Classifications

• • 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
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
  • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
  • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/12—Antihypertensives
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/004—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with organometalhalides
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
  • C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups

Definitions

• esters of the levorotatory enantiomorph of erythro 3-hydroxy-a-(1-aminoethyl)-benzyl alcohol relate to esters of the optically active threo 3-hydroxy-a-( l -aminoet'hyl)-benzyl alcohol.
• the absolute configuration of optically active compounds can be described by using the sequence rule procedure.
• the four groups attached to an asymmetric carbon atom, C are assigned priorities and arranged in sequence so that the sterochemical symbols R or S may be determined.
• the asymmetric carbon atom is viewed from the side opposite to the group of lowest priority, d, then proceeding from a to b to c traces either a clockwise or a counterclockwise course. If the course is clockwise, then the symbol R is used to describe the stereochemistry at this asymmetric carbon atom. If it is counter-clockwise, the symbol S is used.
• the procedure is applied to each and the stereochemistry is expressed as a mu]- tiplicity of R or S symbols.
• the hydroxyl-bearing carbon of the side chain is designated 1 and the nitrogen-bearing carbon is designated 2.
• Metaraminol or erythro 3-hydroxy-a-( laminoethyl)-benzyl alcohol (1R,2S configuration), has recently been reported to be an antihypertensive agent in man [J. R. Crout, R. R. Johnston, W. R. Webb, and P. A. Shore, Clin. Res., 13, 204 (1965) and J. R. Crout, Circulation Res., 18, 19 Suppl. 1, 1-120 (1966)]. This antihypertensive action is believed to result from the release and replacement of norepinephrine in adrenergic nerves by metaraminol.
• ester derivatives of 3-hydroxy-a- (l-aminoethyl)-benzyl alcohol can also release norepinephrine from mouse heart tissue. We have also found that these derivatives are cleaved, in vivo, to yield metaraminol.
• novel ester derivatives of erythro 3-hydroxy-a-(1-aminoethyl)- benzyl alcohol (1R,2S), including the 3-ether derivatives thereof such as the benzyl ethers and the halogen substituted benzyl ethers are especially superior to metaraminol in that they do not cause the initial increases in blood pressure and heart rate which are sometimes found with metaraminol.
• novel ester derivatives of 3-hydroxy-a-.( l-aminoethyl)-benzyl alcohol can be used as inhibitors of gastric secretion.
• the compounds of this invention may be associated with a carrier which may be either a solid material or a sterile parenteral liquid.
• the composition may take the form of tablets, powders, capsules or other dosage forms particularly useful for oral ingestion. Liquid diluents are employed in sterile condition for parenteral use.
• the compounds of this invention are given to patients in doses of 5 to 500 mg. per day. Preferably they are used orally in the range of 5 to 500 mg. per day in divided doses.
• R is hydrogen
• R5 512 or RA-ttl wherein R is hydrogen, alkyl, substituted alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkoxy, phenyl, substituted phenyl, benzyl, substituted benzyl or a heterocyclic radical; R is hydrogen, alkyl, phenyl or substituted phenyl; R is hydrogen, alkyl, or phenyl; X is hydrogen, halogen, hydroxy, alkoxy, alkyl, phenyl or and wherein R and R can be combined to form a saturated or unsaturated alicyclic or-heterocyclic ring; n is 0 or l; R is hydrogen or lower alkyl; each R is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, a heterocyclic radical, cycloalkyl, alkenyl or cyclo
• the compounds of this invention are esters of a 3-hydroxy-a-(1- aminoethyl)-benzyl alcohol, the acyl group of the ester being bonded to the hydroxy group of the alkyl side chain of the parent compound.
• the invention further contemplates the 3-ester and 3-ether derivatives of such esters, as well as ring-substituted analogs of the 3- hydroxy, 3-ether and 3-ester compounds. These compounds may have the erythro or threo configuration, and may be the racemic mixture or substantially pure enantiomorphs.
• each of R R, R R and X may be alkyl.
• alkyl groups When alkyl groups are present in the compound, they will preferably be lower alkyl, that is alkyls of less than about seven carbon atoms. Examples of such groups are the methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, amyl and hexyl groups.
• the substituents present can include halogens, typified by chloro, bromo or fluoro; aryl groups, typified by phenyl, tolyl, chlorophenyl, anisyl,
