Process for producing piperidine derivatives of esters of 4,5-dialkyl-3-oxy-pyrrol-2-carboxylic acid

专利摘要:

公开号:SU957768A3
申请号:SU802990879
申请日:1980-10-10
公开日:1982-09-07
发明作者:Фрикель Фритц-Фридер；Франке Альбрехт；Фон Филипсборн Герда；Д.Мюллер Клаус；Ленке Дитер
申请人:Басф Аг (Фирма)；
IPC主号:

专利说明:

. or - (CHj.) 1-3 C t. . is reacted with a piperidine derivative of the general formula -os, R where they have the indicated values in an organic solvent at 70-120 ° C, if necessary in the presence of an acid acceptor, and the resulting compound is liberated or in the form of a salt with physiological compatible acid. The reaction is expediently carried out at an equimolar ratio of the components in the presence of an organic solvent, for example, a lower C alcohol, such as methanol, ethanol or propanol, a lower saturated dialkyl ether, dialkyl glycol ether, such as diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran or dioxane, an aromatic hydrocarbon, such as benzene or alkyl benzene, such as toluene or xylene, or a saturated aliphatic hydrocarbon, such as hexane heptane or octane, lower aliphatic ketone about as acetone, methyl ethyl ketone or methyl isobutyl ketone, dialkilformamyda, such as dimethyl or diethylformamide or dimethyl sulfoxide or mixtures decree GOVERNMENTAL solvents. In the reaction of an epoxide of general formula II, for example 1- (2-carbmethoxy-4,5-dimethylpyrrol-3-oxy) -2,3-epoxypropane, c, piperidine derivative of general formula III, the preferred solvent is ethanol or isopropanol. of general formula II, in which A- (CH2) / 1. cr, for example 1- (2-carbethoxy-4,5-dimethylpyrrol-3-hydroxy) -3-chloropropane, with piperidine derivatives of general formula III, are preferred solvent mi lower aliphatic ketones, cyclic saturated esters such as tetrahydrofuran or dioxane, or dialkyl ormamides, e.g. dimethylformamide, the reaction being carried out in the presence of a catalytic amount of sodium iodide or potassium and a base as an acid acceptor. alkali metal hydroxides, carbonates, bicarbonates, and alkoxides or tertiary organic amines, such as pyridine or trialkylamine, in particular trimethyl l amine or triethylamine, are advisable as an acid acceptor. Of the alkali metal compounds, sodium or potassium compounds are preferably used. The bases are used stoichiometrically. quantity or in insignificant excess. It is also advisable to use an excess, compounds of general formula III, as an acid acceptor. The reaction can be carried out at 70-120s at atmospheric pressure and in a closed vessel — at elevated pressure. The temperature range of 70-120 with due to the choice of solvent. Depending on the temperature, the reaction is usually carried out within 2-15 hours. The product is taken up in usual ways, for example by filtration or by distillation of the solvent from the reaction mixture. The purification of the resulting compound is progressed in the usual manner, for example, by recrystallization from a solvent, salt conversion with an acid or column chromatography. The starting compounds of general formula II are obtained by alkylation of the corresponding 2-carboalkoxy-3-hydroxy-3-hydroxypyrroles with epigylagen hydrin, co-dihalogen-2-propanol or o, c) -dihalopropane. Alkylation of 2-carboalkoxy-3-hydroxypyrrole for the resulting. . starting compounds of general formula II, it is advisable to carry out at 50120 C at atmospheric or elevated pressure. The reaction should be carried out in an inert solvent, for example in a lower aliphatic ketone ,. such as acetone, methyl ethyl ketone or methyl isobutyl ketone, in a lower alcohol, such as methanol, ethanol, propanol or butanol, in a lower alkyl acetate, such as