and a softener such as glycerin.
  • the hard capsules preferably contain the active substance as a granulate in admixture with lubricants such as talcum or magnesium stearate and, optionally, stabilisers, 'such as sodium metabisulphite or ascorbic acid.
  • the active substance is preferably dissolved or suspended in suitable liquids, such as liquid polyethylene glycols, whereby stabilisers can likewise be added.
  • sucking tablets e.g. sucking tablets
  • forms not administered as a single dosage e.g. cough syrup and cough drops prepared with the usual auxiliary agents.
  • Suitable dosage units for rectal administration are, e.g. suppositories consisting of a combination of a compound of the Formula I, or of a suitable salt thereof, with a neutral fatty foundation substance, or also gelatine rectal capsules containing a combination of the active substance with polyethylene glycols.
  • Ampoules for parenteral, especially intramuscular administration, and also intravenous administration preferably contain a water-soluble salt of a compound of the Formula I as active substance, in a concentration of preferably O.55%, optionally together with suitable stabilising agents and buffer substances, in an aqueous solution.
  • the present invention also provides a therapeutic composition consisting essentially of (1) a compound of the Formula I or a pharmaceutically acceptable salt thereof with a base and (2) a pharmaceutical carrier therefor.
  • the invention provides methods for producing a simultaneous diuretic and saluretic effect in mammals and for inhibiting tussive irritation in mammals which methods comprise administering to said mammal an effective amount of a compound of the Formula I or a pharmaceutically acceptable salt thereof with a base.
  • compositions and methods in the said compound of the Formula I R is alkyl having from 2 to 7 carbon atoms,
  • Y and Y are hydrogen and Z and Z independently, are hydrogen or methyl.
  • the preferred specific compound for the treatment of tussive irritation is 2,3-dihydro-5-butyryl-6-rnethyl-benzofuran 2 carboxylic acid.
  • 2,3-dihydro-5-butyryl- 6,7 dimethylbenzofuran 2 carboxylic acid and 2,3- dihydro 5 (2 ethyl-butyryl)-6-methyl-benzofuran-2- carboxylic acid are preferred.
  • EXAMPLE 1 (a) 25.2 g. of 2,3-clihydro-6-methylbenzofuran-2-carboxylic acid are slurried with 135 ml. of nitrobenzene and, while stirring and cooling, 69.5 g. of aluminium chloride are added in portions and within 30 minutes, so that the temperature does not rise above 10. At the same temperature, 22.3 g. of butyryl chloride are added dropwise within 30 minutes. The reaction mixture is then further stirred for 5 hours in a nice bath, allowed to stand for 16 hours at room temperature, heated for a further hour to 40 and then poured on to 500.0 g. of ice. To the obtained suspension are added 50 ml. of concentrated hydrochloric acid.
  • the reaction mixture is extracted three times with, each time, 150 ml. of ether.
  • the ether extract is dried over sodium sulfate and concentrated by evaporation.
  • the residue is slurried in hexane, shaken up, again separated from the hexane and recrystallised from ben zene.
  • the obtained 2,3dihydro-5-butyryl-G-methylbenzofuran 2 carboxylic acid melts at 140l41.
  • the starting compound of (a) is produced as follows:
  • the starting compound is produced as follows:
  • the ether solution is dried over sodium sulfate and concentrated by evaporation.
  • the residue is recrystallised from carbon tetrachloride/benzene, whereupon the 2,3 dihydro-7-chlorobenzofuran-Z- carboxylic acid melts at 146.
  • EXAMPLE 4 (a) The 2,3 dihydro-5-butyryl-6-chlorobenzofuran-2- carboxylic acid, M.P. 110 (from benzene) is produced, analogously to Example 1(a), from the 2,3-dihydro-6- chlorobenzofuran-2-carboxylic acid with butyryl chloride in the presence of aluminium chloride in nitrobenzene.
  • the starting compound, 2,3-clihydro-7-methoxy-benzofurane-Z-carboxylic acid is produced as follows:
  • the starting compound is produced as in Example 1(b).
