WO1999043656A1 - Derives de propylamine et utilisation - Google Patents

Derives de propylamine et utilisation Download PDF

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Publication number
WO1999043656A1
WO1999043656A1 PCT/JP1999/000759 JP9900759W WO9943656A1 WO 1999043656 A1 WO1999043656 A1 WO 1999043656A1 JP 9900759 W JP9900759 W JP 9900759W WO 9943656 A1 WO9943656 A1 WO 9943656A1
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WIPO (PCT)
Prior art keywords
compound
group
lower alkyl
butyl
phenylisoxazolyl
Prior art date
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PCT/JP1999/000759
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English (en)
Japanese (ja)
Inventor
Takeaki Matsui
Yuichiro Tanaka
Masaki Inoue
Shugo Etoh
Masatoshi Noda
Tetsuaki Yabuki
Tetsuo Toga
Hiroaki Amagishi
Maki Hayakawa
Chikage Tanaka
Yumi Matsumura
Original Assignee
Maruho Kabushikikaisha
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Publication of WO1999043656A1 publication Critical patent/WO1999043656A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/092—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings with aromatic radicals attached to the chain

Definitions

  • the compounds represented by are each known. However, these compounds are known as compounds having an anti-reserpine action or an antihypertensive action, and none of them are known to have a central muscle relaxing action. Disclosure of the invention
  • R 3 and R 4 are either a hydrogen atom or a lower alkyl group and the other is a lower cycloalkyl group, or the same or different and a lower alkyl group, or both of these lower alkyl groups;
  • the groups may be linked to each other with or without a nitrogen or oxygen atom to form a ring, wherein said ring may be substituted with lower alkyl, lower alkanol or aralkyl;
  • R 5 is a hydrogen atom, a lower alkyl group or an aryl group
  • the object compound of the present invention is a propylamine derivative having a carbamoyloxy group at the 1-position, that is, a novel compound represented by the above general formula [I] and a physiologically acceptable salt thereof. Further, the optical isomer of the compound [I] having an asymmetric center at the 1-position and the 2-position is also included in the target compound of the present invention.
  • the carbon atom adjacent to the substituent A of the propylamine derivative is conveniently named as 1-position.
  • the object compound of the present invention has an excellent central muscle relaxing action and an urinary reflex suppressing action.
  • heteroaryl group examples include a 5-membered ring group having one hetero atom such as a carboxy group, a furyl group and a pyrrolyl group, an imidazolyl group, a pyrazolyl group, a thiazolyl group, and an isothiazolyl group.
  • the number of substituents on the heteroaryl group is preferably 1 to 3 in the case of a 5- or 6-membered ring having 1 or 2 heteroatoms.
  • the above-mentioned hetero atom means a nitrogen atom, a sulfur atom and an oxygen atom as understood from the specific examples.
  • Oyobi 1 2 as a "Ariru group", phenyl group, a naphthyl group or ⁇ And anthranyl group.
  • aryl groups include halogen atoms (fluorine, chlorine, bromine, and iodine), hydroxy groups, nitro groups, cyano groups, amino groups, and lower alkyl groups (methyl, ethyl, n-propyl, isopropyl, n-butyl, and isobutyl).
  • ⁇ aralkyl group '' in 1 to 12 means a group in which the above aryl group and a lower alkyl group are bonded, and specific examples include benzyl, phenethyl, phenylpropyl, and naphthylmethyl. Among them, benzyl is preferred.
  • lower alkoxy”, “lower alkylthio” and “lower alkyl” in the “lower alkyl group substituted with lower alkoxy or lower alkylthio” for R 1 and R 2 are the same as those described above, and the lower alkyl group The number of the above substituents is preferably one.
  • Examples of the “lower alkyl group substituted by lower alkoxy or lower alkylthio” specifically include methoxymethyl, ethoxymethyl, methylthiomethyl, and ethylthiomethyl.
  • lower alkyl group for R 3 and R 4 in the general formula [I], those similar to the above can be mentioned.
  • lower cycloalkyl group include cyclopentyl, cyclohexyl and cycloheptyl.
  • the “ring formed by the lower alkyl group bonded to each other via a nitrogen atom or an oxygen atom or not” as R 3 and R 4 includes pyrrolidine, piberidine, hexamethyleneimine, morpholine, Pyrazine and the like, and among them, pyrrolidine and bipyridine are preferable. These rings may be substituted with a lower alkyl group, a lower alkanol group or an aralkyl group.