methyl, ethyl or propyl acetate, in a lower dialkylformamide, such as dimethylformamide or diethyl formamide, or dimethylformamide, such as dimethylformamide or diethyl formamide, or dimethylformamide, an excess of alkylating agent that simultaneously serves as a solvent. The reaction is preferably carried out in the presence of a base as an acid acceptor. Suitable bases are carbonates, bicarbonates, alkali metal hydroxides or alkoxides, in particular sodium and potassium,. basic oxides, such as alumina or calcium, organic tertiary bases, for example pyridine, or lower trialkylamines, such as trimethyl or triethylamine. In this case, the bases, in proportion to the alkylating agent, can be used in a catalytic or stoichiometric amount or in an insignificant excess. In the proposed method for preparing the starting compounds, .2-carboalkoxy-3-hydroxypyrroles are preferably reacted with epibromohydrin, 1,3-bromochloropropane, 1,2bromochloroethane, 1,4-bromochlorobutane in acetone, methylisobutyl ketone or dimethylformamide in the presence of potassium carbonate at 50-80 with.
The starting compounds of general formula II with an epoxy group or with a halohydrin structure can be transformed into each other by a simple acid-base reaction.
As a starting compound of general formula II, a mixture of epoxide with halohydrin can also be used, since such mixtures can be formed when the starting compounds are obtained on an industrial scale.
The resulting compounds of general formula I can be salified with a physiologically compatible acid. As commonly used physiologically compatible organic or inorganic; Soy acids use, for example, hydrochloric, hydrobromic, phosphoric or sulfuric, oxalic, maleic, fumaric, lactic, tartaric, block, citric, salicylic, adipic, benzoic and others.
These compounds of general formula and their salts with physiologically compatible acids are pharmacologically active compounds 1 and can be used for the treatment of heart rhythm disorders in the form of tablets, capsules, powders, granules, dragees or solutions.
Getting the original compounds. , Example 1: 3-hydroxy-4,5,6,7-tetrahydro-2-indolecarboxylic acid ethyl ester.
To a well stirred solution of 35 1 sodium in 1.5 liters of ethanol under a nitrogen atmosphere, 284 g of ethyl 2- (ethoxy-carbonylmethylamino) -1-cyclohexenecarboxylic acid E ether 400 ml of ethanol are added dropwise. After boiling for 3 hours, first 600 MP of water and then 150 ml of concentrated hydrochloric acid are added to the cooled solution. After keeping for 6 hours at -10 ° C, the precipitate is filtered off and obtain 142 g of the expected product with T. 94-95 C.
Found,%: C 63.3; H 7.4; N 6,8.
Sy N0MOZ
Calculated,%: with 63.2; H 7.2; N6.7
Example 2. 3-hydroxy-4,5-dimethyl-2-pyrrolecarboxylic acid ethyl ester.
Analogously to example 1, from 35 g of sodium in 1.5 l of ethanol and 264 g of ethyl 3- (ztoxycarbonylmethylamino) -2-methylpropanoic acid in 400 ml of ethanol are obtained from 165 g of ethyl 3-hydroxy-4,5-dimethyl-2-pyrrolcarboxylic acid TPD .
Found,%: C 59.2; H 7.2; N 7.5.
CoHjjNOa
Calculated,%: C 59.0; H 7.1; N 7
Example 3. 3-oxy-4, 5-dimethyl-2-pyrrolecarboxylic acid methyl ester.
Analogously to example 1, from 5.7 g of sodium in 250 ml of methanol and 40 g of methyl 3- (methoxycarbonylmethylamino) -2-methyl-crotonic acid methyl ester in 90 MP of methanol is obtained 28.1 g of methyl 3-o1xy-4, 5-dimethyl2-pyrrolecarboxylic acids with Tn; 170-172p.
Found: C 57.3; H6, b; N 8.4.
szi oz
Calculated,%: C 56.8; H 6.6; N 8.3.
Example 4. Methyl ester of 3- (methoxycarbonylmethylamino) -2-methylcrotonic acid ..