  • EXAMPLE 8 (a) Analogously to Example 1(a), the 2,3-dihydro- 6,7-dimethyl-benzofuran-Z-carboxylic acid is acylated with butyryl chloride in the presence of aluminum chloride and in nitrobenzene to the 2,3-dihydro-5-butyryl-6,7- dimethyl-benzofuran-Z-carboxylic acid, M.P. 148 (from ethyl acetate).
  • the starting compound, 2,3-dihydro-6,7-dimethyl-benzofuran 2-carboxylic is produced as follows:
  • the mixture was stirred for 30 minutes at 40 and 30 minutes at 80 and then poured into 2 litres of ice water.
  • the aqueous alkaline solution was washed twice with about 400 ml. of ether and acidified to a pH of 2-3 with concentrated hydrochloric acid.
  • the suspension obtained was stirred for one half hour at room temperature.
  • the crystalline precipitate formed was collected by filter under suction and recrystallised from ethanol.
  • the starting compound is produced as in Example 1(b) EXAMPLE 10
  • the 2,3-dihydro-3,6-dimethylbenzofuran-Z-carboxylic acid [cf. Fries, Finkewirth, A. 362, 52] is acylated with butyryl chloride in nitrobenzene in the presence of aluminum chloride to the 2,3 dihydro 3,6 dimethyl-5-butyryl-benzofuran-Z-carboxylic acid, M.P'. 98-100" (from benzene).
  • the starting compound is produced as in Example 1(b).
  • EXAMPLE 12 (a) Analogously to Example 1(a), the 2,3-dihydro-6 methyl-benzofuran-2-carboxylic acid is acylated with hexanoyl chloride in nitrobenzene in the presence of aluminum chloride to the 2,3-dihydro-5-hexanoyl-6-methylbenzofuran-Z-carboxylic acid, M.P. 137 (from cyclohexane/ ethyl acetate).
  • the starting compound is produced as in Example 1(b).
  • the starting compound, 2,3-dihydro-6-ethyl-benzofuran- 2-carboxylic acid is produced as follows:
  • the aqueous, alkaline solution is washed twice with 300 ml. of ether each time, acidified with concentrated hydrochloric acid to pH 2-3 and the precipitated crude product is filtered oil under suction.
  • the crude product is recrystallised from ethanol and dried in vacuo at 80 whereupon the 6-ethyl-benzofuran- 2-carboxylic acid obtained melts at l52l54.
  • EXAMPLE 14 (a) Analogously to Example 1(a), the 2,3-dihydrofluoro-benzofuran-Z-carboxylic acid is acylated with butyryl chloride in nitrobenzene in the presence of aluminum chloride to the 2,3-dihydro-5-butyryl-6-fluoro-benzofuran-Z-carboxylic acid, M.P 144 (from cyclohexane/ ethyl acetate).
  • the starting compound, 2,3-dihydro-6-fluoro-benzofuran-Z-carboxylic acid is produced as follows:
  • the starting acid is produced as follows:
  • EXAMPLE 18 (a) Analogously to Example 1(a), the 2,3-dihydro-4- chloro-benzo[b] thiophene 2 carboxylic acid is acylated with butyryl chloride to the 2,3 dihydro-4-chloro-5-butyryl-benzo[b]thiophene-2 carboxylic acid, M.P. 178 (from methanol).
  • the starting compound is produced as follows:
  • the starting compound is produced as follows:
  • EXAMPLE 20 12.6 g. of the 2,3 dihydro-6-methylbenzofuran-2-carboxylic acid are dissolved in 70 ml. nitrobenzene and during 30 minutes with stirring and cooling are added 35 g. aluminium chloride in portions. The temperature must be maintained under 10. At the same temperature, 16 g. butyryl bromide are dropped in during 30 minutes.
  • reaction mixture is then further stirred for hours in an ice bath, allowed to stand for 16 hours at room temperature, heated for a further hour to 40 and then poured on to 500 g. of ice.