  • the “lower alkyl group” and “aralkyl group” include the same as those described above.
  • the term "lower alkanoyl group” means an alkanoyl group having 1 to 5 carbon atoms. Specific examples include formyl, acetyl, propionyl, petyryl, valeryl and the like.
  • lower alkyl group for R 5 in the general formula [I]
  • those similar to the above can be mentioned. Of these, methyl and ethyl are preferred as the lower alkyl group.
  • aryl group the same as the “aryl group” in R 1 and R 2 can be mentioned, and among them, phenyl and the like are preferable.
  • a physiologically acceptable salt of the compound [I] is also included in the target compound.
  • such salts include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, and formic acid, acetic acid, oxalic acid, cunic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, and methanesulfone. And salts with organic acids such as acid and lactic acid.
  • the compound [I] of the present invention has at least one asymmetric carbon atom and thus has two or more optical isomers, and those isomers and mixtures thereof are also included in the target compound of the present invention. Is done.
  • each diastereomer is also included in the target compound of the present invention.
  • Compound [I] can be synthesized, for example, by the following production method A to production method C.
  • the reaction reagent and the synthetic intermediate may be a commercially available compound, a compound described in the literature (for example, JP-A-7-10851, International Patents WO 95/18092 and WO 96/10567) or described in the literature. Or a compound produced according to the method.
  • the optically active compound may be prepared by asymmetric synthesis of the compound [V] in the production method C according to the production method (a), using the compound produced, or described in the literature (for example, see JP-A-7-1085). No. 1) or the production method described in the literature or a compound produced according to the method.
  • This production method is carried out by reacting the corresponding propyl alcohol (JP-A-7-10851, WO 96/10567, etc.) with phenyl chlorocarbonate and then with amine.
  • reaction with propyl alcohol [II] is carried out in an organic solvent in the presence of a base using chlorophenyl carbonate slightly in excess of a chemical equivalent at room temperature for about 30 minutes to 2 hours.
  • organic solvent at this time include pyridine, methylene chloride, tetrahydrofuran, and toluene.
  • base pyridine, triethylamine and the like can be used.
  • the above reaction product and the amine [III] are mixed at room temperature for about 30 minutes in an organic solvent. Allow to react for minutes to 12 hours.
  • the organic solvent at this time include alcohols such as methanol, ethanol, and 2-propanol.
  • the amine [III] include ammonia, methylamine, ethylamine, benzylamine and the like.
  • This process is carried out by reacting the corresponding propyl alcohol with isocyanate [IV] in an organic solvent.
  • This reaction is carried out at room temperature for about 30 minutes to 15 hours using a stoichiometric equivalent or a slight excess of isocyanate [IV] with respect to propyl alcohol [II] in an organic solvent.
  • isocyanates include ethyl isocyanate and phenyl isocyanate.
  • an acid catalyst such as trifluoroacetic acid may be added as needed.
  • the organic solvent at this time include methylene chloride and benzene.
  • This method is particularly preferable when R 5 is an aryl group in the target compound [I] of the present invention.
  • compound [I] is obtained by reacting compound [V] with amine [VI] in an organic solvent.
  • This reaction is carried out by reacting the compound [V] with a chemical equivalent or excess of the amine [VI] at about 0 140 ° C for about 1 hour to 4 days.
  • the organic solvent include alcohols such as methanol and ethanol, halogenated hydrocarbons such as chloroform and methyl chloride, and ethers such as ether and tetrahydrofuran.
  • aromatic hydrocarbons such as benzene, tol R Nene and the like, and amine [VI] may be used as the organic solvent.
  • Compound [V] can be produced by the following two methods.
