US3681365A - Derivatives of acetic acid - Google Patents

Derivatives of acetic acid Download PDF

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Publication number
US3681365A
US3681365A US768881A US3681365DA US3681365A US 3681365 A US3681365 A US 3681365A US 768881 A US768881 A US 768881A US 3681365D A US3681365D A US 3681365DA US 3681365 A US3681365 A US 3681365A
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Prior art keywords
acetic acid
ester
mixture
piperidyl
ethyl
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Rudolf G Griot
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Sandoz AG
Sandoz Wander Inc
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Sandoz AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
    • C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
    • C07C59/70—Ethers of hydroxy-acetic acid, e.g. substitutes on the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4

Definitions

  • This invention relates to derivatives of acetic acid.
  • the invention pertains to bis-(substituted phenoxy) acetic acids and derivatives thereof which possess hypocholesteremic/hypolipemic activity.
  • the invention further relates to pharmaceutical compositions containing the above compounds as anactive ingredient thereof and the use of such compositions for the treatment of hypercholesteremia/hyperlipemia.
  • the compounds of the present invention are of the structural formula wherein R represents hydrogen or the residue of a monohydric alcohol capable of forming an ester by reaction with an acid,
  • a saturated aliphatic alcohol preferably a saturated lower aliphatic alcohol such as aliphatic alcohol having 1-5 carbon atoms, e.g. methanol, ethanol, propanol, isopropanol, butanol and the like;.an unsaturated aliphatic alcohol such as alkyl alcohol; a substituted aliphatic alcohol such as ethanolamine; an aromatic alcohol other than a phenol such as 'benzyl or phenylethylalcohol; an alicyclic alcohol such as cyclohexanol; a heterocyclic alcohol such as furfuryl alcohol an alcohol of the formula B-Ol-l where B represents piperidino, cyanomethyl or di[carb(lower)alkoxymethyl, where lower qualifies the alkoxy moiety to mean one containing l-S carbon atoms, an alcohol of the formula A-Ol-l wherein A (the point of attachment being at either the 2- of 3- positions);
  • each R independently, represents hydrogen or lower alkyl, preferably containing from one to four carbon atoms, e.g., methyl, ethyl, propyl and butyl;
  • R represents hydrogen; halo, preferably bromo or chloro; or lower alkyl, preferably containing from one to four carbon atoms, e.g., methyl, ethyl, propyl and butyl; R represents lower alkyl, preferably containing from one to four carbon atoms, e.g., methyl, ethyl, propyl and butyl; propargyl; phenyl; halophenyl, the halo substitutent preferably being bromo or chloro; or phenyl(lower)alkyl, the lower alkyl substituent preferably containing from one to four carbon atoms, e.g., benzyl and phenethyl;
  • R represents hydrogen; lower alkyl, preferably containing from one to four carbon atoms, e.g., methyl, ethyl, propyl and butyl; cycloalkyl containing from five to seven ring carbon atoms, e.g., cyclopentyl, cyclohexyl and cycloheptyl; phenyl; phenyl(lower) alky1, the lower alkyl substituent preferably containing from one to four carbon atoms, e.g., benzyl and phenethyl; lnaphthyl; or Z-naphthyl; and R represents lower alkyl, preferably containing from one to four carbon atoms, e.g., methyl, ethyl, propyl and butyl; cycloalkyl containing from five to seven ring carbon atoms, e.g., cyclopentyl, cyclohexyl and cycl
  • R R R and R each independently, represents hydrogen, chloro, iodo or bromo, and
  • R and R each additionally, independently, represents trifluoromethyl or phenyl (which term for purposes of the definition of the compounds of formula (I) in the specification and in the claims is also intended to include p-chlorophenyl, p-iodophenyl and pbromophenyl), provided 1. at least one of the R, and r is other than hydrogen,
  • R R R and R each, independently, may represent only chloro or hydrogen only when R represents other than hydrogen, a residue of a saturated aliphatic alcohol, the basic radical A defined above, piperidino, cyanomethyl or di[carb(lower)alkoxy]methyl,
  • R R R and R each, independently, represents only hydrogen, chloro, iodo or bromo, provided at least one represents other than chloro, only when R represents other than hydrogen or a residue of a saturated aliphatic alcohol,
  • R and R each, independently, represents trifluorornethyl or phenyl only a. when at least one of R R R and R represents chloro, fluoro or iodo,
  • R represents a trifluorornethyl or phenyl group and the other of 5 R, and R represents the second group, or
  • R represents other than hydrogen, A as defined above, or the residue of a saturated aliphatic alcohol.
  • residue of a monohydric alcohol is meant that moiety of the alcoho] other than the -OH portion.