• Each of R and R can be cycloalkyl of up to seven carbon atoms in the ring, including cyclopentyl and cyclohexyl; or cycloalkenyl of up to seven carbon atoms in the ring, including cyclopentenyl, cyclohexenyl or cyclohexadienyl.
• R, R, R, R and X can be phenyl.
• the substituents can be halogen, preferably chloro or fluoro; lower alkyl; perfluoro lower alkyl such as trifluoromethyl, lower alkoxy such as methoxy, ethoxy, propoxy or isopropoxy, hydroxy, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, nitro, sulfamoyl, alkylsulfonamido or phenyl.
• the heterocyclic radical can be any three to seven membered saturated or unsaturated ring containing one or more hetero atoms such as sulfur, oxygen or nitrogen atoms.
• the heterocyclic radicals can be those carrying substituents such as lower alkyl, halogen (chloro, bromo, iodo or fluoro) or methoxy.
• Representative heterocycles from which the radicals R and R can be derived are: pyridine, furan, pyran, thiophene, 4- methylpyridine, pyrazine, pyridine-N-oxide, pyrimidine, thiazole, imidazole and benzimidazole.
• Each of R and X may be alkoxy, suitably a lower alkoxy group, where the lower alkyl portion of the group is as defined above.
• Each of R and R can be benzyl or substituted benzyl, the possible substituents being the same as those noted above for the phenyl group.
• Each of R and R may be alkenyl, suitably lower alkenyl, illustrated by ally], vinyl and l-(4-pentenyl).
• R is hydrogen or lower alkyl, e.g., methyl or ethyl.
• the ring formed is preferably a 3-7-membered ring such as cyclopentyl, cyclohexyl, cyclohexenyl, phenylcyclohexyl, piperazinyl, pyridyl or pyridyl-N-oxide.
• the saturated or unsaturated alicyclic or heterocyclic radicals can also be substituted with phenyl substituents.
• n will be when the ether carbon atom C is joined to either R or R through an unsaturated bond. In'al'l other cases n will be 1.
• the preferred compounds are those of erythro configuration, and especially the isomers having the 1R,2S side chain configuration.
• the compounds found most useful for reducing blood pressure are those wherein R is hydrogen, phenyl, substituted phenyl, or lower alkyl; R, R, R and X are hydrogen; and R is hydrogen, lower alkyl, phenyl or substituted phenyl, especially pchlorophenyl, m-chlorophenyl or m-fluorophenyl and those wherein R is hydrogen, phenyl, substituted phenyl or lower alkyl and R, R and X are hydrogen. Where the compound contains a plurality of R groups, they need not all be the same.
• novel compounds of this invention are the formate, acetate, propionate, butyrate, benzoate, trichloroacetate, cyclohexanoate, acrylate, methacrylate, p-chlorobenzoate, p-methoxybenzoate, p-dimethylaminobenzoate, picolinate and phenylacetate esters of the racemic and optically active forms having the IR, 28 configuration of Erythro 3-(hydroxy, formyloxy, acetoxy, propionyloxy, butyryloxy, trichloroacetoxy, benzoyloxy)-a-( l-aminoethyl)-benzyl alcohol;
• racemic threo compounds are also intended to be included in this invention as well as the optically active forms of the erythro and threo configuration.
• the compounds of this invention are readily prepared by a number of methods, the most convenient of which involve the reaction of an N-blocked a-(laminoethyl)-b'enzyl alcohol with a reactive derivative of an acid R,COOl-I, such as the acid halide or anhydride, followed by removal of the N-blocking group.
• the compounds can be prepared by rearrangement of a suitable N-acyl derivative. The precise benzyl alcohol derivative selected as the reactant will be determined by the desired end product.
• novel compounds can be prepared by rearrangement of an N-acylated-a-(l-aminoethyl)-benzyl alcohol or an N-acylated-3-(2-amino-l-chloropropyl)- phenol under acidic conditions according to the reaction:
• HY is the acid employed and Z is hydroxyl (OH) or halogen, preferably chlorine.
• Z is hydroxyl, the reaction can be represented as:
• the above reaction is preferably carried out in an inert diluent such as a lower alkanol.
• Reaction temperatures of the order of from about C. to the boiling point of the solvent are suitable, with temperatures in the upper part of the range being preferred. Atmospheric pressure is generally satisfactory, although higher and lower pressures can also be used.
• the acid employed should be a strong acid, preferably a mineral acid such as hydrochloric, sulfuric or phosphoric acid.
• the group R may be any of those hereinbefore described, particularly alkyl, phenyl or substituted phenyl.
• the products are isolated and purified by conventional techniques, including solvent extraction, recrystallization etc.
• R' is hydrogen