  • the compound [VII] is reacted with a Lewis acid and an amine in an organic solvent, and the aldehyde [VIII] is subjected to an alditol condensation with the reaction product to obtain a compound [IX].
  • compound [VII] is first reacted with a chemical equivalent or an excess of Lewis acid, followed by a chemical equivalent or an excess of amine at about 180 to 0 ° C for about 10 minutes to 2 hours. It is performed by Subsequently, the compound [IX] is obtained by reacting the aldehyde [VIII], which is slightly in excess of the chemical equivalent, at about 180 ° C. to room temperature for about 10 minutes to 12 hours.
  • Examples of the Lewis acid include dibutyl boron triflate, titanium tetrachloride and the like.
  • Examples of the amine include triethylamine, N, N-diisopropylethylamine, N, N, N ,, N'-tetramethylethylenediamine and the like.
  • Examples of the organic solvent include methylene chloride, ether, toluene, and tetrahydrofuran, and among them, methylene chloride is preferable.
  • the compound [IX] can be asymmetrically synthesized by appropriately selecting reaction conditions such as the type and amount of Lewis acid, the type and amount of amine, the type of organic solvent, and the reaction temperature. .
  • the compound [IX] synthesized in a stereoselective manner is used to carry out the following steps (ii) to (V) and the above-mentioned production method C, whereby the compound [I] finally synthesized in a stereoselective manner is obtained. ] Can be obtained. ⁇ Process (ii)
  • Compound [X] is obtained by reacting compound [IX] obtained in step (i) with a base in a solvent.
  • This reaction is carried out by reacting compound [IX] with a chemical equivalent of a base at about 120 to 40 ° C for about 10 minutes to 12 hours.
  • a base water or Examples include alcohols such as methanol and ethanol.
  • the base include lithium hydroxide, sodium hydroxide, sodium methylate, sodium ethylate and the like, and alcoholate as a solvent is preferable. Among them, sodium methylate is more desirable.
  • compound [XI] is obtained by treating compound [X] obtained in step (ii) in the same manner as in production method A or production method B.
  • Compound [XII] is obtained by reacting compound [XI] obtained in step (iii) with a reducing agent in an organic solvent.
  • This reaction is carried out by reacting compound [XI] with a chemical equivalent or an excess amount of a reducing agent in an organic solvent at about 120 ° C. to reflux for about 1 to 24 hours.
  • a reducing agent include lithium borohydride, sodium borohydride-lithium chloride, and the like.
  • organic solvent ethers such as dry ether and dry tetrahydrofuran are used.
  • compound [V] is obtained by reacting compound [XII] obtained in the above step (iv) with P-toluenesulfonyl chloride or methanesulfonyl chloride in an organic solvent in the presence of a base.
  • the compound [XII] is reacted with p-toluenesulfonyl chloride or methanesulfonyl chloride in a stoichiometric amount to 4 times the amount at about -20 to 40 ° C for about 30 minutes to 2 days.
  • the organic solvent include pyridine, methylene chloride, tetrahydrofuran and the like
  • examples of the base include pyridine, triethylamine, N, ⁇ , ⁇ ′, ⁇ ′-tetramethylethylenediamine, potassium carbonate and the like.
  • A-CH— C CH 2 A-CH— CH—— CH 2 OH (Si)
  • the compound [XIV] is obtained by reacting the aldehyde [VIII] with the corresponding Grignard reagent [XIII] in an organic solvent.
  • This reaction is carried out by using a Grignard reagent [XIII], which is slightly in excess of the stoichiometric equivalent with respect to the aldehyde [VIII], and stirring at room temperature for about 5 minutes to 1 hour.
  • Aldehyde [VIII] may be synthesized by a method known in the literature, or can be synthesized from the corresponding carboxylic acid, ester or alcohol obtained by a method known in the literature by a conventional method.
  • Ethers such as dry ether and dry tetrahydrofuran can be used as the organic solvent.
  • Compound [XV] is obtained by treating compound [XIV] obtained in step (i) in the same manner as in Production method A or Production method B described above. 'Process (iii)
  • the compound [XV] obtained in the step (ii) is hydroborated, then oxidized and hydrolyzed in an organic solvent to obtain a compound [XII].