  • l-lower alkyl-4-piperidyl e.g., l-methyl-4-piperidyl and l-ethyl4-piperidyl
  • l-lower alkyl-3-piperidyl e.g., --methyl-3-piperidyl and l-ethyl-3-piperidyl
  • l-lower aIkyl-Z-piperidyl e.g, l-methyl-Z-piperidyl and lethyI-Z-piperidyl
  • l-phenyl-4-piperidyl l-phenyl-3- piperidyl
  • l-phenyl-Z-piperidyl l-benzyl-4-piperidyl
  • l phenethyl-4-piperidyl i phenethyl-3-piperidyl
  • the compounds of formula (I) may be prepared according to the processes indicated below.
  • Method A pertains to the reaction of a substituted phenoxy halo acetic acid derivative (II) and an ap intestinaltely substituted phenol (lil) as the phenolate.
  • This reaction is conveniently effected in a suitable inert organic solvent such as dimethylacetamide; diethylacetamide; dimethylforrnamide; and tetramethylurea.
  • a suitable inert organic solvent such as dimethylacetamide; diethylacetamide; dimethylforrnamide; and tetramethylurea.
  • the reaction is initially carried out at room temperature and then allowed to continue at elevated temperatures up to about 80C.
  • the particular solvent employed is not critical, nor is the temperature employed critical provided it does not exceed about 80C.
  • the resulting acetic acid derivative (I) is readily recovered employing conventional techniques.
  • the substituted phenol (III) is converted to the phenolate using standard techniques, such as treating the phenol with either a strong alkali metal hydroxide, e.g., KOH or NaOH, and water or sodium hydride in dimethylacetamide.
  • a strong alkali metal hydroxide e.g., KOH or NaOH
  • Method B involves the reaction of the substituted phenol (IV) as a phenolate and a dihalocarboxylic acid or derivative thereof (V) and the solvents and temperatures which may be used are substantially as discussed with respect to method A.
  • the compounds (I) where R represents the basic radical A earlier described may be preferably obtained by treating the compounds of formula (I) where R H or lower alkyl with an alcohol A OH, where A is as earlier defined, under conventional transesterification conditions.
  • this procedure may be performed in an inert organic solvent such as benzene, toluene or xylene, in the presence of an alkali metal alkoxide, preferably sodium methoxide or ethoxide, at a temperature of about 50l50C, preferably at reflux temperature.
  • the compounds of formula (I) where R represents piperidino are preferably prepared from the acid halide of the compounds (I) by treatment with l-hydroxypiperidine or an appropriate salt thereof in inert solvent, e.g., benzene or toluene, at about room temperature.
  • inert solvent e.g., benzene or toluene
  • R represents cyanomethyl or di[carb(lower)alkoxy] methyl
  • the free acid is treated with a haloacetonitrile or a dialkylhalomalonate, respectively, in inert solvent such as tetrahydrofuran or ethyl acetate in the presence of a tertiary amine such as triethylamine, preferably at the reflux temperature of the system.
  • the substituted phenoxy haloacetic acid ester starting materials (ll) used for process A described above may be prepared as indicated according to processes C and D.
  • Method C concerns treatment of the phenolate of compound (IV) with a monohaloacetic acid (VI), e.g., chloro acetic acid, to obtain the substituted phenoxy acetic acid of formula (VII).
  • VI monohaloacetic acid
  • the same solvents and reaction conditions discussed respecting processes A and B apply here as well.
  • the compounds of formula (VII) are then halogenated to provide the compounds of formula (ll) (method D). Conventional halogenating agents such as bromine or chlorine may be employed.
  • the halogenation is conveniently carried out in a suitable inert organic solvent such as a halocarbon, for instance a chloralkane, e.g., dichloromethane, chloroform, carbontetrachloride, and the like.
  • a suitable inert organic solvent such as a halocarbon, for instance a chloralkane, e.g., dichloromethane, chloroform, carbontetrachloride, and the like.
  • a suitable inert organic solvent such as a halocarbon, for instance a chloralkane, e.g., dichloromethane, chloroform, carbontetrachloride, and the like.
  • a halocarbon for instance a chloralkane, e.g., dichloromethane, chloroform, carbontetrachloride, and the like.
  • the reaction is initially carried out at room temperature and then allowed to continue at reflux temperature.
  • neither the choice of solvent nor the temperature used is critical
  • the compounds of formula (I) are useful because they possess pharmacological properties in animals.
  • these compounds are useful as hypocholesteremics/hypolipemics, as indicated by activity in sodium hexobarbital anesthetized rat tested by extracting serum or plasma with isopropanol and noting the cholesterol content.
  • the compounds may be administered orally as such or admixed with conventional pharmaceutical carriers or administered orally in such forms as tablets, dispersible powders, granules, capsules, syrups and elixirs.