• R' is esterified with a reactive derivative of an acid, the acid moiety being either the same or different from thatattached to the alpha-car bon of the side chain, to produce compounds of the in- 6 vention wherein R is In any such subsequent esterification, the amino nitrogen should be protected by salt formation or by a suitable blocking group.
• the acid employed can be any strong acid, preferably a mineral acid such as sulfuric, hydrochloric or phosphoric acids or acidic salts thereof.
• the product will usually be obtained as the acid addition salt of the amine.
• the reaction is preferably carried out in an inert liquid diluent, such as a lower alkanol, containing a small quantity of water. Elevated temperatures in the range of about 30C. to the boiling point of the solvent are typically used, with the higher temperatures being preferred. Atmospheric pressure is suitable, although higher or lower pressures may be used.
• the reaction proceeds with inversion of the configuration of the alpha-carbon of the side-chain, and thus the threo reactant gives erythro product, and vice versa.
• Another method for preparing compounds of the invention is by reaction of an N-blocked a-( laminoethyl)-benzyl alcohol compound with an acid halide or anhydride of the acid RCOOH according to the equation:
• the N-blocking group R may be any group which is 5 stable during the acylation reaction but which can be ertly ring-substituted derivatives thereof, the t-butoxycarbonyl group, the triphenylmethyl (trityl) group, the benzyloxymethyl group, the pivaloyloxymethyl group and the like.
• the acid derivative employed as a reactant can be an acid halide, preferably an acid chloride or bromide, or an anhydride of the acid R COOH.
• the reaction is preferably carried out in a liquid diluent and in the presence of a base to take up the equimolar quantities of acid produced.
• Suitable bases are tertiary amines such as triethyl amine and pyridine, and these amines may serve also as the medium for the reaction.
• the reaction is preferably carried out at elevated temperatures ranging from about 30C. to the boiling point of the solvent, with the higher temperatures being preferred. Atmospheric pressure is suitable for the reaction, but higher or lower pressures may also be used.
• R is hydrogen
• an excess of the acid halide or anhydride can be employed in order to esterify both the side-chain and phenolic hydroxy groups.
• the desired product compound is one wherein R is hydrogen, it is most efficient to provide an O-blocking substituent on the phenolic hydroxyl group during the acylation reaction, to avoid side reactions and loss of starting material. Any group which is stable throughout the reaction but is subsequently removable, preferably by catalytic hydrogenation or selective hydrolysis, can be used.
• Illustrative suitable O-blocking groups are benzyl, inertly ring-substituted benzyl, methoxymethyl, triphenylmethyl and the like.
• N- blocking group and O-blocking group if any, is accomplished by a technique suitable for the particular groups involved.
• the preferred method is by catalytic hydrogenation using a noble metal catalyst such as palladium, or platinum oxide. Selective acid or base hydrolysis may also be used where applicable.
• the compounds VI can be prepared by the following sequence:
• compound VIII is acylated by reaction with a lower alkanoyl halide or anhydride to give compound XI.
• compound XI is converted to the phenolic ethers by reaction with the appropriate organic halide or the equivalent tosylate, mesylate, brosylate or quaternary ammonium compound to give compound X which is deacylated by acid or base hydrolysis to give compound IX. Further disclosure of methods for preparing compound IX is given in U.S. Pat. appli-' cation Ser. No. 636,586, filed May 8, I967.
• lustrative compounds R-Hal include trityl chloride
• the reaction is carried out under normal conditions for reactions of amines with organic halides, including the use of liquid diluent and a base to take up the mole of halogen acid formed.
• the preferred bases are tertiary amines such as triethyl amine and pyridine, which may also function as the diluent.
• the acid chloride can be replaced by other equivalent acid halides or anhydrides.
• the reaction conditions are generally similar to those described above for the preparation of compound IV.
• any general method for resolving amines particularly the method of forming an optically active salt using optically active acids such as optically active tartaric acid, dibenzoyl tartaric acid, camphor sulfonic acid, or mandelic acid, and separating the diastereoisomers followed by liberation of the optically active base can be used.
• optically active acids such as optically active tartaric acid, dibenzoyl tartaric acid, camphor sulfonic acid, or mandelic acid
