WO2001087881A1 - Piperidyindoles comme ligands du recepteur de la serotonine - Google Patents
Piperidyindoles comme ligands du recepteur de la serotonine Download PDFInfo
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- WO2001087881A1 WO2001087881A1 PCT/US2001/011744 US0111744W WO0187881A1 WO 2001087881 A1 WO2001087881 A1 WO 2001087881A1 US 0111744 W US0111744 W US 0111744W WO 0187881 A1 WO0187881 A1 WO 0187881A1
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- alkyl
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- 0 **(CC=C1CN*)CC=C1[N+]([O-])=O Chemical compound **(CC=C1CN*)CC=C1[N+]([O-])=O 0.000 description 1
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- C07—ORGANIC CHEMISTRY
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- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Definitions
- This invention relates to pharmaceutical compounds and their use in the treatment of disorders of the central nervous system.
- R 1 and R 2 are each hydrogen or C ⁇ __6 alkyl
- R 3 is -SR 10 , -SOR 10 , - S0 2 R 10 , -COR 10 , -CH 2 OH or
- R 10 is C]__g alkyl and R 11 is hydrogen or
- R 4 , R 5 , R 6 and R 7 are each hydrogen or ⁇ - Q alkyl
- R 4 , R 5 , R 6 and R 7 is C ⁇ - ⁇ alkyl ,
- R and R ⁇ are each hydrogen, halo, C ] __g alkyl or cyano,
- n 0 or 1 and m is 2 or 3,
- Y is wherein R 12 and R 13 are each hydrogen, C]__g alkyl, cyclopropyl or cyclopropyl-C ⁇ _g alkyl ;
- the compounds of the invention and their pharmaceutically acceptable salts are indicated for use in the treatment of disorders of the central nervous system.
- the present invention also provides the ue of a compound of the present invention in the preparation of a medicament for the treatment of a disorder of the central nervous system.
- a halo atom is preferably chloro, bromo or fluoro, and is especially fluoro.
- C ] __ alkyl group can be methyl, ethyl, propyl , butyl or
- pentyl or hexyl and can be branched or unbranched including isopropyl and tert . butyl.
- Preferred compounds are those which have one or more of the following features:
- R 8 and R 9 are each hydrogen or halo
- R 8 and 9 are each hydrogen or fluoro
- R 8 is fluoro and R 9 is hydroge ;
- R 8 is fluoro in the 6-position, and R 9 is hydrogen
- Y is C wherein R 12 and R 13 are both C, , alkyl ;
- n 1 and R 1 and R 2 are both hydrogen;
- R 3 is at the 6-position or the 7-position, preferably at the 6-position
- R 3 is -SOR 10 , -S0 2 R 10 or -COR 10 ;
- R 0 is methyl or ethyl, and especially methyl
- R 3 is -SOCH3 or -SO2CH3, at the 6-position or
- the 7-position preferably at the 6-position
- R 4 is C ⁇ _g alkyl.
- a preferred group of compounds is of the following formula:
- R 8 and R ⁇ are each hydrogen or halo, preferably fluoro
- R 3 is at the 6- or 7- position and is -SOR 10 , -S0 2 R 10 or
- R 4 is C ⁇ - Q alkyl
- R 12 is C ⁇ _ alkyl; and salts thereof.