  • Hydroboration is carried out by reacting compound [XV] with a stoichiometric or excess borane compound in an organic solvent at room temperature for about 10 to 20 hours. Oxidation and hydrolysis of the obtained reaction product are carried out by reacting sodium hydroxide and hydrogen peroxide solution.
  • the borane compound include diborane, 9-borabicyclo [3.3.1] nonane, and the like. Ethers such as dry ether and dry tetrahydrofuran are used as the organic solvent. 'Process (iv)
  • Compound [V] is obtained by treating compound [XII] obtained in step (ii) in the same manner as in step (V) of production method (a) of compound [V] in production method C.
  • the compound [I] and a salt thereof of the present invention have a central muscular relaxation action, and are used as a therapeutic agent for diseases having spastic paralysis as a main symptom. Useful.
  • Rat superior and inferior dissection decerebrate rigidity (a rigidity) Remission is a method used to evaluate the main efficacy of muscle relaxants (Fukuda H., Yakugaku Zasshi, 1991, 111, 147 or Ono et al., Gen. Pharmacol., 1987, 18, 57), tolperisone hydrochloride (Fukuda et al., Chem. Pharm. Bull., 1974, 22, 2883) and eperisone hydrochloride (Tanaka et al "Nippon Yakurigaku Zasshi, 1981). It has been shown that existing central muscle relaxants such as, 77,511) also have a remission effect on the cerebellar decerebrate rigidity (a rigidity) between the superior and inferior colliculi.
  • the compound [I] of the present invention and a salt thereof are useful as central muscle relaxants, and include, for example, painful spasms associated with musculoskeletal disorders; scapulohumeral syndrome, shoulder peri-arthritis, lumbago or Improvement of muscle tone due to spondyloarthropathy; cerebrovascular disorder, spinal cord palsy, cervical spondylosis, cerebral (child) palsy, post-operative sequelae (including brain and spinal cord tumors), sequelae of trauma (spinal cord injury, Head trauma), spinocerebellar degeneration, multiple sclerosis Syndrome, amyotrophic lateral sclerosis, spinal vascular disorders, SMON, ossification of the posterior longitudinal ligament, sequelae of stroke, other cerebral spinal cord diseases or other paralysis due to myelobees; rigidity in Parkinson's syndrome It can be used as a muscle relaxant for improving the condition.
  • the compound [I] of the present invention and a salt thereof are also useful as a therapeutic agent for pollakiuria and urinary incontinence, for example, neuropathic bladder, unstable bladder, bladder irritation
  • Formulations for oral administration include, for example, tablets, pills, powders, granules, fine granules, capsules, solutions, suspensions, emulsions, etc.
  • Formulations for parenteral administration include injections , Drops, suppositories, ointments, plasters, patches, aerosols and the like. These formulations can be manufactured by conventional methods commonly known in the art.
  • tablets can be prepared using conventional excipients such as lactose, starch, microcrystalline cellulose, binders such as starch solution, carboxymethyl cellulose, disintegrants such as dried starch, calcium carbonate, sucrose, stearic acid, cocoa butter, Disintegration inhibitors such as hydrogenated oil, quaternary ammonium base, absorption promoters such as sodium lauryl sulfate, Using humectants such as Lyserine and starch, adsorbents such as starch, lactose, kaolin, bentonite and colloidal keic acid, lubricants such as purified talc, stearates, boric acid powder, polyethylene glycol, etc. It is manufactured by a conventional method.
  • excipients such as lactose, starch, microcrystalline cellulose, binders such as starch solution, carboxymethyl cellulose, disintegrants such as dried starch, calcium carbonate, sucrose, stearic acid, cocoa butter,
  • excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin, and silk
  • binders such as gum arabic, tragacanth, gelatin, and disintegrants such as laminaran and agar. And is manufactured by an ordinary method.
  • Suppositories can be prepared according to a conventional method after adding a base and, if necessary, a surfactant to the active ingredient of the present invention.
  • Suppository bases include, for example, macrogol, lanolin, cocoa oil, fatty acid triglycerides, witepsol (dai An oily base such as (Namaite Novels) can be used.
  • the ointment is formulated by mixing a base ordinarily used for the active ingredient of the present invention and, if necessary, a carrier such as a stabilizing agent, a wetting agent and a preservative, and mixing them by a conventional method.
