• 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:
    Compounds of the general formula: <IMAGE> I in which alk and alk' represent the bivalent radicals; aliphatic alkyl chains; and R and R' represent the alkyl, halogen, hydrogen, alkyloxy, -OH, -CF3 or -SCH3 radicals. Said compounds of the formula I are effective and useful as antiglaucomic and antipsychotic agents and also as additive agents in the withdrawal treatment of various addictive conditions. Methods for their preparation are also disclosed.
    公开号:SU852174A3
    申请号:SU792753553
    申请日:1979-04-17
    公开日:1981-07-30
    发明作者:Сильвестрини Бруно；Байокки Леандро
    申请人:Ациенде Кимике Риуните Анджелинифранческо A.C.P.A.Ф.C.П.A (Фирма)；
    IPC主号:
    专利说明:

    (54) METHOD FOR OBTAINING CYCLO-ALKYLTRIAZOLES The invention relates to the synthesis of derivatives of cycloalkyltriazoles and can be used in medicine. A method is known for producing triles by the interaction of hydrazines with lactams l. The aim of the invention is synthesizing biologically active derivatives of cycloalkyl triazoles. This goal is achieved by the method of producing cycloalkyl triazoles of the general formula (pfzW R I. I (where n is 2 or 3, m is 4 or 5, and each of R and R is selected from the group including hydrogen, methyl, chlorine, or their salts, which consists in that the arylpiperazine alkanoic acid hydrazide of the formula Ut / L is cis p-sssshg "- / OR THEIR SALTS where R, R and p have the above values, is heated with the compound of the formula xlCHi) m. / (CHzlm, (III" ( S OAIKCH Target products are made in the form of a base or salt by known methods. Non-toxic and pharmaceutically acceptable salts of the proposed All salts that are commonly used to form salts with basic substances used as pharmaceutical substances, for example, salts with monobasic or polybasic mineral acids (hydrochloric, sulfuric, phosphoric, etc.) and salts with polycarboxylic or polycarboxylic organic acids ( maleic, lactic, methanesulfonic, acetic, glyconic, pamic acid, etc.). These salts are prepared using conventional techniques starting from a pharmaceutically acceptable acid and a selected active base. Some of these salts may be products of one or two molecules of acid, some are crystallized in either anhydrous or hydrated form, and in some cases may retain one or more crystallized solvent molecules. The heating of the hydrazine of formula II and lacto1Ma can be carried out in the presence or absence of a solvent. In some cases, the presence of a basic crystallizer, such as sodium methyl, accelerates the reaction. During heating, alcohol is first released and an amidrazone is formed, which is not absorbed, and subsequently water is precipitated to close the triazole ring. The reaction can be carried out either by removing alcohol and water, which are formed during the reaction, or by conducting the reaction under reflux conditions. Example 1. Preparation of (2-tolyl) -1-piperazinylZ propyl-5, 6,7, 8-tetrahydro-5-triazole-- (4,3-a) pyridine (formula I, p 3, m 4, R 2 -CHi; R-H). A mixture of 27 g (0.147 mol) of 1- (2-tolyl) -piperazine, 23 g (0.154 mol) of ethyl 4-chlorobutyrate. 11 g (0.104 moles of anhydrous sodium carbonate and 130 ml of absolute ethanol are heated to reflux distillation with stirring for 24 hours. The reaction mixture is cooled to a crystalline temperature and the sodium chloride formed is removed by filtration. The alcohol is removed from the filter by heating under reduced pressure and pure residue is distilled to give 20 g (47%) of 4- (2-tolyl) -piperazinyl butyric acid ethyl ester with a boiling point of 185 ° (0.6 mm Hg. ), which is dissolved in 50 ml of absolute ethanol. To the solution is added 15 g of hydrazine hydrate (99%) and the resulting solution is heated under reflux for 4 h. The alcohol is then removed under a lower pressure of 1HT and the residue is dissolved in 50 ml of a solution of 50% potassium carbonate. It becomes a low melting point filtered solid, which is collected and washed with water and ether (14 g - 74%). A small part is converted into the hydrochloride salt with mp 202 ° C after crystallization from absolute ethanol. 