To a well stirred suspension of 50 g of glycine methyl ester chloride in 20 ml of methanol is added first 72 g of a 30% sodium methylate solution in methanol, and
15 min 58 g of ethyl ester of 2-methylacetoacetic acid, then
heated to reflux for 8 hours. The reaction mixture was cooled to room temperature and diluted with 400 ml of dithyl ether and extracted 2 times with shaking (each time with 300 ml of water). The organic phase is dried with magnesium sulfate and concentrated in vacuo. The crude product is subjected to fractional distillation. 47.5 g of the expected product are obtained with T 108-IO C at 0.2 Torr.
Found,%: C 53.9; H 7.5; N 6.9.
CgH, 5N04
Calculated,%: C 53.7; H 7.5; N 7.0.
Example 5. 1- (2-Carboethoxy 4, 5-dimethyl-pyrrole-3-oxy) -2,3-epoxypropane.
100 g of 2 carboethoxy-3-hydroxy-4,5-dimethylpyrrole, 150 g of epibromohydrin and 152 g of dry potassium carbonate are heated in 500 mp of acetone for
16 hours to boiling point. After cooling the reaction mixture, it is poured into 3 liters of ice water, extracted with ether, the collected extracts are washed with 2N. with a solution of caustic solution and water and dried with sodium sulfate. After distilling off the ether and excess epibromohydrin, the residue is extracted with heptane. Obtain 122 g of the desired product with TPA 70-71s.
Found,%: C 60.1; H 7.0; N 6.0. C.2H-iN04.
Calculated,%: C 60.3; H 7.1; N 5.9. Example 6. 1- (2-Carboethoxy 4, 5,6,7-tetrahydroindole-3-oxyl) -2,3 epoxypropane. s
Analogously to example 5 is obtained from 130 ,. g of 3-hydroxy-4 ethyl ester, 5,6,7 tetrahydro-2-indolecarboxylic acid, 170 g of epibromohydrin and 172 g of dry potassium carbonate in 500 ml of acetone 165 g of 1- (2-carboethoxy-4,5,6, 7-tetrahydroindole-3-hydroxy) -2,3-epoxypropane with T „d 102-104s.
Found,%: C63.1; H 7.2; N 5.5.
  ABOUT.. .
Calculated,%: C 63.4; H 7.2; N 5.3
Example 7 1. 1- (2-Carbomethoxy, 5-dimethylpyrrol-3-hydroxy) -2,3-epoxy propane.
Analogously to Example 5, 17 g of 2-carbomethoxy-3-hydro-4,5-dimethylpyrrole, 20 g of epibromohydrin and 2§ g of dry potassium carbonate in 100 ml of acetone and 18.5 g of the desired product with T – d 85-87 ° C are obtained .
Found,%: C 58.5; H 6.7; N 6.5.
c
Calculated,%: C 58.7; Mb, 7; N6,2
Example 8. 1- (2-Carboethoxy-4-butyl-5-methylpyrrl-3-hydroxy) -2.3-. epoxypropane.
Analogously to example 5 of 35 g of 2-carboethoxy-3-hydroxy-4-butyl-5-methylpyrrole, 32 g of epibromohydrin and 41 g of dry potassium carbonate in 100 ml of N, N-dimethylformamide by heating for 8 hours to obtain 41 g of the intended product. m.p. 125-127 ° C.
Found,%: C 64.4; H 8.1; N5.3.
C (5NmM04
Calculated,%: C 64.1; H 8.2; N 5.0
PR and mera 9. 1- (2-Carboethoxy-4-benzyl-5-methylpyrrole-3-hydroxy) -2,3 epoxypropane.
Analogously to example 5, from 20 g of 2-carboethoxy-3-hydroxy-4-benzyl-5methylpyrrole, 14 g of epibromohydrin and 20 g of dry potassium carbonate in 150 ml of methyl isobutyl ketone, 15 g of the desired product are obtained in the form of light yellow, high-viscous oil.
Found,%: C 68.2; H 6.8; N 4.7.
Cig Hji N04.
Calculated,%: C 68.6; H 6.7; N 4,4
Example 10. 1- (2-Carbomethoxy4, 5-dimethylpyrrol-3-hydroxy) -3-chloropropy.
12 g of methyl ester-3-hydroxy-4,5-dimethyl-2-pyrrolecarboxylic acid, 13.8 g of 1/3-bromochloropropane and 13 g of dry potassium carbonate are heated in 50 m of N, N-dimethylformamide for 18 hours to 50 ° C . After cooling, it is filtered, and the filter residue is washed with acetone. The filtrate is extracted with methylene chloride, the organic phase is washed several times with water, dried over sodium sulfate and evaporated under vacuum. The residue is recrystallized from methanol b using activated carbon. Get 9 g. target product with il7-120c. Found:% C 53.9j H 6.7-, N 5.9; With 14.7. .c nbMOZE