- a further preferred group of compounds is of the following formula
- R 8 and R9 are each hydrogen or halo, preferably fluoro
- R 3 is in the 6- or 7-position and is -SOR 10 , -S0 2 R 10 or
- R 4 is C ⁇ _g alkyl
- R 12 and R 13 are each hydrogen or C _g alkyl; and salts
- a further preferred group of compounds is of the following formula:
- R 8 and R 9 are each hydrogen or halo, preferably fluoro
- R 3 is in the 6- or 7-position and is -SOR 10 , -S0 2 R 10 or
- R 4 is _ ⁇ alkyl
- R 12 and R 13 are each hydrogen or C]__g alkyl; and salts
- a further preferred group of compounds is of the following formula:
- R 8 and R9 are each hydrogen or halo, preferably fluoro
- R 3 is in the 6- or 7-position and is -SOR 10 , -S0 2 R 10 or
- R 4 is C ⁇ _g alkyl
- R 12 and R 13 are each hydrogen or C ] __g alkyl; and salts
- Acid addition salts are preferably the pharmaceutically acceptable, non-toxic addition salts with suitable acids, such as those with inorganic acids, for example hydrochloric, hydrobromic, nitric, sulphuric or phosphoric acids, or with organic acids, such as organic carboxylic acids, for example, pyruvic, lactobionic, glycollic, maleic, hydroxymaleic, fumaric, malic, tartaric, citric, salicyclic, o-acetoxybenzoic, or organic sulphonic, 2 -hydroxyethane sulphonic, toluene-p-sulphonic, naphthalene-2-sulphonic, bisethanesulphonic acid or methanesulphonic acid.
- suitable acids such as those with inorganic acids, for example hydrochloric, hydrobromic, nitric, sulphuric or phosphoric acids
- organic acids such as organic carboxylic acids, for example, pyruvic, lactobionic, glycollic, male
- salts are included in the invention. They may serve as intermediates in the purification of compounds or in the preparation of other, for example pharmaceutically acceptable, acid addition salts, or are useful for identification, characterisation or purification.
- Some of the compounds of the invention contain one or more asymmetric carbon atoms which gives rise to isomers. Moreover, compounds which are substituted by a
- sulphinyl group (R 3 is -SOR 10 ) also exist in isomeric forms. These compounds are normally prepared as racemic mixtures and can conveniently be used as such, but individual isomers can be isolated by conventional techniques, if so desired. Such racemic mixtures and individual optical isomers form part of the present invention. It is preferred to use an enantiomerically pure form.
- the invention also includes a process for producing a compound of formula (I) above, which comprises reacting a compound of the formula:
- n and m, and the substituents have the values given above, and (i) Z is -CH 2 W, where W is a leaving
- reaction is preferably carried out in a polar solvent such as, for example, acetonitrile or water, at a temperature of from 50°C. to 150°C, and in the presence of sodium iodide and a base such as, for example, sodium carbonate.
- a polar solvent such as, for example, acetonitrile or water
- sodium iodide and a base such as, for example, sodium carbonate.
- the reaction is one of reductive amination using, for example, sodium cyanoborohydride , borane in pyridine or triacetoxy borohydride in the presence of the compound of formula (III) .
- the intermediate compounds of formula (III) can be made by reacting an indole with the appropriate piperidinone .
- V is halo, preferably bromo, with a compound of formula :
- Preferred ethane derivatives of formula (V) are dihalo- ethanes, for instance bromo chloroethane, and the reaction is preferably carried out in an organic solvent such as, for example, dimethyl formamide, with a strong base such as sodium hydride, at a temperature of from 0 C. to 100 C, for instance room temperature.
- Aldehyde intermediates of formula (IV) can be prepared from the appropriate alkene by oxidation employing, for example, ozone or osmium tetroxide .
- compounds of formula (VI) can be prepared by a synthetic route, such as the following:
- the principal route of synthesis is by means of a reaction between the appropriate sulfamoyl compound prepared from an aniline and sulfamoyl chloride and trioxan, in the presence of an acid, for example, an alkyl sulfonic acid:
- compounds of formula (VII) can be synthesised by reaction of sulfamide with an amino benzylamine in pyridine or diglyme .
- the amino benzylamine can be prepared in three steps from the appropriate nitrobenzoic acid via amide formation and a two step reduction as, for example:
- N-sulfamoyloxazolidinone is then reacted with an aniline of formula
- formula (VII) can be prepared by oxidation of the -SR 10 substituted compound, by the use of metachloro perbenzoic acid or Oxone® or sodium perborate or osmium tetroxide/sodium periodate .