14 ( 0.05 mole of the above hydrazine is mixed with 6 g (0.05 mole) of o-methylvaleriolactam, About 4 g of dry sodium methoxide and, mixing, heated at 120-130 ° C for 45-50 minutes. The mixture is cooled and dissolved in absolute ethanol. Insoluble impurities are removed by filtration and the filtrate is treated with an excess of a solution of hydrochloric acid in ethanol. The precipitate that forms is removed by filtration, and recrystallized from ethanol at 95 ° C, m.p. 266 ° C, yield 16 g (73%). Sao 29 5-2HC1. Example 2. Preparation of (2-tolyl) -1-piperazinyl ethyl} -7, 7, -8, 9-tetrahydro-5H-5-triazole (4,3-a) azepine (n 2; me5; R 2- SNO; R N). a) Hydrazide 4- (2-tolyl) -piperazinyl propionoric acid. A solution of 28.4 g (O, 103 mol) of ethyl 4- (2-tolyl) -piperazinyl-propionic acid and 27 g (0.5 mol) of hydrazine hydrate (99%) in 50 ml of ethanol is heated under reflux for 5 The solution is then cooled, diluted with three volumes of water and the solid, which is separated, removed by filtration and recrystallized from ethyl acetate. Yield 13.8 g (51%), m.p. 138-139 ° C. b) A mixture obtained by mixing 4.3 g (0.034 mol) of o-methyl caprolactam, 9 g (0.034 mol) of the hydraeid described above and 0.9 g of sodium methoxide is heated with vigorous stirring with an oil bath at 160170 - s for 1 h 15 min. After cooling, a portion soluble in boiling hexane is extracted from the residue using three successive washes and decantations. Hexanor extracts are combined and evaporated to dryness. The residue is dissolved in ether and a double equivalent of hydrochloric acid in ether is added to it. Dihydrochlo-. The REED that precipitates is collected by filtration and recrystallized from ethanol, m.p. 252-s, yield 11 g (77.5%). C oa 2HC 1 (g Example 3. Preparation of .4- (2-tolyl) -1-piperazinyl-ethyl-5, 6,7,8-tetrahydro-5-triazole- (4,3-a) pyridine (n 2 —SHa; RH). A mixture of 23.1 g (0.22 mol) of o-methylvalerolactam, 52.4 g (0.19 mol) of 4- (2-tolyl) -piperazinyl-propionic acid hydrazide and 200 ml of xylene is heated under reflux conditions, when alcohol and water are removed, which are formed by azeotropic distillation. After the formation of water has ceased (approximately 8 hours), the resulting solution is cooled and the resulting solid is removed by filtration, heated with hexane and dried by air. you one 41.5 g (67%), mp 157-160 ° C. C, q Hjjj Ng. Monochlorohydrate. To a solution of 3.25 g of the above base in 20 ml of absolute ethanol, add 2 ml of 5N solution HCl in ethanol. The solution is diluted with an equal volume of ethyl acetate solid, which is separated, removed by filtration, and recrystallized from absolute alcohol. The yield is 3.1 g, m.p. 20b-20g C1. Dichlorohydrate. To a solution of 3.25 g of the above described base, dissolved in 20 ml of absolute ethanol, is added with 4 ml of 5N ethanol of hydrochloric acid. The solid which is separated is filtered and recrystallized from absolute ethanol. The yield is 3.2 g, m.p. 253-254 s. C c yrjti -2HC If the same hydrochloride is re-crystallized from alcohol, 3.0 g of product is obtained, mp. 214-215s. Cio N57 N5-2S1 - HgO Maleat. The solution obtained by dissolving 3.25 g of the