Calculated,%: C 53.8; H 6.6; N 5.7) cr 14.4.
Example, ll. 1- (2-Capacity 4, 5-dimethylpyro-3-oxy) -2-chloroethane.
Analogously to Example 10, 12 g of 3-hydroxy-4,5-dimethyl-3-pyrrole-carboxylic acid methyl ester are obtained,
14.2 g of 1,2-bromo-chloroethane and 13 g of anhydrous potassium kap6oHaTa 9.5 g of the target product with 122-123s.
Found,%: C 51.3; H 6.0; N 6.0; 15.6.
C oHldNO., C
Calculated,%: C, 51.8; H 6.1; N 6.1; CE 15.3.
Example 12. 1- (2-Carbomethoxy-4, 5-dimethylpyrrole-3-oxi) -4-chlorobutane.
Analogously to Example 10, 12 g of methyl 3-hydroxy-4,5-dimethyl-2-pyrrolecarboxylic acid, 15.5 g of 1,4-bromochlorobutane and 12.3 g of anhydrous potassium carbonate are obtained from 5.7 g of the expected product, with h: 74- 7bs.
Found,%: C 55.9; H 6.8; N 5.2; C 13.2.
Calculated,%: C 55.5; H 7.0; N 5.4 CE 13.7.
PRI me R 13. (2-Carboethoxy 4, 5-dimethylpyrrole-Z-oxy) -4-chlorobutane
Analogously to example 10 is obtained from
18.3 g of 3 oxy-4,5-dimethyl-2-pyrrolecarboxylic acid ethyl ester, 22.3 g of 1,4-bromochlorbutane and 18 g of anhydrous potassium carbonate 12.5 i; target product with a TPD 58-60 with.
Found,%: C 56.8; H 7.2; N 5.1; CE 12.6.
CoH2oNO qC.
Calculated, ": C 57.0; H 7.4; N 5.1
cr 13.0. .
PRI me R 14. 1- (2-Carboethoxy 4, 5-dimetipyrrol-3-oxy) -3-chloropropane. :
Analogously to example 10, from 18.3 g of ethyl 3-hydroxy-4,5-dimethyl-2-pyProlcarboxylic acid ester, 25 g of 1,3-bromochlorpropane and 18 g of anhydrous potassium carbonate, 11.2 g of the desired product with bO-cc.
Found,%: C 55.2; H 6.7; N 5.1;
cr 13.5.
C H-igNOjCe
Calculated,%: C 55.5; H 6.9; N 5.4 SG 13.7. .
Example 15. 1- (2-Carboethoxy 4, 5-dimethylpyrrole-3-hydroxy) -2-chloroethane
Analogously to Example 10, 18.3 g of 3-hydroxy-4,5-dimethyl-2-pyrrolecarboxylic acid ethyl ester, 20, 5 g of 1,2-bromochloroethane and 18 g of anhydrous potassium carbonate are obtained. 10 g of the desired product with T-pA 81-83 with.
Found,%: C 54.2; H 6.5; N 5.9; SI 14.7.
q-f.
Calculated,%: C 53.8; H 6.5; N 5.7 eg 14.4.
Example 16. l- (2-Kabboethoxy-4, 5-dimethylpyrrol-3-hydroxy).-3-chloropropanol-2. 4.0 g of 1- (2-Capto-ethoxy-4,5-dimethypropyl-3-oxy) -2, 3-epoxypropane are mixed in a mixture of 20 ml of ethanol and 15 m of approximately 4N. ethereal hydrochloric acid. After allowing to stand for 24 hours, the volatile components are distilled off and the residue is chromatographed on silica gel with methylene chloride. 2.7 g of 1- (2-carboxylate-4,5-dimethyl-propol-3-oxy) -3-chloropropanol-2 are obtained. Preparation of compounds of general formula I. Example 1. 24 g (0.1 mol) of 1- (2-carboethoxy-g4, 5-dimethylpyrrole) 2, 3-epoxyprolane and 18 g (0.1 mol) of 4- (2-pyridyl) -piperidin-4- The ol is heated in 20 ml of ethanol for 4 hours at the boiling point. After ethanol is distilled off, the residue is dissolved in a small amount of methanol and ethereal hydrochloric acid is added dropwise. The precipitate formed is filtered off with suction, washed with Diethyl ether and dried. This gives 29 g of ethyl dihydrochloride 3- 2-hydroxy-3 (4-2 -PYRIDYL-4-OXY-E1Iperidino) -propoxy-4,5-dimethylpyrrole-2-carboxylic acid ester (1) with T PA 227-229 C. Output 58.9% Found%: C 53.3; H 6.7; N 8.5; Ct 14.3. N OjCEz Calculated,%: 53.8; H. 6.7; N 8, C "14.5. P p m and m p 2. 55 g (0.23 mol) of 1- (2-carboethoxy-4,5-dimethylpyrrol-3-hydroxy) -2,3-epoxypropane and 41 g (0, 23 mol) of 4-hydroxy-4-phenylpiperidine per The mixture is heated in 600 ml of ethanol for 8 hours to the boiling point. After ethanol is distilled off, the residue is dissolved in a small amount of methanol and the ethereal hydrochloric acid is added dropwise. The precipitate formed is filtered off with suction, washed with ether and dried. 