  • compositions may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions, and such compositions may contain one or more conventional adjuvants, such as sweetening agents, flavoring agents, coloring agents and preserving agents, in order to provide an elegant and palatable preparation.
  • adjuvants such as sweetening agents, flavoring agents, coloring agents and preserving agents
  • Tablets may contain the active ingredient in admixture with conventional pharmaceutical excipients, e.g., inert diluents, such as calcium carbonate, sodium carbonate, lactose and talc, granulating and disintegrating agents, e.g., starch and alginic acid, binding agents, e.g., starch, gelatin and acacia, and lubricating agents, e.g., magnesium stearate, stearic acid and talc.
  • the tablets may be uncoated or coated by known techniques to delay disintegration and adsorption in the gastro-intestinal tract and thereby provide a sustained action over a longer period.
  • suspensions, syrups and elixirs may contain the active ingredient in admixture with any of the conventional excipients utilized for the preparation of such compositions, e.g., suspending agents (methylcellulose, tragacanth and sodium alginate), wetting agents (lecithin, polyoxyethylene stearate and polyoxyethylene sorbitan monooleate) and preservatives (ethyl-p 'hydroxybenzoate).
  • suspending agents methylcellulose, tragacanth and sodium alginate
  • wetting agents lecithin, polyoxyethylene stearate and polyoxyethylene sorbitan monooleate
  • preservatives ethyl-p 'hydroxybenzoate
  • Capsules may contain the active ingredient alone or admixed with an inert solid diluent, e.g., calcium carbonate, calcium phosphate and kaolin.
  • the compounds of formula (I) where R H may also be utilized as hypocholesteremics/hypolipemics in the form of non-toxic pharmaceutically acceptable salts thereof.
  • the aluminum salt more specifically, that aluminum salt wherein two hydroxyl groups of Al(OH) have been replaced by the acid radical; non-toxic alkali metal salts, e.g., potassium and sodium salts; non-toxic alkaline earth metal salts, e.g., magnesium and calcium salts; salts with N-containing bases such as ammonium salts and pharmaceutically acceptable primary, secondary and tertiary amine salts, e.g., ethanol amine salts, diethanol amine salts, and the like.
  • the compounds (I) are basic esters, such as when R represents A as defined above, the compounds may also be used as the non-toxic acid addition salt thereof or quaternary salts.
  • the salts are prepared using conventional techniques.
  • the dosage of active ingredient employed for the alleviation of hyperlipemia may vary depending on the particular compound employed and the severity of the condition being treated. In general, satisfactory results are obtained when these compounds are administered at a daily dosage of from about 0.5 milligrams to about 50 milligrams per kilogram of animal body weight. This daily dosage is preferably given in divided doses and administered two to four times a day, or in sustained release form. For most large mammals, the total daily dosage is from about 50-2000 mg, and dosage forms suitable for internal use comprise from about 12.5 milligrams to about 500 milligrams of active compound in intimate admixture with a solid or liquid pharmaceutically acceptable carrier or diluent.
  • the preferred pharmaceutical compositions from the standpoint of preparation and ease of administration are solid compositions, particularly hard-filled capsules and tablets containing from 25 milligrams to about 250 milligrams of the active ingredient.
  • EXAMPLE 1 (p-trifluoromethylphenoxy)-(p-chlorophenoxy)acetic acid, ester with l-hydroxypiperidine
  • a mixture of 20.2 g. of l-hydroxypiperidine and 800 ml. of absolute diethyl ether is stirred and cooled to about C. in an ice-salt bath.
  • To the cooled mixture is then added dropwise with stirring a solution of 33 g. of (p-trifluoromethylphenoxy-(p-chlorophenoxy) acetyl chloride in 400 ml. of absolute diethyl ether, while maintaining the temperature of the reaction mixture between to 0C. with external cooling.
  • EXAMPLE 2 acid CIICOOCIIzCN A mixture of 50 g. of (p-biphenylyloxy)-(pchlorophenoxy) acetic acid, 24.2 g. of triethylamine and 18 g. of chloroacetonitrile and 240 ml. of ethyl acetate is refluxed on a steam bath for 24 hours, then filtered and the ethyl acetate solution extracted once with 500 ml. of water and then twice with 500 ml. (each) of 2N hydrochloric acid. The ethyl acetate layer is then dried over sodium carbonate, filtered with charcoal and then evaporated.
  • EXAMPLE 3 (p-iodophenoxy)-(p-chlorophenoxy)acetic acid dicarbethoxymethyl ester A mixture of 50 g. of (p-iodophenoxy)-(pchlorophenoxy) acetic acid, 24.2 g. of triethyiamine, 57.3 g. of diethylbromomalonate and 240 ml. of ethyl acetate is refluxed on a steam bath for 24 hours, then filtered and the ethyl acetate solution extracted once with 500 ml. of water and then twice with 500 ml. of 2N hydrochloric acid.
