• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    3-(1-piperidinylalkyl)-4H-pyrido[1,2-a pyrimidine-4-one derivs. and their acid addn. salts are prepd. by reacting compds. of formula (IV) with compds. of formula (V). In the formulas, R1 and R2 are H, lower alkyl, lower alkoxy, halo or CF3; R3 is H, lower alkyl or aryl; Alk is lower alkylene; R is H, lower alkyl, OH, lower alkoxy or CH2-OH in the 2-, 3- or 4-position of the piperidine ring; L is lower alkoxy, OH, halo, amino, mono- or di-(lower alkyl) amino; Q is -x-Ar; x is C=O, CHOH, CHOC(=O)Ra, or C=N-NH2; Ar is aryl; and Ra is H or lower alkyl. (I) are useful as potent serotonin antagonists for anticongestive use.
    公开号:SU1093251A3
    申请号:SU823372597
    申请日:1982-01-12
    公开日:1984-05-15
    发明作者:Эдмон Жозефин Кеннис Людо；Каролюс Мертенс Жозефин
    申请人:Жансен Фармасетика Н.В. (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to new biologically active compounds derived from 4H-pyrido (1,2-a) pyrimidine-4-one or their pharmaceutically acceptable acid addition salts, which can be used in medicine.  A known method for producing prod.  4H-pyrido (1,2-a) pyrimidin-4-ones containing in the 3rd position an aminoalkynyl s 4titel ttl) by alkylating amines 3-hal-4H-pyrido (1,2-a) pyrimidin-4-ones .  The chain of the invention is the preparation of new compounds - derivatives of 4H-pyrido (1,2-a) pyrimidits-4-one or their pharmaceutically acceptable salts, which have interesting pharmacological properties.   The goal is achieved by the fact that according to the method of producing 4H-PYRIDO (1,2-a) pyrimidine-A-one, of the general formula WyCH, k-Nyi-CHz-CHrlJ, where R is hydrogen or methyl; R.  2 — hydrogen, methyl, chlorine, or their pharmaceutically acceptable acid addition salts are reacted with 4H-pyrido (1,2-a) pyridin-4-one with the general formula CH2-CH2-Hal with piperidinyl derivatives of the formula in the presence of a base in inert an organic solvent, preferably at the boiling point of the solvent, followed by isolating the desired product as a base or salt.  BUT.  Obtaining intermediate products.  Example 1  To a mixture consisting of 20 h.  sodium methoxide and 160 h of methanol were added 50 hours with stirring.  2-thiophene acetonitrile and then drop by drop 66 hours.  1- (fensch1methyl) -4-piperidinone.  The mixture thus obtained is heated by refluxing and stirring at the temperature of refluxing for 1 hour.  This reaction mixture is cooled and evaporated.  The residue is distilled on a molecular distillation unit.  The result is 70 hours  (Phenylmethyl) -4-piperidinylidene-1-2-thiopheneacetonitrile as residue.  Similarly, 4-methyl-c -fl- (phenylmethyl) -4-piperidine ylidene-3 benzene-acetonitripe, m. square  193.4 ° C.  Example 2  A mixture consisting of 70 h.  o1-C1- (phenylmethyl) -4-piperidinylidene -2-thiopheneacetonitrile in 800 hours  methanol, subjected to hydrogenation at normal pressure and at room temperature from 10 h.  10% catalyst - palladium on charcoal.  After entering the calculated amount of hydrogen, the catalyst is filtered off and the filtrate is evaporated.  The result is 70 hours  the residue is 1- (phenylmethyl) (2-thienyl) -4-piperidineacetonitrile.  In a similar way, (4-methylfensh1) -4-piperidineacetonitrile was obtained as a residue.  Example H. To a mixture consisting of 74 h.  (4-methylfensh1) -4-piperidineacetonitrile, 95.4 h.  sodium carbonate, several crystals of potassium diode at 1840 h.  4-metip-2-pentanol, added in portions of 39.21 parts.  (chloromethyl) benzene.  The resulting mixture is subjected to stirring and defpegmirovaniya within 24 hours  The reaction mixture is cooled and 400 hours are added.  water.  Organic layer. separated, dried with potassium carbonate, filtered and evaporated.  The oily residue is dissolved in 1,1-oxybisethane and hydrogen chloride gas is introduced into the resulting solution.  The precipitated salt, the hydrochloride salt, is filtered off and dried.  Yield: 68 hours  di-c | b- (4-methylphenyl) -1- (phenylmethyl) -4-piperidineacetonitrile, t. square  212-210 0.  