above base nid in 20 ml of absolute ethanol is mixed with a solution of 1.16 g of maleic acid in 10 ml of absolute ethanol and diluted with 30 ml of ethyl acetate. The solid is collected by filtration and recrystallized from absolute alcohol. Output 2.5 g, so pl. 153154 C. С, с, Н.7 ,, Example 4. Preparation of {3-chlorophenyl) -1-piperazinyl-ethyl-5,6,7,8-tetrahydro-5-triazole (4,3-a) - pyridine (R 3-C1; R N). a) Hydrazide 4- (3-chlorophenyl) -piperazinyl propionic acid. A solution of 14 g (0.048 mol) of ethyl 4- (3-chlorophenyl) -piperazinyl-propionic acid and 12.5 g (0.25 mol) of hydrazine hydrate (99%) in 20 ml of ethanol is heated under reflux for 4 h. The solution was removed from the resulting solution under reduced pressure, the residue was separated with water and the oil, which was separated, extracted with chloroform. The residue that is obtained after removal of chloroform is recrystallized from hexane-ethyl acetate mixture. The yield is 13 g (98%), m.p. 110-112 ° C. C, H) C 1 H D O. b) A mixture of 2.5 g (0.022 mol) of 2-thio T1iperidone, 5.4 g (0.019 mol) of the above hydrazine and O, 1 g of dry sodium methoxide is heated with stirring at 120-130 ° C for 4 h After heating is complete, the residue is diluted in water. The solid thus obtained is filtered and, after air drying, is grown in absolute alcohol. An excess of an ethanolic hydrochloric acid solution is added to the solution and the solid that precipitates is collected by filtration and recrystallized from absolute ethanol. Yield 6 g (75%), so pl. 211 ° C. H, ii ClN5 2HCl Example 5. Preparation of 3-2-t4 (2-tolyl) -1-piperazinyl-ethyl-5.66, 8-tetrahydro-5-triazole (4,3-a) -pyridine (n 2; m 4; R 2-СНп; R - Н) a) 4- (2-Tolyl) -piperazinyl-propiones hydrazide O 3 acid with 3,4,5,6-tetrahydro-2-hydrazino-pyridine. To a solution of 8 g (0.07 mol) of o-methylvalerolactam in 120 ml of benzene was added 17.5 g (0.067 mol) of 4- (2-tolyl) piperazinyl propanoic acid hydrazide. The suspension is vigorously stirred for 3 hours at room temperature. The resulting solid is collected by filtration and washed with benzene. Yield 20 g (87%), so pl. with decomposition (preheated bath). H2) N50 b) 18 g (0.053 mol) of the above hydrazide are suspended in 200 ml of benzene. The mixture was heated under reflux for 3 hours, and the resulting water was removed azetropically. Upon completion of the heating, the mixture is cooled, the solid that is formed is removed by filtration and recrystallized from benzene. Yield 15 g (88%), so pl. 161-162 ° C. C-19 V7 6 Example 6. Compounds are prepared according to one of the methods described in examples 1-4. 3- (2,5-Dichlorophenyl) -1-piperazinyl-ethyl-6, 7,9-tetrahydro-5H-S-triazole (4,3-a) azepine (n 2; t 5; R 2-C1; R 5-C1). Monochlorine hydrate. m.p. 220Рс (from alcohol at 95 ° С). Hydrazide 4- (2,5-dichlorophenyl) -pipo-rasinil-propionic acid, necessary for the synthesis of the specified product, prepared by the previously described method / so pl. 135-137 ° C (and (tilacetate). With HieCijNifO 4- (2,5-dichlorf-NILE) ethyl ester, d / 1 synthesis of the specified tiderazide, is prepared using the described method, mp . 198-2000C (1 mm Hg). 15 (0. &C; liiNij Ori 3- 2.5-Dichlorophenyl) -2-piperazine3-ethyl -5,6,7, in-tetrahydro S-triazole- (4,3-a) pyridine (p - 2; 4; I 2-C1; I 5-C. Dichlorohydrate. HjO m.p., (from alcohol at 950 s). 3-2-C4- (3-Chlorophenyl) -1-piperaeiyl1-ethyl1g-6 7, 8,9-tetrahydro-5H-5-triazole (4,3-a) azepine {n 2; m 5; R - 3-C1; R Н).
    Chlorogilrath, mp, 234 ° C (from absolute ethanol).
    3- 3-C4- (2-Tolyl) -1-piperazinyl 3 -propyl-6, 7,8,9 tetrahydro-5H 5-triazole (4,3-a) azepine (n 3; m 5; R - R - H).