  • Ointment bases include liquid paraffin, white petrolatum, beeswax, octyldodecyl alcohol, paraffin and the like.
  • the preservative include methyl paraoxybenzoate, ethyl parahydroxybenzoate, propyl paraoxybenzoate, and the like.
  • Example 6 (6) and 0.52 g (1.2 mmol) of (1 S, 2R) -15- (1-force rubamoyloxy-12-tosyloxymethyl) butyl-3-phenylisoxazol In the same manner, 0.35 g of (IS, 2R) —5 -— [1-hydroxyl-bamoyloxy 2 -— (1-pyrrolidinylmethyl) butyl) -13-phenylisoxazozol (light yellow crystals, 90%).
  • Example 10 The same treatment as in Example 10 (1) was carried out except that ethylamine was used instead of ammonia in (1), to give 5- (3-dimethylamino-1-hydroxy-2,2-dimethylpropyl) 13.
  • ethylamine was used instead of ammonia in (1), to give 5- (3-dimethylamino-1-hydroxy-2,2-dimethylpropyl) 13.
  • Phenylisoxazolyl 4.12 g (10.0 mmol) from 5— [3-Dimethylamino-11- (N-ethylcarbamoyloxy) -1,2,2-dimethylmethylpropyl] —3-Phenylisozo 3.24 g of colorless crystals of oxazole were obtained.
  • Diastereomer B (1-hydroxy-12-methyl-3- (3-methylbiperidino) -1-1 (4-trifluoromethylphenyl)) obtained in (1) above 3.57 g (1 1 (3 mmol) was converted to rubamoyl in the same manner as in Example 10 (1) to give colorless crystals of 1-rubumyloxy-2-methyl-3- (3-methylbiperidino) -1- (4-trifluoromethylphenyl). ) 4.08 g of propane were obtained.
  • Diastereomer A (1- (4-ethylphenyl) -11-hydroxy-12-methyl-3- (1-1-pyrrolidinyl) propane hydrochloride obtained in (1) above) (Melting point 163-166 ° 0 treated with base Example 21 (1) was obtained by adding 5.21 g (21.1 mmol) of the free product obtained by the reaction, 11- (4-ethylphenyl) -11-hydroxy-12-methyl-13- (1-pyrrolidinyl) propane, to Example 10 (1). Then, 3.06 g of colorless crystals of 1-force rubamoyloxy-11- (4-ethylphenyl) -12-methyl-13- (1-pyrrolidinyl) propane were obtained.
  • test compound was dissolved in distilled water for injection and orally administered under the conditions of a dose of 100 mg / 5.0 ml / kg (equivalent to the free form).
  • the decerebrate rigidity-releasing action of Compound C was evaluated in comparison with Compounds b and c in the same manner as in Test Examples 11-11. However, the dose was 50. Omg / 5.0 ml / kg (converted to free substance) and orally administered. Table 2 shows the results.
  • Test compounds were administered intravenously or orally, blood was collected from the jugular vein over time, and plasma concentrations were measured by LC-MS / MS. The test compound was dissolved in physiological saline or 0.5% aqueous methylcellulose solution. The area under the plasma concentration-time curve (AUC) was calculated from the obtained plasma concentration to determine the bioavailability. Table 3 shows the results.
  • the male SD rats were anesthetized with urethane 50 O mg / kg, i.p. and sodium chloralose 5 O mg / kg, i.p., and fixed in a dorsal position. After securing a spontaneous respiration by inserting a tracheal force neura, a midline incision is made in the lower abdomen to expose the bladder, and a polyethylene tube is inserted through a small incision added to the top of the bladder. The change in pressure was measured. After ligating the urethra, rhythmic bladder contraction was induced by injecting saline into the bladder and increasing the intravesical pressure.
  • test compound was dissolved in distilled water for injection, and administered via a force transducer inserted into the duodenum or external vein. After administration of the test compound, the time required for bladder rhythmic contraction to disappear and rhythmic contraction to develop again was measured, and the urinary reflex inhibitory effect was evaluated using this time as an index.
  • Table 4-1 shows the results of intravenous administration
  • Table 4-2 shows the results of intraduodenal administration.
  • Compound D exhibits an inhibitory effect on micturition reflex by intravenous administration that is equal to or higher than that of Compound d as a control drug, and that by duodenal administration is higher than that of Compound d.
  • Test Example 5 Acute toxicity
  • test compound A was administered once to rats, and the acute toxicity was examined.
  • Test compound Lethal dose * (mg / kg)
  • the target compound of the present invention is useful as a central muscle relaxant and a therapeutic agent for dysuria.