- the compounds of the invention and their pharmaceutically acceptable salts have useful central nervous system activity. They have been shown to increase release of tritiated-5HT from guinea pig cortical slices in a test with the following procedure.
- the slices were washed in basal buffer containing 1 ⁇ M paroxetine and then transferred to baskets.
- the baskets were used to transfer the tissue between the washing and release buffers, all of which contained 1 ⁇ M paroxetine.
- the slices were incubated for 11 minutes in buffer and then transferred for 4 minutes to a second tube containing buffer. Following incubation they were again transferred, for a further 4 minutes, to a buffer in which NaCl had been substituted, on an equimolar basis, to give a KCl concentration of 30 mM (release sample) .
- the tritium in the tissue samples and in the buffers from the three incubation periods was estimated by liquid scintillation spectroscopy. Test compound was present throughout the three incubation periods.
- the compounds of the invention enhanced release of 5-HT.
- the compounds of the present invention are indicated for use in treating a variety of conditions such as depression, obesity, bulimia, alcoholism, pain, hypertension, ageing, memory loss, sexual dysfunction, anxiety, schizophrenia, gastrointestinal disorders, headache, cardiovascular disorders, smoking cessation, drug addiction, emesis, epilepsy, Alzheimer's and sleep disorders.
- Compounds of the present invention may be particularly useful in the treatment of depression.
- Compounds of the invention may also be useful for the treatment of obsessive compulsive disorder.
- the present invention also provides a method of treating a warm blooded mammal including a human suffering from or susceptible to a disorder of the central nervous system, which comprises administering to said human an effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof.
- the present invention further provides a method of inhibiting the 5-HT2A receptor which comprises administering to a warm blooded mammal including a human in need of such treatment a therapeutically effective amount of a 5-HT2A antagonist of formula I.
- the present invention also provides a method of inhibiting the reuptake of serotonin, which comprises administering to a warm blooded mammal including a human in need of such treatment a therapeutically effective amount of a serotonin reuptake inhibitor of formula I .
- the compounds of the invention are effective over a wide dosage range, the actual dose administered being dependent on such factors as the particular compound being used, the condition being treated and the type and size of mammal being treated.
- the dosage required will normally fall within the range of 0.01 to 20 mg/kg per day, for example in the treatment of adult humans, dosages of from 0.1 to 100 mg per day may be used, preferably from 2 to 20 mg per day as, for example, for the preferred compounds of formula (II) and (III) .
- compositions are prepared in a manner well known in the pharmaceutical art and comprise at least one active compound .
- the invention includes a pharmaceutical composition
- a pharmaceutical composition comprising as active ingredient a compound of formula (I) or a pharmaceutically acceptable salt or ester thereof, associated with a pharmaceutically acceptable excipient .
- the active ingredient will usually be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier which may be in the form of a capsule, sachet, paper or other container.
- the excipient may be a solid, semi-solid or liquid material which acts as a vehicle, excipient or medium for the active ingredient.
- compositions of the invention may, if desired, be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient.
- the foregoing compositions may be formulated as tablets, capsules or suspensions for oral use and injection solutions or suspensions for parenteral use or as suppositories.
- compositions are formulated in a dosage unit form, each dosage containing from 0.1 to 100 mg, more usually 2 to 20 mg, of the active ingredient.
- 6-Fluoro-3- (6 -methyl-1, 2.3, 6-tetrahydro-4- pyridinyl) -lH-indole and 6-fluoro-3- (2-methyl- 1,2, 3, 6-tetrahydro-4-pyridinyl) -lH-indole
- Powdered potassium hydroxide (4.01 g, 71.5 mmol) is dissolved in a mixture of methanol (70 ml) and water (1 ml) , and stirred until no solid remains.