Example 4 To a stirred mixture consisting of 29.6 h.  1- (phenylmethyl) -cL- (2-thienyl) -4-piperidineacetonitrile in 100 hours.  dimethyl sulfoxide, add in parts 4 hours.   sodium hydride and continue stirring during the night.  The reaction mixture is poured into water, the precipitated product is filtered off and extracted with trichloromethane.  The extract is dried, filtered and evaporated.  The residue is crystallized from 2,2-oxy-bis-propane.  Yield: 10 hours  (35%) of 1- (phenylmethyl) -4-piperidine - (2-thienyl) methanone, t. square  100,.  Similarly, (4-metshphenyl) -C1- (phenylmethyl) -4-piperidinyl methanol, t. square  83 , 9 ° C.  Example 5  K5h  add 2.18 h.  1,2-dibromoethane and a small amount of iodine to initiate the reaction.  Next, a solution consisting of 28 h is added dropwise.  4-chloro-1-methylpiperidine in 180 hours  tetrahydrofuran, at which time the reaction mixture is heated to 70 ° C.  After cooling, a solution consisting of 14 hours of 3-methylbenzonitrile in 90 hours is added dropwise.  tetravvd rofurana.  Stirring is continued for another 1 h, at the temperature of refluxing.  The reaction mixture is cooled and injected into a solution consisting of 75 hours.  ammonium chloride in water.  The product is subjected to extraction with 2,2-oxibispropane.  The extract obtained is washed with water, dried, filtered and evaporated.  The result is 35 hours  (3-Meth1phenyl) - (1-methyl-4-piperidinyl) methanol as an oily residue.  Example 6  K7h  magnesium is added dropwise a solution consisting of 50 h.  1-bromo-2-methylbenzene in 140 h.  1,1-oxybisethane.  The mixture obtained in this way is deflated.  The mixture is then stirred for 15 minutes while refluxing. The Grignard complex is cooled down and added dropwise to a solution consisting of 30 h.  1- (fensch1methyl) -4-piperidinecarbonitrile at 70 h. .  , Example 8.  A mixture consisting of 12 h.  ethylcarbochloride, 31 h.  (2-Methylphenyl) -C1- (phenipmethyl) -4-piperidinylZmetanone and 270 h.  dimethylbenzene, mix and defpegmie within 4 hours. then this mixture is evaporated and the residue is dissolved in 3 chloromethane.  The resulting solution is washed with a dilute hydrochloric acid solution.  The organic phase is separated, dried, filtered and evaporated.  The result was 20 hours  ethyl 4- (2-methylbenzoyl) -1-piperidinecarboxylate as an oily residue.  Example 9  Using a procedure similar to Example 8, and using equivalent amounts of the corresponding starting materials, the following materials were also obtained: ethyl 4- (2-thienylcarbonyl) -1-piperavdincarboxylate as a residue; ethyl 4- (4-metsh1benzosh1) -1-piperidinecarboxylate in the form of a residue; ethyl 4- (4-fluorobenzoyl) -4-methyl-1-piperidinecarboxylate as a residue.  Example 10  To a stirred mixture consisting of 35 h.  (3-methylphenyl) - (1-methyl-4-piperidinyl) methanoate, 1 h.  sodium carbonate and 225 h.  dimethylbenzene is added dropwise 22 hours.  ethylcarbonate at 20 C.  The stirring process is continued for another 6 hours at the reflux temperature.  The reaction mixture was evaporated to give ethyl 4- (3-methylbenzoyl) -1-piperidinecarboxylate (12 h. ) in the form of oil.  Ethyl 4- (4-bromobenzoyl) -1-piperidinecarboxylate is prepared in the same way.  Example 11  A mixture consisting of 103 h.  ethyl 4- (4-metsh1benzoyl) -1-piperidinecarboxylate and 900 h.  48% solution of hydrobromic acid in water, mix and reflux for 3 hours.  The reaction mixture is stirred further, cooled in an ice bath, the precipitated product is filtered off, the precipitate is washed with water and 2-propanone.  Poluchtsot 4-methylphenyl- (4-piperidinip) methanone hydrobromide (91 h. , 86%), T. square  300 ° C.  Example 12  Using the procedure of hydrolysis, similar to example 11, receive: (3-Metshphenyl) - (4-piperidinyl) methanone hydrobromide; (4-bromphensh1) - (4-pipvridinil) IU. anon hydrobromide; (2-methylphenyl) - (4-piperidinyl) methano and hydrobromide; (4-piperidi1psh) - (2-tnen1sh) methanone hydrobromide and (4-fluorophenip) - (4-methyl-4-piperidinyl) methanone hydrobromide.  