  • 50 ml. of concentrated hydrochloric acid To the obtained suspension are added 50 ml. of concentrated hydrochloric acid.
  • the reaction mixture is extracted three times with, each time, 150 ml. of ether.
  • the ether extract is dried over sodium sulphate and concentrated by evaporation.
  • the residue is slurried in hexane, shaken up, again separated from the hexane and recrystallised from benzene.
  • the obtained 2,3- dihydro 5 butyryl-methylbenzofuran-2-carboxylic acid melts at 140-l41.
  • EXAMPLE 21 12.6 g. of 2,3-dihydro-6-methylbenzofuran-Z-carboxylic acid are dissolved in 70 m1. nitro benzene and 35 g. aluminium chloride are added in portions during 30 minutes with stirring and cooling. The temperature must be maintained at below At the same temperature, 16.5 g. butyric acid anhydride is dropped in during 30 minutes.
  • reaction mixture is then further stirred for 5 hours in an ice bath, allowed to stand for 16 hours at room temperature, heated for a further hour to 40 and then poured onto 500 g. of ice.
  • 50 ml. of concentrated hydrochloric acid To the obtained suspension are added 50 ml. of concentrated hydrochloric acid.
  • the reaction mixture is extracted three times with, each time, 150 m1. of ether.
  • the ether extract is dried over sodium sulphate and concentrated by evaporation. The residue is slurried in hexane, shaken up, again separated from the hexane and recrystallised from benzene.
  • EXAMPLE 23 1000 g. of 2,3-dihydro-S-butyryl-G-methyl-benzofuran- 2-carboxylic acid are mixed with 550 g. of lactose and 292 g. of potato starch. The mixture is moistened with an aqueous solution of 8 g. of gelatine and granulated through a sieve. After drying, 60 g. of potato starch, 60 g. of talcum, 10 g. of magnesium stearate and 20 g. of colloidal silicon dioxide are mixed in.
  • the mixture is pressed into 10,000 tablets each weighing 200 mg. and each containing 100 mg. of active substance.
  • the tablets can be provided with grooves for a more accurate adjustment of the dosage amount.
  • active substance the same amount of S-butyryl-2,3-dihydro-6,7-dimethyl-benzofuran-2-carboxylic acid can also be used.
  • EXAMPLE 24 A granulate is produced from 1000 g. of 2,3-dihydro-5- butyryl-G-methylbenzofuran 2 carboxylic acid, 379 g. of lactose and the aqueous solution of 6 g. of gelatine. After drying, the granulate is mixed with 10 g. of colloidal silicon dioxide, 40 g. of talcum, 60 g. of potato starch and 5 g. of magnesium stearate and the mixture pressed into 10,000 drages cores. These are subsequently coated with a concentrated syrup made from 533.5 g. of crystallised saccharose, 20 g. of shellac, 75 g. of gum arabic, 250 g. of talcum, 20 g. of colloidal silicon dioxide and 1.5 g. of dyestufr', and dried. The obtained drages each weigh 240 mg. and each contain 100 mg. of active substance.
  • EXAMPLE 25 100 g. of 2,3-dihydro-5-butyryl-6-methylbenzofuran-2- carboxylic acid are mixed with 9.5 g. of talcum and 0.5 g. of magnesium stearate and the mixture is put through a sieve (e.g. Sieve IV, Ph, Helv. V). Capsules of size 0 are then filled from the mixture. In this way' 1000 capsules each containing mg. of active substance are produced. As active substance can also be used the same amount of 5-butyryl-2,3-dihydro 6,7 dimethyl-benzofuran-2-carboxylic acid.