81 g of ethyl 3-2-hydroxy-3- (4-phenyl-4-hydroxypiperidino) -propoxy-4,5-dimethylpyrrole-2-carboxylic acid (2) are obtained with 211-212 ° C. yield 77.5%; Found,%: C 61.2; H 7.1; N 5.9. Cj, Hj5 N20 CfCalculated,%: C 61.0; H7.3; N6,, 8. Example 3. Analogously to Example 1 of 4.0 g (0.015 mol) of 1- (2-car boethoxy-4,5,6,7-tetrahydroindole-Zoxy) -2,3-epoxypropane and 2.8 g (0.015 mol ) 4-hydroxy-4-phenylpiperidi in 50 ml of ethanol gives 5.7 g of ethyl ethyl ester 3-2-hydroxy-3- (4-phenyl-4-hydroxypiperidino) propoxy-4- 5,6,7-tetrahydro-2- indole carboxylic acid (3) with 170-173С. The yield of 78.8%. T Found,%: C 62.7; H 7.6; N 5.5. , C, 5H35Ni0.rCF. Calculated,%: C 62.7; 7.4; N 5.8. Example 4. 50 g (0.2 mol) of 1- (2-carboethoxy-4,5-dimethylpyrrol-3-hydroxy) -3-chloropropane, 35 g (0.2 mol) of 4-hydroxy-4-phenylpiperidine and 50 g of carbonate sodium is heated in 300 ml of N, and-dimethylformamide for 20 hours before. After cooling, the reaction mixture is extracted with methylene chloride and, after evaporation of the organic phase in vacuo, the residue is grown: it is stolen in a small amount of methanol and ethereal hydrochloric acid is added dropwise. The precipitated crystalline is sucked off, washed with ether and dried. 56 g of ethyl ester hydrochloride (4-phenyl-4-oxypiperidine) -proproxy-4, 5-dimethylpyrrole-2-carboxylic acid (4) are obtained with 165-169 C. The yield is 66.4%. Found,%: C 63.2; H 7.7; N 6.7. C-2zH, Nj04Ce Calculated,%: C 63.1; H 7; 5; N 6.4. Example 5. 6.0 g of 1- (2-carboethoxy-4, 5-dimethylpyrrol-3-hydroxy) -3 chloropropanol-2 and 3.5 g of 4-hydroxy-4 phenylpiperidine in 150 ml of dioxane are heated in an autoclave for 15 h to 120 C. After the distillation of the volatile components in a vacuum-highly viscous. the crude product is extracted with ether and 2N sulfuric acid. The aqueous phase is carefully brought to an alkaline reaction 4n. NaOH and then extracted with ether. After drying the organic phase with magnesium sulfate, the solvent is removed, and the residue is dissolved, as described in Example 2, in a small amount of methanol and converted with ethereal hydrochloric acid to ethyl hydrochloride 3-2-hydroxy-3- (4-phenyl). 4-hydroxypiperidino) -propoxy-4,5-dimethylpyrrole-2-carboxylic acid (T) with T 210212 ° C. Yield 32.4%. Analogously to example 2 of the corresponding glycidic esters and 4-hydroxy4-phenylpiperidine or analogously to example 4 of the corresponding 1- (2-carboethoxy-4, 5-dimethylpyrrol-3-hydroxy) chloroalkanes and 4-hydroxy-4-phenylpiperidines in the half of other compounds of general formula I presented in the table. Piperidine derivatives of 4,5 dialkyl-3-hydroxy-pyrrole-2-carboxylic acids esters and their salts in an experiment on animals showed that their effect on arrhythmia caused by .acitin is similar to that of the well-known potent anti-arrhythmic agent N-propylaymalin (compounds 2.11 , 13) or even exceed the effect of the latter (compounds 6, 10, 19). The effect of these compounds compared with N-propylaymalin stronger when applying the maximum allowable doses. N-PropylaiMsTyne increases the duration of infusion of a. Nitrile by a maximum of 174%, and compounds 1.10, 11 and 19 maximum by 324, 347, 308 and 302%, respectively.
The toxicity of the compounds obtained by the proposed method is less than that of H-propyl imalin, with the exception of compound b, which has the same toxicity as H-propylaimulin.
The dosage of the compounds depends on the age, condition and weight of the patient, as well as on the type of application.
The daily dose of active principle is usually 5-100 mg, preferably 10-80 mg.
one