Example 13  A mixture of 3.8 h.  3- (2-chloroethyl) -2,8-dimesh1-4H-ShFIDO (1,2-a) pyrimidin-4-one; 3h  3- (4 pipervdinyl) -1H-indoles; 10 h.  sodium carbonate; 0.1 hour  di $. 10 potassium iodide and 240 h.  4-methyl-2-pentenone, refluxed with constant stirring for 20 h.  The reaction mass is filtered in a hot state through Well 1o, the filtrate is evaporated.  The residue was purified by chromatography on a column filled with silica gel. A 1 mixture consisting of trichloromethane and methanol (90:10 by volume) was used as eluent. The combined fractions are collected, and the eluate is evaporated. The residue is crystallized from a mixture consisting of 2-propanol, 2,2-oxybispropane and 4-methyl-2-pentanone.  (7H-indol-3-yl) -1-piperidinyl, 8-dimetip-4H-pyrido (1,2-a) pyrimidin-4-oi is obtained (h. ), t pl.  235,  Example 14  Using the method of Example 13 and using equivalent amounts of the corresponding starting materials, the following are obtained: 3-t2-t4- (1H-indol-3-yl) -1-piperidinylDethyl -2,7-dimesh1-4H-pyrido (1.2 -a) pyrimidin-4-OH, t. square  203.7 ° C; 7-chloro-3- 2- 4- (1H-indol-3-yl) -1-piperidinylO ethyl -2-methyl-4H-pyrido (1,2-a) pyrimidin-2-one, t. square  240.9С; 3-C2-t4- (1H-indol-3-yl) -1-piperi dinyl} ethyl:} - 2,6,8-trimetnl-4H-pyrido (1,2-a) pyrmidine-4-one, t . square  223.4 7-bromo-1-t2- 4- (1H-indole-3-ip) -1-piperidinyl ethyl -2-metsh-4H-pyrido (1,2-a) pyrimidin-4-one, t. square  224 ,.  Example 15  A mixture of 4.8 h.  3- (2-chloroethane) -2,6-dimesh-1 -4H-pyrido (1i 2-a) pyrimidin-4-one; 4 hours  3- (4-piperidinyl) -1H-indoles; 8.5 hours  sodium carbonate and 120 h.  4-methyl-2-pentatone, subjected to stirring and refluxed overnight using an aqueous separator.  The reaction mixture is cooled, water is added, and the precipitated product is filtered off.  But it is dissolved in a mixture consisting of trichloromethane and ethanol (90:10, volume fraction).  The resulting solution (Filter on silica gel and the filtrate evaporated.  The residue is crystallized from 2-propanol.  Yield 2.5 hours  (31%) 3-C 2- (4-indole-3-yl) -1-piperidinyl etyl J-2,6-dimethyl-4H-pyrido (1. 2-a) -pyrimidin-4-one, t. square  224.9 C.  . -.  Example 16  Using the procedure of Example 15 and using equivalent amounts of the corresponding starting materials, 3-t2-t4- (tH-indole-3-yl) -1-piperidinyl} ethyme is obtained; ) -2-methyl-AN-pyrido (1,2-a pyrimidin-4-one.  .  Pr and bj e p 1.  1 hour .  7-bromo-3-2 (4-indole-3-yl) -1-piperidinyl eyl-2-methyl-4H-pyrido (1,2-a) pyrimidin-4-one at 80 h.  The acetonitripe is heated, then acidified with 2-propiol and made with hydrogen chloride.  With stirring, the product is subjected to crystallization.  It is filtered and dried to obtain 1.2 h.  . . . . “. “.   . . w -, -.  ,  , 7-bromo-3 - (; 2- {4- (1H-indole-3-Sh1) -1-piperidine) dihydrochloro-nd; -2-methyl-4H-pyrido (1,2-a) pyrimidin-4-one , t square  227.9-234, (decomp. ).  In a similar manner, dihydrochloride-3-G2-14-1H-indol-3-yl) -1-piperidinyl ethylZ-2, 8-dimethyl-4H-pyrido (1,2-a) pyrimidin-4-one (t. square  282, a) and dihydrochloride (1H-indol-3-yl) -1-piperidinyl-atsh1 -2, 7-dimethyl-4H-pyrido (1,2-a) pyrimidin-4-one (t. square  250,1259,).  Biological tests of the described 4H-pyrido (1,2-a) pyrimidin-4-one derivatives and their salts have been carried out.  Test 1.  Antagonistic activity towards serotonin in the caudal (caudal) artery in rats.  Caudal arteries taken from males weighing 210-235 g were used in accordance with the experiment.  Two spiral strips 5-6 cm long and 2 mm wide, obtained from each artery, are placed vertically in an organic bath with a capacity of 100 ml filled with oxygenogenic Kreps-Henseleit solution (Kreps-Heuseleit).  Submaximal contractions of the arterial strips are induced by adding single doses of serotonin (40 g / ml) to the organic bath for 2 minutes and 10 minutes after each addition.  The amplitude of the contraction is measured before and after five minutes of the addition of the preparation.  After washing, the antagonist is added again three times in order to check for stock.  