    Monochl hydrate, tpl, 271 ° C (from absolute ethanol).
    3-52-1 4- (2-Methoxyphenyl) -1-pipera zinil-ethyl-6,7,8,9-tetrahydro-5H-5 triazole (4,3-a) azepine (n 2; m 5; R 2-OCHn ;; R H).
    Monohydrochloride, so pl. (from absolute ethanol).
    Compounds; obtained by the proposed method with the introduction (prescription) in certain quantities are effective for treating the state of increased ocular pressure, including glaucoma, with local or systemic. the use of psychopathological sympats94OV of psychosis of the schizophrenic type, in particular, hallucinations and delusions, when administered orally or parenterally, abstinence syndromes in patients with states of psychophysical STOP or dependence on alcohol, smoking or pharmaceutical preparations, by oral or parenteral use,
    In the latter cases, the treatment in this way does not replace other forms of treatment currently used, but abstinence syndrome is eliminated by acting on the physiological mechanisms that cause it. Offered compounds, therefore, can Russ | Attract as adjunctive or additional agents that can be used in combination with other forms of therapy, such as psychopathis, to accelerate the elimination of the disease process.
    The therapeutic value of the proposed compounds for each of the described cases is determined by using experimental models to deactivate the effect on each of the various symptoms mentioned above. Ability to reduce ocular pressure It was studied on normal rabbits using already known experimental conditions G23 and Z}.
    An example of elevated ocular pressure used in the experiments is the pressure caused by the reintroduction of betamethasone suspension into one or both eyes of the rabbit. Thus, it is possible to obtain a stable elevated eye pressure, which cannot be distinguished from human glaucoma.
    Test products reduce the pressure in normal rabbits and in the kropik with increased eye pressure, both when applied topically in the form of eye drops at a concentration of 0.25-0.5%, and when used parenterally in doses between 0.11 mg / kg of live weight .
    In the treatment of increased eye pressure, the proposed compounds are compared with pilocarpine in the form of eye drops with a concentration of 0.5-1% and it turns out that they are equally active. However, the proposed compounds do not cause miosis and other irritations. In addition, they exhibit activity similar to that of neuroleptic substances in routine laboratory tests used to study this class of pharmaceutical preparations. Products are compared with chlorpromazine and show activity similar to that of the latter. Compared with the latter and other conventional antipsychotic agents, the compounds proposed have a lower toxicity and lack of catatonia, on the basis of which they can be regarded as free from extrapyrimidal type side effects, which, on the other hand, are a common characteristic of other antipsychotic agents. Finally, the experiments that led to the use of the proposed compounds for the treatment of addictions or habits of alcohol, smoking, and some pharmaceutical substances whose consumption is in the habit, were carried out using a completely new technique.
    It is known that the propensity or dependence on alcohol or other substances is considered to be the manifestation of the psychological adaptation that the body produces to compensate for the depressive effect of these agents. When the administration of the latter is stopped, adaptations exhibited by the body are no longer balanced by the opposite effects of these agents, and subsequently symptoms of a rejection reaction appear. As it is known, the rejection reaction itself is accompanied by actually symptoms of excessive excitability, muscle tension and cracking, agitation, insomnia and, in more serious cases, convulsion. For these experiments, the working theory is that on the basis of the tendency or dependence, and, consequently, abstinence syndrome, there is a general physiological mechanism that the organism uses to adapt to various agents, such as smoking, alcohol , narcotic painkillers, etc.
    To test this theory, the hivot develop a propensity syndrome.
    权利要求:
    Claims (1)
    [1]
    Claim
    A method for producing cycloalkyl triazoles of the general formula I of patients with a tendency or dependence of a different nature, while discovering a new method of action.
    In fact, they act on the physiological system that the body uses to counterbalance the depressant effects of substances such as alcohol and morphine. The proposed method can be used to combat the symptoms of abstinence using non-replacement therapy methods, which are often as dangerous as the agent that causes addiction (as in in the case of methadone used in the treatment of addiction to morphine or other drugs), but by directly acting on the physiological system that is responsible for the syndrome, where η = 2 or 3;
    m = 4 or 5, and each of R and R 1 is selected from the group consisting of hydrogen, methyl, chloro, or their salts, characterized in that the hydrazide arylpiperase and nylalkanoic acids of formula II
    - (CH ^ P- SONGOM, where R.R'h η have the above meanings, is heated with the compound of formula III and IV holding.