• Other resolution methods such as spontaneous resolution or resolution by enzymatic means are equally applicable and can also be used to isolate the erythro or threo enantiomorphs from the racemic mixtures.
• the amine salts such as the mesylate, sulfate, hydrochloride, hydrogen maleate, fumarate and hydrogen tartrate salts are useful both therapeutically and in purifying the compounds by recrystallization.
• amine salts are readily prepared by treating the free amine with the desired acid in a suitable solvent such as a lower alkanol and thereafter precipitating the salt by adding a The reduction is run at anywhere from room temperature to the reflux temperature of the particular solvent used for a time sufficient to complete the reaction. The desired product can then be isolated from the reaction mixture by methods known in the art.
• a 10 percent aqueous sodium hydroxide solution is added dropwise to a cold, stirred mixture of 30.0 g. (0.0805 mole) of the hydrogen maleate salt of erythro a-(1-amino-ethyl)-m-benzyloxybenzyl alcohol, 300 ml. of water and 300 ml. of acetone until the pH of the solution remains at 8.5.
• a solution of benzoyl chloride, 1.9 g. (0.0135 mole) in 50 ml. of anhydrous pyridine is added slowly to a stirred solution of 5.0 g. (0.0128 mole) of the product from Step (a) in ml. of anhydrous pyridine at 100C. After the addition is complete, the reaction mixture is stirred at 100 C. for an additional hour and then allowed to cool to 20-30C. over 18 hours. Pyridine is removed under reduced pressure and the residual oil is dissolved in 200 ml. of ethyl acetate. The solution is washed with 200 ml. of water containing 1 ml.
• Diesters are obtained by using erythro a-( 1 aminoethyl)-3-hydroxybenzyl alcohol in Step (a) to give the corresponding N-carbobenzyloxy derivative and an excess (at least two molar equivalents) of the acid chloride in Step (b).
• erythro a-(laminoethyl)-3-benzoyloxybenzyl benzoate is obtained from erythro a-(1-[N-carbobenzyloxy]-aminoethyl)-3- hydroxybenzyl alcohol and an excess of benzoyl chloride by the procedure of Step (b).
• Erythro 3- acetoxy-a-(1-aminoethyl)-benzyl acetate is obtained by the same procedure using an excess of acetyl chloride in Step (b).
• the methylene chloride solution is washed with an aqueous sodium bicarbonate solution and dried over anhydrous sodium sulfate. After filtering the drying agent, methylene chloride is evaporated under reduced pressure and the residue is dissolved in ethyl ether. The ether solution is washed with a 5 percent sodium hydroxide solution and water and then dried over anhydrous sodium sulfate and filtered. Removal of the ether solvent and recrystallization of the residue from hexane gives 50.5 g. (78 percent) of the a-bromo ketone, m.p. 46.5-49.0C.
• Step (b): Preparation of m-benzyloxy-adibenzylaminopropiophenone hydrochloride A solution of33.5 g. (0.105 mole) of m-benzyloxy-abromopropiophenone and 43.4 g. (0.220 mole) of dibenzylamine in 400 ml. of absolute ethyl alcohol is stirred at reflux for 6 hours. The cooled reaction mixture is filtered and the filtrate concentrated under reduced pressure. The residue is extracted with ethyl ether which is then washed with water and dried over anhydrous sodium sulfate.
• the m-benzyloxy-a-dibenzylaminopropiophenone hydrochloride 4.26 g. (9.03 mmole)
• the ethyl ether extract is washed with water and dried over anhydrous magnesium sulfate.
• the filtered ethyl ether extract is added over one-half hour to a well-stirred mixture of 0.3 g. of lithium aluminum hydride and 20 ml. of dry ethyl ether under nitrogen. After stirring for 4 hours at reflux, the reaction mixture is cooled in an ice bath and excess lithium aluminum hydride is decomposed with a saturated sodium-potassium tartrate solution. The resulting viscous aqueous mixture is extracted several times with ethyl acetate. The combined ethyl acetate extracts are washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate and filtered. Solvent is evaporated under reduced pressure to give 3.2 g.
• This threo compound is reacted with acetic anhydride according to the process of Example 1, Step (at) to form the a-( l-acetamidoethyl) derivative, which hydroxybenzyl acetate.
• This a-(l-acetamidoethyl) compound is converted by the acid-catalyzed rearrangement of Example 1, Step (b) to give ()erythro-a-(l-aminoethyl)-3- methoxybenzyl acetate (1R,2S).
• the racemic erythro 3- methoxy acetyl ester is obtained.
• racemic erythro a-(1-aminoethyl)-3-methoxybenzylbenzoate is produced from racemic erythro a-(1-benzamidoethyl)- 3-hydroxybenzyl alcohol by following Example 6 and the acid catalyzed rearrangement of step (b), Example 2.
• the racemic erythro a-(1-benzamidoethyl)-3- hydroxybenzyl alcohol is prepared from the racemic erythro a-(1-aminoethy1)-3-hydroxybenzyl alcohol according to step (a), Example 2.