  • EXAMPLE 26 1.5 litres of glycerin, 42 g. of p-hydroxy-benzoic acid methyl ester, 18 g. of p-hydroxybenzoic acid propyl ester and, while heating slightly, 50 g. of 2,3-dihydro-5-butyryl- 6-methylbenzofuran-Z-carboxylic acid are dissolved in 3 litres of distilled water. To this are added 4 litres of 70% sorbitol solution. 1000 g. of crystallised saccharose, 350 g. of glucose and an aromatic, e.g. 250 g. of Orange Peel Soluble Fluid of Eli Lilly and Co., Indianapolis, or 5 g. of natural lemon aroma and 5 g.
  • EXAMPLE 27 To prepare cough drops having an active substance content of 2.5%, 250 g. of 2,3-dihydro-5-butyryl-6-methylbenzofuran-2-carboxylic acid and 30 g. of sodium cyclamate are dissolved in a mixture of 4 litres of ethanol (96%) and 1 litre of propylene glycol. At the same time, 3.5 litres of 70% sorbitol solution are mixed with 1 litre of water and the mixture is added to the above active substance solution. An aromatic is then added, e.g. 5 g. of cough-drop aroma or 30 g. of Grapefruit Essence, both 13 from the firm Haarmann und Reimer, Holzminden, Germany. The whole is well mixed, filtered and made up to 10 litres with distilled water.
  • EXAMPLE 28 A suppository mixture is prepared from 2.5 g. of 2,3- dihydro-S-butyryl 6 methylbenzofuran-Z-carboxylic acid and 167.5 g. of adeps solidus. From the mixture are poured 100 suppositories each containing 25 mg. of active substance.
  • R is alkyl having from 2 to 7 carbon atoms
  • Y and Y are hydrogen and Z and Z independently, are hydrogen or methyl and pharmaceutically acceptable salts thereof with bases.
  • a compound according to claim 1 which is 2,3-dihydro-S-butyryl 6 methyl-benzofuran-Z-carboxylic acid and pharmaceutically acceptable salts thereof with bases.
  • a compound according to claim 1 which is 2,3-dihydro-S-butyryl-6,7-dimethyl-benzofuran 2 carboxylic acid and pharmaceutically acceptable salts thereof with bases.
  • a compound according to claim 1 which is 2,3-di hydro-S-(Z-ethyl-butyryl) 6 methyl benzofuran-Z-carboxylic acid and pharmaceutically acceptable salts thereof with bases.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Furan Compounds (AREA)
US827941A 1968-05-30 1969-05-26 2 3-dihydro-5-acylbenzofuran-2-carboxylic acids Expired - Lifetime US3651094A (en)

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3954748A (en) * 1968-07-29 1976-05-04 Societe D'etudes Scientifiques Et Industrielles De L'ile-De-France 3-Alkoxy-thianapthene-2-carboxamides
US4087542A (en) * 1975-07-09 1978-05-02 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids
US4181727A (en) * 1975-07-09 1980-01-01 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids
US4213999A (en) * 1979-06-07 1980-07-22 Shell Oil Company Inhibition of lipogenesis
US4213998A (en) * 1979-06-07 1980-07-22 Shell Oil Company Inhibition of lipogenesis
US4296122A (en) * 1975-07-09 1981-10-20 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-(acyl)benzofuran-2-carboxylic acids
US4401669A (en) * 1978-01-27 1983-08-30 Merck & Co., Inc. 2,3-Dihydro-substituted-5-benzoyl benzofuran-2-carboxylic acids and their use in treating hypertension
US4654365A (en) * 1985-09-26 1987-03-31 Merck & Co., Inc. 2,3-dihydro-5-(3-oxo-2-cyclohexen-1-yl)-2-benzofurancarboxylic acids, and their salts useful in the treatment of brain injury
US4822803A (en) * 1983-10-31 1989-04-18 Merck Frosst Canada, Inc. Benzofuran 2-carboxylic acid hydrazides useful as inhibitors of leukotriene biosynthesis