    Therapeutic treatments include oral administration of products and administration at an average dose of 25-50 mg three times a day. When leche- l SRI schizophrenia and other forms of psychosis, as well as in the treatment of abstinence syndrome is particularly serious, the dose used may reach 200 mg
    0A1K or subsequent isolation of the target product in the form of a base or salt.
    类似技术:
    公开号 | 公开日 | 专利标题
    SU852174A3|1981-07-30|Method of preparing cycloalkyltriazoles or theirs alts
    SU1544190A3|1990-02-15|Method of producing thiazolo/4,5-c/quinoline or its acid-additive salts
    DE69434380T2|2006-05-04|Pyridazino-quinoline compounds
    US4499091A|1985-02-12|1-Amino |-1,4-dihydro-4-oxo-6-fluoro-7-heterylquinoline-3-carboxylic acids and their use as antibacterial agents
    US2390555A|1945-12-11|Antispasmodic agents
    US3399201A|1968-08-27|Aminoalkyl-ethano-anthracenes
    CZ290325B6|2002-07-17|Alkoxyalkyl carbamates of imidazo[1,2-a]pyridines and pharmaceutical preparation in which the carbamates are comprised
    DD201903A5|1983-08-17|PROCESS FOR THE PREPARATION OF DERIVATIVES OF THIENOPYRIDONONE
    DE2362553A1|1974-06-20|NEW PIPERAZINE DERIVATIVES
    EP0090424B1|1986-05-28|New quinolone compounds and preparation thereof
    US4325952A|1982-04-20|Method of treating abstinence syndrome with cycloaklyltriazoles
    JPH0699307B2|1994-12-07|Anti-dementia agent
    SU1549482A3|1990-03-07|Method of producing ergoline derivative
    SU810080A3|1981-02-28|Method of preparing |dioxazocin derivatives or their acid-additive salts
    SU1364623A1|1988-01-07|5,10-dihydro-11h-dibenzo-|-diazepine-11-ons substituted in position 5 or their physiologically compatible salts with inorganic or organic acids showing antiulcerous and secretion-suppressing activity
    US2807617A|1957-09-24|Acylpiperazines and methods of preparing the same
    DE1695812C3|1980-10-16|Dibenzo [c, f] -1,2-thiazepine derivatives, process for their preparation and pharmaceutical preparation containing them
    US4868299A|1989-09-19|Antibacterially active pyrido-benzothiazine derivatives with long-term action
    US4307096A|1981-12-22|Method of treating glaucoma with cycloalkyltriazoles
    CZ695188A3|1993-07-14|ENOL ETHER OF 1,1-DIOXIDE OF 6-CHLORO-4-HYDROXY-2-METHYL-N- |-1,2-THIAZINECARBOXYLIC ACID AMIDE, PROCESS OF ITS PREPARATION AND ITS USE
    KR820001450B1|1982-08-16|Process for preparing cycloalkyl-triazoles
    DE2340217A1|1974-02-21|3-BENZOYLTHIOPHENE, THEIR SALT, METHOD OF MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
    JPH0662608B2|1994-08-17|Carbostyril derivative
    DE2030714A1|1971-02-04|New Tricychic Compounds and Processes for Their Preparation
    US2803627A|1957-08-20|Therapeutic quinoline compounds
    同族专利:
    公开号 | 公开日
    CH639847A5|1983-12-15|
    IL56926D0|1979-05-31|
    IE790646L|1979-10-18|
    GB2020269A|1979-11-14|
    NL186635B|1990-08-16|
    BG40654A3|1987-01-15|
    AU520788B2|1982-02-25|
    DK156779A|1979-10-19|
    DE2915318C2|1990-12-13|
    NL7902489A|1979-10-22|