• a solution of 2.1 g. (0.018 mole) of freshly distilled isoamyl nitrite in 50 ml. of anhydrous ethyl ether is added dropwise to a solution of 3.0 g. (0.017 mole) of 3-methoxy-6-methyl-propiophenone in 50 ml. of anhydrous ethyl ether at room temperature. Dry hydrogen chloride gas is bubbled continuously through the reaction mixture during the addition and for an additional one-half hour after addition is complete. The reaction mixture is then stirred at room temperature for 3 hours.
• a mixture of 1.5 g. (0.0044 mole) of 3-methoxy-6- methyl-a-aminopropiophenone hydrochloride and 0.5 g. of a percent palladium on carbon catalyst in 30 ml. of water is hydrogenated at atmospheric pressure and 25C. until one equivalent of hydrogen has been absorbed.
• the reaction mixture is filtered and concentrated under vacuum to give a white solid, which after two recrystallizations from an ethanol-ethyl ether mixture affords 1.3 g. (87 percent) of the erythro a-(laminoethyl)-3-methoxy-6-methylbenzyl alcohol hydrochloride, m.p. 249250C. dec.
• a stirred mixture of 8.8 g. (0.043 mole) of erythro al-acetamidoethyl)-3-hydroxybenzyl alcohol prepared from racemic erythro a-(l-aminoethyl)-3- hydroxy-benzyl alcohol by the procedure in step (a), Example 1), 30.0 g. of anhydrous potassium carbonate, 10.0 g. (0.0487 mole) of m-chlorobenzyl bromide and 500 ml. of Merck reagent grade acetone is heated at reflux for hr.
• the warm reaction mixture is filtered and the filtrate concentrated under vacuum at water aspirator pressure (40-70C.) to an orange oil.
• the oil is dissolved in a mixture of 100 ml. ofwater and 100 ml. of ethyl acetate, treated with a 10 percent sodium hydroxide solution to pH 9 and the organic layer separated. After extracting the aqueous layer with 3 more 150 ml. portions of ethyl acetate, the ethyl acetate extracts are combined and washed with two -ml. portions of water.
• the organic extracts are dried over anhydrous sodium sulfate, filtered and con-, centrated under vacuum at water aspirator pressure (40-70C) to an orange oil.
• the residue is dissolved in a mixture of 50 ml. of a 10 percent sodium hydroxide solution and ml. of ethanol and stirred at reflux for 18 hr.
• the reaction mixture is concentrated under vacuum at water aspirator pressure (40-70C.) to remove most of the ethanol.
• One hundred ml. of water is added to the residue which is then saturated with sodium chloride and extracted with three 75-ml. portions of ethyl acetate.
• the ethyl acetate extracts are combined, dried over anhydrous sodium sulfate, filtered and concentrated under water aspirator vacuum at 40-70C. togive the m-chlorobenzyl ether as a yellow oil.
• the purified tartrate salt of the levorotatory aminoalcohol is suspended in water and shaken with a dilute sodium hydroxide solution and ethyl ether until solution is complete.
• the ether layer is washed with water, dried over sodium sulfate, filtered and concentrated.
• This optical isomer is converted to the desired erythro a-(1 aminoethyl)-3-(m-chlorobenzyloxy)- benzyl benzoate according to the process of Example 4, substituting benzoyl chloride for the 2-methylbenzoyl chloride of Step (b).
• racemic erythro product of Step (c) of this Example racemic erythro benzoate is obtained.
• Treatment of the racemic erythro product of Step (0) of this Example according to the process of Example 1 produces erythro a-(l-aminoethyl)-3-(m-chlorobenzyloxy)-benzyl acetate.
• erythro a-(l-ethylaminoethyl)-3-hydroxybenzyl benzoate is prepared according to the process of Example 4 from benzoyl chloride and erythro a-(l-ethylaminoethyl)-3- hydroxybenzyl alcohol which is, in turn, prepared by reducing the a-(l-acetamidoethyl) compound of Example l, Step (a) with lithium aluminum hydride in ethyl ether.
• R, R and X are hydrogen.
• a compound of claim 1 wherein X is hydrogen.
• ⁇ H CH3I 5 A compound of claim 1 in the erythro configura- NHRS tion.
• X 0 6.
• R g 9.
• a compound of claim 1 being erythro a-(laminoethyl)-3-(m-chlorobenzyloxy)-benzyl acetate.
• a compound of claim 1, being erythro a-(laminoethyl)-3-(m-chlorobenzyloxy)-benzyl benzoate.
• a compound of claim 1 being erythro a-(l' aminOethyD-S-methoxybenzyl acetate.
• E 13 A compound of claim 1, being erythro a-(l- 0 aminoethyl)-3-methoxybenzylbenzoate.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Public Health (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Engineering & Computer Science (AREA)
• Epidemiology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Emergency Medicine (AREA)
• General Chemical & Material Sciences (AREA)
• Heart & Thoracic Surgery (AREA)
• Cardiology (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=25294452