US4933351A (en) * 1983-10-31 1990-06-12 Merck Frosst Canada, Inc. Benzofuran 2-carbox amides useful as inhibitors of leukoriene biosynthesis
US20040071797A1 (en) * 2002-10-09 2004-04-15 Dennis Donald P. Method and formulation for suppressing mold

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Publication number Priority date Publication date Assignee Title
USB353986I5 (enrdf_load_stackoverflow) * 1969-10-10 1975-01-28
US3969529A (en) * 1969-10-10 1976-07-13 C.E.R.P.H.A. Phenoxyacetic acid derivatives as diuretic agents
US4237144A (en) * 1979-06-21 1980-12-02 Merck & Co., Inc. 2,3-Dihydro-2,6,7-trisubstituted-5-acylbenzofurans
US4552891A (en) * 1983-09-13 1985-11-12 Eli Lilly And Company Benzothiophene derivatives
US5760062A (en) * 1995-04-18 1998-06-02 Geron Corporation Telomerase inhibitors
US5703116A (en) * 1995-04-18 1997-12-30 Geron Corporation Telomerase Inhibitors
US5863936A (en) * 1995-04-18 1999-01-26 Geron Corporation Telomerase inhibitors
US5770613A (en) * 1995-09-29 1998-06-23 Geron Corporation Telomerase inhibitors
US5767278A (en) * 1995-10-06 1998-06-16 Geron Corporation Telomerase inhibitors

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Cited By (12)

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US3954748A (en) * 1968-07-29 1976-05-04 Societe D'etudes Scientifiques Et Industrielles De L'ile-De-France 3-Alkoxy-thianapthene-2-carboxamides
US4087542A (en) * 1975-07-09 1978-05-02 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids
US4163794A (en) * 1975-07-09 1979-08-07 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-furoyl benzofuran-2-carboxylic acids
US4181727A (en) * 1975-07-09 1980-01-01 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids
US4296122A (en) * 1975-07-09 1981-10-20 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-(acyl)benzofuran-2-carboxylic acids
US4401669A (en) * 1978-01-27 1983-08-30 Merck & Co., Inc. 2,3-Dihydro-substituted-5-benzoyl benzofuran-2-carboxylic acids and their use in treating hypertension
US4213999A (en) * 1979-06-07 1980-07-22 Shell Oil Company Inhibition of lipogenesis
US4213998A (en) * 1979-06-07 1980-07-22 Shell Oil Company Inhibition of lipogenesis
US4822803A (en) * 1983-10-31 1989-04-18 Merck Frosst Canada, Inc. Benzofuran 2-carboxylic acid hydrazides useful as inhibitors of leukotriene biosynthesis
US4933351A (en) * 1983-10-31 1990-06-12 Merck Frosst Canada, Inc. Benzofuran 2-carbox amides useful as inhibitors of leukoriene biosynthesis
US4654365A (en) * 1985-09-26 1987-03-31 Merck & Co., Inc. 2,3-dihydro-5-(3-oxo-2-cyclohexen-1-yl)-2-benzofurancarboxylic acids, and their salts useful in the treatment of brain injury
US20040071797A1 (en) * 2002-10-09 2004-04-15 Dennis Donald P. Method and formulation for suppressing mold

Also Published As

Publication number Publication date
NO122753B (enrdf_load_stackoverflow) 1971-08-09
CH508615A (de) 1971-06-15
SE360359B (enrdf_load_stackoverflow) 1973-09-24
NL6907966A (enrdf_load_stackoverflow) 1969-12-02
ES367837A1 (es) 1971-12-01
BE733768A (enrdf_load_stackoverflow) 1969-12-01
US3751430A (en) 1973-08-07
GB1265882A (enrdf_load_stackoverflow) 1972-03-08
DK124129B (da) 1972-09-18
DE1927393A1 (de) 1969-12-04
IE33124L (en) 1969-11-30
IE33124B1 (en) 1974-03-20
FR2009652A1 (enrdf_load_stackoverflow) 1970-02-06
IL32310A0 (en) 1969-07-30
AT284835B (de) 1970-09-25
IL32310A (en) 1972-12-29

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