    FR2423221B1|1983-03-18|
    IT1094076B|1985-07-26|
    DK148480B|1985-07-15|
    PL214969A1|1980-03-10|
    JPS5817757B2|1983-04-09|
    US4252721A|1981-02-24|
    DE2915318A1|1979-10-31|
    NL186635C|1991-01-16|
    AT374477B|1984-04-25|
    ATA292479A|1983-09-15|
    PT69502A|1979-05-01|
    IT7822421D0|1978-04-18|
    CA1104567A|1981-07-07|
    US4307095A|1981-12-22|
    SE437663B|1985-03-11|
    IE47965B1|1984-08-08|
    BG61367B2|1997-06-30|
    SE7903327L|1979-10-19|
    FR2423221A1|1979-11-16|
    YU86279A|1983-12-31|
    PL116103B1|1981-05-30|
    GB2020269B|1982-06-03|
    AU4583279A|1979-10-25|
    IL56926A|1983-09-30|
    YU41338B|1987-02-28|
    FI791217A|1979-10-19|
    JPS54157576A|1979-12-12|
    HU179917B|1983-01-28|
    DK148480C|1985-12-16|
    FI66378B|1984-06-29|
    FI66378C|1984-10-10|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2913454A|1956-11-23|1959-11-17|Schenley Ind Inc|Certain cycloalkanotriazoles, process and intermediates|
    IT1066857B|1965-12-15|1985-03-12|Acraf|DERIVATIVES OF S IPIAZOLE 4.3 A PYRIDIN AND PROCESSES FOR THEIR PREPARATION|
    US3472853A|1967-05-29|1969-10-14|Sterling Drug Inc|1--s-triazolyl)-lower-alkyl)-4-substituted- piperazines|
    JPS5070389A|1973-10-30|1975-06-11|CA1248531A|1984-04-17|1989-01-10|Jeffrey C. Watkins|4-substituted piperazine-2-carboxylic acids|
    FR2580648B1|1985-04-17|1987-05-15|Adir|NOVEL TRIAZOLE DERIVATIVES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|
    US4879294A|1988-01-28|1989-11-07|Angelini Pharmaceuticals Ltd.|Opthalmic composition|
    IT1224250B|1988-06-10|1990-09-26|Acraf|ASSOCIATION OF DEPIPRAZOLE WITH MORFINA|
    IT1250701B|1991-07-24|1995-04-21|Angelini Francesco Ist Ricerca|SOLID PHARMACEUTICAL COMPOSITION FOR ORAL USE BASED ON DAPIPRAZOLE|
    US5288759A|1992-08-27|1994-02-22|Alcon Laboratories, Inc.|Use of certain sulfamoyl-substituted phenethylamine derivatives to reverse drug-induced mydriasis|
    US6187774B1|1996-03-04|2001-02-13|Yoshitomi Pharmaceutical Industries, Ltd.|Fused heterocyclic compounds and pharmaceutical applications thereof|
    NZ510685A|1998-09-30|2003-10-31|Takeda Chemical Industries Ltd|Drugs for improving vesical excretory strength|
    IL141235A|2000-02-09|2012-04-30|Novartis Int Pharm Ltd|Combined use of an alpha-adrenoceptor antagonist and a muscarinic antagonist in the manufacture of a medicament for the treatment of benign prostatic hyperplasia|
    US6730691B1|2000-02-10|2004-05-04|Miles A. Galin|Uses of alpha adrenergic blocking agents|
    US20020065286A1|2000-08-21|2002-05-30|Davies Michael John|Treatment of wounds|
    US20020091129A1|2000-11-20|2002-07-11|Mitradev Boolell|Treatment of premature ejaculation|
    WO2003004058A1|2001-07-02|2003-01-16|Santen Pharmaceutical Co., Ltd.|OPTIC NERVE PROTECTING AGENTS CONTAINING α1 RECEPTOR BLOCKER AS THE ACTIVE INGREDIENT|
    GB0130219D0|2001-12-18|2002-02-06|Pfizer Ltd|Compounds for the treatment of sexual dysfunction|
    US20030229001A1|2002-01-31|2003-12-11|Pfizer Inc.|Treatment of male sexual dysfunction|