Family Applications (1)

Country Status (14)

Cited By (10)

Families Citing this family (2)

Citations (1)

Family Cites Families (1)

• 1969
  • 1969-07-10 US US00845120A patent/US3714229A/en not_active Expired - Lifetime
  • 1969-12-05 BR BR214798/69A patent/BR6914798D0/pt unknown
• 1970
  • 1970-06-18 ZA ZA704157A patent/ZA704157B/xx unknown
  • 1970-06-25 NL NL7009390A patent/NL7009390A/xx unknown
  • 1970-07-01 IL IL34831A patent/IL34831A0/xx unknown
  • 1970-07-02 AU AU17100/70A patent/AU1710070A/en not_active Expired
  • 1970-07-06 GB GB32589/70A patent/GB1273653A/en not_active Expired
  • 1970-07-08 CH CH1033670A patent/CH565138A5/xx not_active IP Right Cessation
  • 1970-07-09 BE BE753237D patent/BE753237A/fr unknown
  • 1970-07-09 SE SE7009536A patent/SE383511B/xx unknown
  • 1970-07-09 ES ES381597A patent/ES381597A1/es not_active Expired
  • 1970-07-09 DK DK358870AA patent/DK138418B/da unknown
  • 1970-07-10 FR FR707025768A patent/FR2059503B1/fr not_active Expired
  • 1970-07-10 JP JP45060028A patent/JPS5220463B1/ja active Pending

Patent Citations (1)

Also Published As

Similar Documents