wounded if normalized; the contraction of the column in the table shows the value of ng / ml for a series of compounds characterized by formula (1) in the indicated experiment.  The value of ED50 indicates the minimum concentration of preparations for the radio, which remove the amplitude of contractions by at least 50% relative to the normal value.  Test 2.  A study in gastric diseases.  Diseases caused by compounds 48/80.  Compound 48/80 (a mixture of oligomers obtained by condensation of 4-methoxy-L-methylbenzene of tanamine and formaldehyde) is a potential agent for the release of vasractive amines from endogenous sources, such as, for example, histamine and serotonin.  In rats that have been given compound 48/80, significant changes in blood flow in various vascular layers are observed, cyanosis (cyanosis) of the ears and limbs is observed within five minutes after the injection of the compound and 30 minutes later the rats die from shock.  If rats pre-weight.  As a classic HI antagonist, shock and subsequent death can be avoided.  However, the stimulating effect on gastric secretion was not suppressed in this way, and rats treated with 48/80 and protected with a 1H shock antagonist can have all the signs of intensive gastric gland activity: autopsy is significant, indicating abdominal distension with abnormal contents and strong - red spots on the entire mucous membrane corresponding to the areas on the destroyed glands.  A number of well-known serotonin antagonists, such as, for example, methysergide, cyproheptadine, cicarisle, pipamperone, spiperone, pizothyphene, teregoline, completely interfere with cyanosis (sinyukhe) of the ears and extremities, as well as the diseases of the joints. fat and abnormal abdominal distension.   Method.  Males of Wistar rats born from parents of kinship with each other weighing 220-250 g were kept without food for 16 hours, and water was given to them without restriction.  The compounds to be tested were administered orally as a solution or suspension in a liquid medium.  A control rat and neat received a compound subjected to 1 After one hour 5-C4 tests - (diphenylmethyl) -piperizinip-methyl -1-methyl-1H-benzimidazol-2-methanol was administered subcutaneously to all rats in an amount of 2.5 mg / kg live weight .  Two hours after the oral administration of the compound to be tested, compound 48/80 (freshly dissolved in water at a concentration of 0.25 mg / ml) was administered intravenously to all rats (dose 1 mg / kg), with the exception of pure rats.  Four hours after the intravenous injection of the 48/80 compound, the rats were decapitated and their stomachs were removed.  Next, the jules were examined for swelling and content (blood, liquid, food) and thoroughly washed.  Macroscopic lesions were assessed on a scale from O to, with O corresponding to the complete absence of permanent lesions, and the highest score corresponds to the red spot covering more than half of the gland surface.  The second half of the table refers to compounds characterized by formula (1) and doses (in ng / kg body weight) for which abdominal distension, as well as diseases in the gastric gland area, is completely absent in 50% of the rats studied (t. e.   value).  The proposed compounds completely prevent damage to organs or tissues, which is caused by excessive serotonin cleavage, and also block serotonin-induced contractions of bronchial tissues and blood vessels, arteries, and veins.  Therefore, the proposed compounds may be used to treat gastrointestinal ulcers, bronchial spasms, hemorrhoids, vakises, and similar diseases, all of which are caused by hyperemia. From the point of view of their valuable anti-hypereminal properties, the proposed compounds can be prepared in different pharmaceutical forms to be taken methods For the preparation of pharmaceutical compositions, an effective anti-hyperemina amount of a characteristic compound in the form of a base or an added acid salt lots, which is the active ingredient, are thoroughly mixed in a mixture with a pharmaceutically acceptable carrier. The latter may have a wide range of different forms depending on the form of preparation required for administration.  