    DE60336485D1|2002-08-19|2011-05-05|Pfizer|COMBINATION THERAPY AGAINST HYPERPROLIFERATIVE DISEASES|
    GB0219961D0|2002-08-28|2002-10-02|Pfizer Ltd|Oxytocin inhibitors|
    US7323462B2|2002-12-10|2008-01-29|Pfizer Inc.|Morpholine dopamine agonists|
    CA2451267A1|2002-12-13|2004-06-13|Warner-Lambert Company Llc|Pharmaceutical uses for alpha2delta ligands|
    PA8597401A1|2003-03-14|2005-05-24|Pfizer|ACID DERIVATIVES 3-PROPILCARBAMOIL] CICLOALQUIL) PROPANOIC AS NEP INHIBITORS|
    US20040220186A1|2003-04-30|2004-11-04|Pfizer Inc.|PDE9 inhibitors for treating type 2 diabetes,metabolic syndrome, and cardiovascular disease|
    KR20060021870A|2003-05-30|2006-03-08|랜박시 래보러터리스 리미티드|Substituted pyrrole derivatives and their use as hmg-co inhibitors|
    US20050065158A1|2003-07-16|2005-03-24|Pfizer Inc.|Treatment of sexual dysfunction|
    US20050037063A1|2003-07-21|2005-02-17|Bolton Anthony E.|Combined therapies|
    US7291640B2|2003-09-22|2007-11-06|Pfizer Inc.|Substituted triazole derivatives as oxytocin antagonists|
    US20050267096A1|2004-05-26|2005-12-01|Pfizer Inc|New indazole and indolone derivatives and their use pharmaceuticals|
    US20050288270A1|2004-05-27|2005-12-29|Pfizer Inc|New aminopyridine derivatives and their use as pharmaceuticals|
    JP2008533193A|2005-03-21|2008-08-21|ファイザー・リミテッド|Substituted triazole derivatives as oxytocin antagonists|
    ES2313626T3|2005-03-21|2009-03-01|Pfizer Limited|TRIAZOL DERIVATIVES SUBSTITUTED AS AN OXITOCINE ANTAGONISTS.|
    CA2618103A1|2005-08-10|2007-02-15|Pfizer Limited|Substituted triazole derivatives as oxytocin antagonists|
    GT200600381A|2005-08-25|2007-03-28|ORGANIC COMPOUNDS|
    US7741317B2|2005-10-21|2010-06-22|Bristol-Myers Squibb Company|LXR modulators|
    EP1948599A1|2005-11-08|2008-07-30|Ranbaxy Laboratories Limited|Process for -7-[2--5-isopropyl-3-phenyl-4- [ carbonyl]-pyrrol-1-yl]-3, 5-dihydroxy-heptanoic acid hemi calcium salt|
    US7888376B2|2005-11-23|2011-02-15|Bristol-Myers Squibb Company|Heterocyclic CETP inhibitors|
    US8383660B2|2006-03-10|2013-02-26|Pfizer Inc.|Dibenzyl amine compounds and derivatives|
    US7919506B2|2006-03-10|2011-04-05|Pfizer Inc.|Dibenzyl amine compounds and derivatives|
    US20070238716A1|2006-03-14|2007-10-11|Murthy Ayanampudi S R|Statin stabilizing dosage formulations|
    TW200811101A|2006-07-14|2008-03-01|Ranbaxy Lab Ltd|Polymorphic forms of an HMG-CoA reductase inhibitor and uses thereof|
    WO2008070496A2|2006-12-01|2008-06-12|Bristol-Myers Squibb Company|N--2, 2--propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases|
    CA2909442A1|2013-04-17|2014-10-23|Pfizer Inc.|N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases|
    WO2016055901A1|2014-10-08|2016-04-14|Pfizer Inc.|Substituted amide compounds|
    EP3870170A1|2018-10-26|2021-09-01|Ocuphire Pharma, Inc.|Methods and compositions for treatment of presbyopia, mydriasis, and other ocular disorders|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    IT22421/78A|IT1094076B|1978-04-18|1978-04-18|CICLOALCHILTRIAZOLI|
    [返回顶部]