  • Step 1 (p-bromophenoxy)-( acetic acid methyl ester Sodium hydride (56.7 percent in mineral oil) (47 g.) is washed free from the mineral oil with low boiling petroleum either and suspended in 750 ml. of dimethylacetamide. To the suspension is added g. of p-bromophenol in 500 ml. of dimethylacetamide as the temperature is maintained at l0-20C. The mixture is stirred for 2 hours and methyl chloro acetate is added. The resulting mixture is stirred for 5 hours at 80 C. and then at room temperature for 72 hours. The resulting mixture is then poured over 2 liters of ice water, extracted with 750 ml. of isopropyl ether.
  • Step 2 a-bromophenoxy acetic acid methyl ester
  • l80 g. of (p-bromophenoxy)acetic acid methyl ester To 1 liter of carbon tetrachloride is added l80 g. of (p-bromophenoxy)acetic acid methyl ester. With stirring at room temperature bromine g.) is added dropwise and the mixture is stirred for l7 hours at room temperature. The mixture is washed with 1,500 ml. of water and then 500 ml. of cold lpercent aqueous sodium bicarbonate.
  • Step 3 (p-bromophenoxy)-(2-chloro-4- trifluoromethylphenoxy acetic acid methyl ester
  • dimethylacetamide 15 g. of 2- ehloro-4-trifluoromethylphenol
  • the resulting mixture is added dropwise, with stirring, to a suspension of 4.6 g. of 56.7 percent sodium hydride (which had been washed free of mineral oil with petroleum ether) in 100 ml. of dimethylacetamide.
  • the resulting mixture is stirred at room temperature for 90 minutes and 26 g.
  • Step B Preparation of bis-(p-bromophenoxy)acetic acid l-methyl-4-piperidyl ester
  • Bis-(p-bromophenoxy)acetic acid methyl ester 10 grams, is mixed with 10 grams of B-hydropyethylpiperidine, 50 mg. of sodium methoxide and 10 ml. of toluene.
  • the resulting mixture is then slowly heated to distill very slowly through a Vigreux column. When the temperature at the distilling head reaches 1 10C., the reaction mixture is cooled to 65C. and then evaporated on a rotary evaporator employing 12 mm. vacuum and maintaining the temperature between 657OC.
  • the crude product thus obtained is treated with an excess of a 20 percent aqueous solution of tartaric acid to yield the tartrate salt of bis-(pbromophenoxy)acetic acid ,B-piperidinoethyl ester.
  • the free base is obtained by treating the washed tartrate salt with 2N sodium hydroxide and extracting the base with dichloromethane.
  • the dichloromethane extract is dried over magnesium sulfate, the solvent evaporated and the residue neutralized with an isopropanolic solution of hydrogen chloride (10 percent hydrogen chloride gas in isopropyl alcohol).
  • Step 1 (p-trifluorornethylphenoxy)acetic acid Sodium hydride (56.7 percent in mineral oil) (47 g.) is washed free from the mineral oil with low boiling petroleum ether and suspended in 750 ml. of dimethylacetamide. To the suspension is added 81 g. of trifluoromethylphenol in 500 ml. of dimethylacetamide as the temperature is maintained at l0-20C. The mixture is stirred for 1 hour and 38 g. of chloroacetic acid is added. The resulting mixture is stirred for 5 hours at C. and then at room temperature for 72 hours.
  • Step 2 a-bromo-p-trifluoromethylphenoxy acetic acid.
  • Step 3 (p-trifluoromethylphenoxy)-(2,4- dichlorophenoxy)acetic acid
  • dimethylacetamide To 200 ml. of dimethylacetamide is added 16.3 g. of 2,4-dichlorophenol and the resulting mixture is added dropwise, with stirring, to a suspension of 9.2 g. of 56.7 percent sodium hydride (which had been washed free of mineral oil with petroleum ether) in 100 ml. of dimethylacetamide.
  • the resulting mixture is stirred at room temperature for minutes and 22 g. of abromo-pJrifluoromethylphenoxy acetic acid in 50 ml. of dimethylacetamide is added gradually.
  • the mixture is stirred at room temperature for 72 hours, then at 50C.
  • R represents n represents a whole number of from 1 to 4, inclusive
  • each R independently, represents hydrogen or lower alkyl
  • R represents hydrogen, halo or loweralkyl
  • R represents lower alkyl, propargyl, phenyl,
  • R,, R R and R each independently represents hydrogen, chloro, iodo or bromo, and R and R additionally each, independently, represents trifluoromethyl or phenyl, provided I. at least one of R and R is other than hydrogen, 2.
  • R R R and R each, independently, may not represent only chloro or hydrogen, 3.
  • R and R each, independently, represents trifluoromethyl or phenyl only a. when at least one of R R a R and R represents chloro, bromo or iodo, or b. when one of R and R represents a trifluoromethyl or phenyl group and the other of R and R represents the second group; or a non-toxic acid addition or quaternary salt thereof.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US768881A 1968-10-18 1968-10-18 Derivatives of acetic acid Expired - Lifetime US3681365A (en)