These pharmaceutical compositions are preferably administered in a unitary dosage, i.e., e, in a form suitable preferably for oral administration, for rental or for parenteral injection.  For example, in preparing the compositions in a form suitable for oral administration, any of suitable pharmaceutical agents can be used, such as water, glycols, oils, alcohols, and the like; No, if liquid oral preparations are used, for example suspensions, syrups, elixirs and solutions, or solid carriers, for example starches, sugars, kaolin, lubricants, binding agents, disintegrating agents and the like, in the case of preparing powders, capsules and tablets Because of the ease of taking the pill, the capsule is the most convenient unit form for oral administration and in this case it is advisable to use solid pharmaceutical carriers.  For parenteral compositions, the carrier may be sterile water, at least not a large part, although other ingredients, for example, solubilizing agents, may be administered.  Injection solutions, for example, can be prepared in such a way that the carrier in them is a salt solution, a glucose solution or a mixture of a salt solution and a glucose solution.  Injectable suspensions may also be prepared, in which case suitable liquid carriers, suspending agents and the like may be used.  The acid addition salts, due to their increased solubility in water compared to the corresponding basic formulas, are obviously more suitable for the preparation of aqueous compositions.  Particularly preferred is the preparation of said pharmaceutical compositions in unit dosage form for ease of administration and uniformity of dosage.  The dosage unit form of the present invention refers to physically discrete elements suitable for use as a unitary dose, and each element contains a predetermined amount of active ingredient calculated to provide the desired therapeutic effect in combination with the required pharmaceutical carrier.  Examples of such dosage unit forms are tablets (including notched, grooved and coated tablets), capsules, pills, bags of powders, wafers, injection fluids or suspensions, full teaspoons, full tablespoons, etc, and their segregated compound complexes.  Although the amount of active ingredient to be administered to a patient can vary widely depending on typical circumstances, such as the nature and severity of the diseases, doses from about 0.005 to about 1 mg of the active ingredient per kilogram of live weight should be approximately from 0.01 to about 0.50 mg per kilogram of live weight, administered either simultaneously or repeatedly, are generally satisfactory.  Exemplary exemplary anticonvulsant pharmaceutical compositions in unit dosage forms are suitable.
    to systematically enter humans and animals in accordance with the invention. These examples are given for the purpose of illustration and do not limit in any way the scope of claims of the proposed invention.
    Drops for oral administration.
    50 liters of solution are obtained for use as drops for oral administration containing 10 mg of 3-C2 -2- (4-fluorobenzoyl) -1 -piperidinyl J-sf or J-2-methyl-4H-pyrido (1,2-a ) pyrimidine 4-OHa as active ingredient (A.1) per milliliter.
    The solution contains:
    А.1., Г500
    2-hydroxypropanoic acid, Lo 5.
    Saccharin sodium, g 1750 Cocoa, l2,5
    Purified water, l 2.5 Polyethylene glycol is added to a total volume of 50 liters.
    The active ingredient is dissolved in 2-hydroxypropanoic acid and 1.5 liters of polyethylene glycol at a temperature of 60-80 ° C. After cooling to 30-40 ° C, 35 liters of polyethylene glycol are added and the mixture thus obtained is thoroughly mixed. Then the sodium saccharin solution is added 2.5 liters of purified water and, while stirring, add more cocoa and polyethylene glycol to the full volume. The solution obtained in this way is poured into the required containers.