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

Abstract

L'invention concerne des dérivés de propylamine représentés par la formule ci-après et des sels de ces dérivés. Dans ladite formule, A est aryle substitué par halogéno, etc., ou hétéroaryle éventuellement substitué; R1 et R2 sont des alkyles inférieurs identiques ou différents, ou bien l'un des deux éléments R1 et R2 est hydrogène, l'autre étant alkyle inférieur, alcoxy inférieur, aryle, etc.; l'un des deux éléments R3 et R4 est hydrogène ou alkyle inférieur et l'autre est cycloalkyle inférieur, ou bien R3 et R4 sont des alkyles inférieurs identiques ou différents ou sont liés pour former ensemble une chaîne qui comporte un ou plusieurs atomes d'azote ou d'oxygène, avec substitution éventuelle par alkyle inférieur, etc.; et R5 est hydrogène, alkyle inférieur, ou aryle.
PCT/JP1999/000759 1998-02-25 1999-02-19 Derives de propylamine et utilisation WO1999043656A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP4399898 1998-02-25
JP10/43998 1998-02-25

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WO1999043656A1 true WO1999043656A1 (fr) 1999-09-02

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2285787A4 (fr) * 2008-06-05 2012-04-25 Sk Biopharmaceuticals Co Ltd Composés de propanamine à substitution 3
US8404730B2 (en) 2008-06-05 2013-03-26 Sk Biopharmaceuticals Co., Ltd. 3-substituted propanamine compounds
EP3946460A4 (fr) * 2019-04-05 2023-03-29 Prolynx LLC Lieurs de conjugaison améliorés

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5716841A (en) * 1980-05-22 1982-01-28 Bayer Ag Novel compound,manufacture,bactericidal composition and use

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5716841A (en) * 1980-05-22 1982-01-28 Bayer Ag Novel compound,manufacture,bactericidal composition and use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
AVRAMOVA P., DRYANOVSKA L., ILARIONOV Y.: "SYNTHESIS AND PHARMACOLOGIC ASSESSMENT OF CARBAMIC AND CARBONIC ACID ESTERS WITH 1-ARYL-3-DIMETHYLAMINO-1-PROPANOLS.", PHARMAZIE, vol. 38., no. 07., 1 January 1983 (1983-01-01), pages 443/444., XP002920580, ISSN: 0031-7144 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2285787A4 (fr) * 2008-06-05 2012-04-25 Sk Biopharmaceuticals Co Ltd Composés de propanamine à substitution 3
JP2012528788A (ja) * 2008-06-05 2012-11-15 エスケー バイオファーマスティカルズ カンパニー リミテッド ３−置換プロパンアミン化合物
US8404730B2 (en) 2008-06-05 2013-03-26 Sk Biopharmaceuticals Co., Ltd. 3-substituted propanamine compounds
KR101603487B1 (ko) * 2008-06-05 2016-03-17 에스케이바이오팜 주식회사 3-치환된 프로판아민 화합물
EP3946460A4 (fr) * 2019-04-05 2023-03-29 Prolynx LLC Lieurs de conjugaison améliorés

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