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US (1) US3681365A (enExample)
BE (1) BE740392A (enExample)
BR (1) BR6913405D0 (enExample)
CH (1) CH523862A (enExample)
DE (1) DE1951665A1 (enExample)
ES (2) ES372576A1 (enExample)
FR (1) FR2020998B1 (enExample)
GB (1) GB1267168A (enExample)
IL (1) IL33206A0 (enExample)
NL (1) NL6915206A (enExample)
ZA (1) ZA697336B (enExample)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4051170A (en) * 1973-12-15 1977-09-27 Merck Patent Gesellschaft Mit Beschrankter Haftung Diphenoxyacetic acid derivatives
EP0107640A1 (en) * 1982-09-30 1984-05-02 Monsanto Company Dialkyl glyoxylate surfactants

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102947939B (zh) 2010-06-21 2015-11-25 Abb技术有限公司 具有局部发射极短路点的改进模式的相位控制晶闸管

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3462446A (en) * 1966-11-25 1969-08-19 Parke Davis & Co Substituted beta-amino-2-stilbazole compounds
US3470234A (en) * 1965-08-23 1969-09-30 Ciba Geigy Corp Diaryl substituted benzocycloalkanes
US3476767A (en) * 1965-10-11 1969-11-04 Ciba Geigy Corp 1,2-diaryl - 6 - tertiary amino lower-alkoxy-3,4-dihydro naphthalenes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3470234A (en) * 1965-08-23 1969-09-30 Ciba Geigy Corp Diaryl substituted benzocycloalkanes
US3476767A (en) * 1965-10-11 1969-11-04 Ciba Geigy Corp 1,2-diaryl - 6 - tertiary amino lower-alkoxy-3,4-dihydro naphthalenes
US3462446A (en) * 1966-11-25 1969-08-19 Parke Davis & Co Substituted beta-amino-2-stilbazole compounds

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4051170A (en) * 1973-12-15 1977-09-27 Merck Patent Gesellschaft Mit Beschrankter Haftung Diphenoxyacetic acid derivatives
EP0107640A1 (en) * 1982-09-30 1984-05-02 Monsanto Company Dialkyl glyoxylate surfactants

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BE740392A (enExample) 1970-04-16
DE1951665A1 (de) 1970-04-30
CH523862A (de) 1972-06-15
FR2020998A1 (enExample) 1970-07-17
IL33206A0 (en) 1969-12-31
ES372576A1 (es) 1972-02-16
FR2020998B1 (enExample) 1974-08-30
BR6913405D0 (pt) 1973-01-04
NL6915206A (enExample) 1970-04-21
ES374593A1 (es) 1972-04-01
ZA697336B (en) 1971-07-28
GB1267168A (enExample) 1972-03-15

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