权利要求:
Claims (1)
[1]
The proposed method allows to obtain new compounds that have anti-arrhythmic effect and can be used for treating disorders of the heart rhythm. Formula of the invention. | X0-UHz) m- (H4 “lH2). where R is methyl, butyl, benzyl; R is methyl, or R and R form together - (CHj) 4 -; . R is methyl, ethyl; W and H or OH; R is phenyl, 2-pyridyl, 4-chloro-phenyl, 4-fluorophenyl, 3- (t fluoromethyl) phenyl; , p 0,1,2 and m 1, or their logically compatible salts with acids, is different. It is found that a compound of the general formula II B XO-1H2-A YOOW where R, R and have the indicated values dH-tHgiJi; A is the residue: -CH-CH 0 or - (CH 2) -3 CE, is reacted by the: - piperidine derivative of general formula III -o: where R and R are. in organic dissolved above. at 70-120 ° C, if necessary in the presence of an acid acceptor, and the resulting compound is liberated or salified with a physiologically compatible acid. Sources of information taken into account in the examination 1. USSR Patent No. 522796, cl. C 07 O 211/06, 1973.

类似技术:

---

公开号 | 公开日 | 专利标题

---

PL161379B1|1993-06-30|Method of obtaining 2-|-1-piperazinyl)ethoxy)acetic acid and its dihydrochloride

---

HU226635B1|2009-05-28|Piperidine and piperazine derivatives, medicines containing them as active ingredient and their use

---

EP0400661A1|1990-12-05|Agents for treatment of brain ischemia

---

FR2670491A1|1992-06-19|NOVEL 1,4-DISUBSTITUTED PIPERAZINES, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME

---

PL113879B1|1981-01-31|Process for preparing novel racemic or optically active1-aryloxy-2-hydroxy-3-alkylenaminopropanes

---

SU957768A3|1982-09-07|Process for producing piperidine derivatives of esters of 4,5-dialkyl-3-oxy-pyrrol-2-carboxylic acid or their physiologically compatible acid salts

---

SK164297A3|1998-09-09|1,6-disubstituted isochromans for treatment of migraine headaches

---

DD298911A5|1992-03-19|AZETIDINES, THEIR PREPARATION AND USE AS INTERMEDIATE PRODUCTS FOR THE MANUFACTURE OF BIOLOGICALLY ACTIVE SUBSTANCES

---

KR920002295B1|1992-03-21|Process for the preparation of pyrrolidone derivatives

---

SU578884A3|1977-10-30|Method of preparing triazoleisoindole derivatives

---

FI61693C|1982-09-10|ANALOG OF FARMING FOR PHARMACEUTICAL ACTIVITIES

---

US3574749A|1971-04-13|1-|-3-amino-2-propanol derivatives

---

EA021810B1|2015-09-30|Inorganic salt complexes of vildagliptin

---

SU499801A3|1976-01-15|Method for preparing derivatives of diphenylmethoxyethylamino compounds

---

KR840001775B1|1984-10-19|Process for preparing hetrocyclic derivatives

---

EP0053017B1|1985-02-20|Amide derivatives

---

ES2228884T3|2005-04-16|NEW DERIVATIVES OF IMIDAZOL.