    Oral solution. Prepare 20 liters of oral solution containing 20 mg of (4-fluorobenzosh1) -1-piperidinyl eth1-2-methyl-4H-pyrido (1,2-a) pyrimidin-4-in as the active ingredient (A. 1) per teaspoon (5 ml).
    The solution contains: A. 1., g20,
    2,3-Dioxybutadionic acid, g 10 Saccharin sodium, g 1,2,3-Propentriol, l 12
    Sorbitol, 70%
    solution, l3
    Methyl 4-hydroxybenzoate, g9 (, Propyl 4-hydroxybenzoaTj g1
    Malinova Essenti, MP2
    Essenzi gooseberry, ml2
    Purified water is added to a total volume of 20 liters.
    Methyl 4-hydroxybenzoate and propyl 4-hydroxybenzoate are dissolved in 4 liters of boiling purified water. 2,3-Dioxy-butadionic acid is dissolved in 3 liters of the solution thus obtained, and then the active ingredient. The latter solution is mixed with the remaining part of the first solution and 1,2,3-propantriol and sorbitol solution are added. The sodium saccharin solution is dissolved in 0.5 liters of water and then raspberry extract and gooseberry extract are added. The latter solution is mixed with the first and water is added to the full volume. The solution thus obtained is bottled in the required containers.
    Capsule preparation.
    1000 capsules are prepared, each containing 20 mg of 3-t2-4- (4-fluorobenzoyl) -1-piperidinyltil -2,4-metsh1-4H-pyrido (1,2-a) pyrimidin-4-one as active ingredient (A.O. Capsule contains, g:
    A.1.20
    Sulfate lurila
    rub 6
    Starch56
    Lactose56
    Colloidal dioxide
    silicon 0.8
    Magnesium stearate 1,2
    This composition is obtained by thoroughly mixing the above ingredients. The mixture thus obtained is packaged in hard gelatin capsules.
    . Preparation of film coated tablets
    YuOOi solid tablets, each of which contains as active ingredient 10 mg of 3-t2- 2- (4fluorobenzoyl) -1 -piperidinyl | ethyl-, -methyl-4H-pyrido (1,2-a) pyrimidin-4-one, obtained from the following preparation, rt.
    A.t.100
    Lactose570
    Starch200
    Polyvinylpyrolidone (Kollidon
    K-90) 10
    Microcrystalline, garlic cellulose
    (Avitsel) 100
    Dodecyl sulfate
    rub 5
    权利要求:
    Claims (1)
    [1]
    The method of obtaining 1 derivatives of 4H-pyrido (1,2-a) pyrimidin-4-one of the general formula where Ry is hydrogen or methyl;
    Rj is hydrogen, methyl, chlorine or bromine, or their pharmaceutically acceptable acid addition salts, which are characterized in that 4H-pyrido (1,2-a) pyridin-4 — one of general formula 11 is reacted cm 3
    CH 2 -CH 2 -Hai with a piperidinyl derivative of formula 11 in the presence of a base in an inert organic solvent, at the boiling point of the solvent, followed by isolation of the target product in the form of a base or salt.
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    同族专利:
    公开号 | 公开日
    JPH0215550B2|1990-04-12|
    PL230364A1|1982-03-29|
    PL233902A1|1982-07-19|
    ZA812085B|1982-11-24|
    KR850000412B1|1985-03-26|
    JPS56150091A|1981-11-20|
    PL132428B1|1985-03-30|
    KR830005220A|1983-08-03|
    KR850000413B1|1985-03-26|
    PL131162B1|1984-10-31|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    JPH0615529B2|1985-04-01|1994-03-02|エーザイ株式会社|Novel piperidine derivative|
    EP0335442B1|1988-03-28|1996-05-15|Janssen Pharmaceutica N.V.|Agents for preserving or restoring the soundness of the skin|
    WO2009108798A1|2008-02-29|2009-09-03|Vm Discovery Inc.|Method for treating pain syndrome and other disorders|
    PL2812004T3|2012-02-10|2019-01-31|Ptc Therapeutics, Inc.|Compounds for treating spinal muscular atrophy|
    MX2018007022A|2015-12-10|2018-11-12|Ptc Therapeutics Inc|Methods for treatng huntington's disease.|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US13484580A| true| 1980-03-28|1980-03-28|
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