---

SU812174A3|1981-03-07|Method of preparing cis-4a-phenyloctahydro-1h-2-pyrindine derivatives or their sal lts

---

US3972994A|1976-08-03|Disubstituted azabicycloalkanes

---

CA2148693A1|1994-05-11|Tartronic acids, their acetalic ethers and o-esters

---

SU670216A3|1979-06-25|Method of producing derivatives of oxime or samts thereof

---

EP0301549A1|1989-02-01|1-[2-|phenyl]-piperazine compounds, a process for preparing them and pharmaceutical compostions containing them

---

SU507241A3|1976-03-15|The method of obtaining derivatives of theophylline

---

SU586835A3|1977-12-30|Method of preparing aminopropanol derivatives or their salts,racemates or optically active antipodes

---

Kornet1967|Synthesis of 1‐methylpyrazolidine and some of its derivatives

同族专利:

---

公开号 | 公开日

---

HU184936B|1984-11-28|

---

AU532982B2|1983-10-20|

---

ZA806282B|1981-10-28|

---

ES495831A0|1981-11-01|

---

EP0027928A2|1981-05-06|

---

DE2941597A1|1981-04-23|

---

JPS648632B2|1989-02-14|

---

JPS5663956A|1981-05-30|

---

YU262380A|1983-01-21|

---

IL61212A|1983-09-30|

---

AT2746T|1983-03-15|

---

IE50796B1|1986-07-23|

---

IL61212D0|1980-12-31|

---

AU6320480A|1981-04-16|

---

DK430380A|1981-04-14|

---

EP0027928B1|1983-03-09|

---

ES8200363A1|1981-11-01|

---

NO803047L|1981-04-14|

---

EP0027928A3|1981-05-20|

---

US4315939A|1982-02-16|

---

CA1155124A|1983-10-11|

---

FI70013B|1986-01-31|

---

DE3062300D1|1983-04-14|

---

FI802960A|1981-04-14|

---

FI70013C|1986-09-12|

---

CS214759B2|1982-05-28|

---

IE802102L|1981-04-13|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

FR1527E|1902-08-20|1903-08-12|Hermann Hilbert|Process for extracting gelatin and glue from bones|

---

DE1720033A1|1966-03-02|1971-05-19|Yoshitomi Pharmaceutical|New indole derivatives and processes for their preparation|

---

CH481104A|1967-01-25|1969-11-15|Geigy Ag J R|Process for the production of new indole derivatives|

---

US3860609A|1969-05-27|1975-01-14|Novo Terapeutisk Labor As|3-aminoalkyloxyindoles|

---

DE2630152A1|1976-07-05|1978-01-19|Cassella Farbwerke Mainkur Ag|-Phenoxy-hydroxypropyl 4-pyridyl-piperidinol derivs. - useful as antiarrhythmic agents|EP0076072B1|1981-09-24|1987-05-13|BEECHAM - WUELFING GmbH & Co. KG|Sulphonamides|

---

US4558129A|1983-05-18|1985-12-10|SyntexInc.|Benzodioxanyl-hydroxyethylene-piperazinyl acetanilides which effect calcium entry and β-blockade|

---

US4567264A|1983-05-18|1986-01-28|SyntexInc.|Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry|

---

CN1315830A|1998-07-27|2001-10-03|伊莱利利公司|Treatment of anxiety disorders|

---

US6242450B1|1998-07-27|2001-06-05|Eli Lilly And Company|5-HT1F antagonists|

---

UY33388A|2010-05-17|2011-12-01|Glaxo Group Ltd|NEW PROCESSES FOR THE PREPARATION OF PIRIMIDINONE COMPOUNDS|

法律状态:

优先权:

---

申请号 | 申请日 | 专利标题

---

DE19792941597|DE2941597A1|1979-10-13|1979-10-13|PIPERIDE DERIVATIVES OF 4,5-DIALKYL-3-HYDROXY-PYRROL-2-CARBONIC ACID ESTERS, THEIR PRODUCTION AND THE PHARMACEUTICAL PREPARATIONS CONTAINING THEM|

---