- 6-Fluoro indole (1.10g, 8.73 mmol)
- 2- methylpiperidone trifluoroacetic acid salt (4.18g, 18.4 mol)
- 2-methyl 4-piperidones can be synthesised by known methods in the literature , for example Mistryukov, E. A.; Aronova, N. I. Izv. Akad. Nauk SSSR, Ser. Khim. (1966), (12), 2171-6.
- Di-tert butyl dicarbonate (5.90g, 0.027 mol) is dissolved in THF at 0°C, and a mixture 6-fluoro-3- (6- methyl-1, 2 , 3 , 6-tetrahydro-4-pyridinyl) -lH-indole and 6- fluoro-3- (2-methyl-l, 2,3, 6-tetrahydro-4-pyridinyl) -1H- indole (5.17g, 0.022 mol) is added portionwise over 5 minutes. The mixture is stirred at this temperature for 1 hour, then for 3 hours at room temperature, before 100 ml aqueous sodium bicarbonate (sat. solution) is added.
- N- (4-Methylthiophenyl) -N' - (1-methylethyl) sulfamide (4.35 g, 0.016 mol) was dissolved in dry dichloromethane (150 ml) and methanesulphonic acid (18.87 ml, 0.303 mol) . The solution was cooled at 0°C. before the addition of trioxan (0.480 g, 0.005 mol) in dichloromethane (15 ml) . After stirring at 0°C.
- Phosphorus pentoxide (4.49 g, 0.032 mol) was added to a stirred solution of N- (4-methylthiophenyl) - 2, 2-dimethylmalonamic acid (5.0 g, 0.020 mol) in methanesulfonic acid (35 ml) .
- the reaction mixture was warmed to 70°C. and stirred for 90 mins .
- the product mixture was then cooled to room temperature and poured over ice.
- the product was extracted with ethyl acetate (2 x 200 ml) .
- Triethylsilane 34.75 ml, 49.1 g, 0.042 mol was added dropwise to a stirred solution of 3,3- dimethyl-6-methylthio-2,4 (1H,3H) -quinolinedione (12.79 g, 0.054 mol) in trifluoroacetic acid (520 ml) under nitrogen at 60°C.
- the reaction was then allowed to cool slowly to room temperature and was stirred for 16 hr.
- the solvent was then evaporated in vacuo to afford a yellow residue.
- the residue was then poured into saturated potassium carbonate solution (200 ml) .
- the product was extracted with ethyl acetate (3 x 150 ml) .
- Methyl 4-methylthio-2-nitro benzoate (10.4g; 0.046mol) was dissolved in ethanol and Raney nickel added as an aqueous suspension. The solution was hydrogenated at 60psi on a Parr hydrogenator for 6 hrs . The catalyst was filtered off through celite, washed with ethanol to give the product which was used directly in the next step. ( 8.9g; 98%)
- a racemic mixture of 6-fluoro-3- [ (2S, 4R) -2 - methylpiperidin-4-yl] -IH-indole and 6-fluoro-3- [ (2R, 4S) - 2 -methylpiperidin-4 -yl] -IH-indole (0.34g, 1.46 mmol), 1- (2-chloroethyl) -3-isopropyl-6- (methylsulfonyl) -3,4- dihydro-lff-2, 1, 3-benzothiadiazine 2,2-dioxide (0.64g, 1.74 mmol), sodium iodide (0.26g, 1.75 mmol) and sodium carbonate (0.90g, 8.49 mmol) are suspended in a mixture of water (50 ml) and acetonitrile (5 ml) , and stirred at reflux under nitrogen for 72 hours.
- EXAMPLE 2 Tablets each containing 10 mg of active ingredient are made up as follows:
- Microcrystalline cellulose 100 mg Polyvinylpyrrolidone (as 10% solution in water) 13 mg
- the active ingredient, starch and cellulose are mixed thoroughly.
- the solution of polyvinylpyrrolidone is mixed with the resultant powders and passed through a sieve.
- the granules so produced are dried and re-passed through a sieve.
- the sodium carboxymethyl starch and magnesium stearate are then added to the granules which, after mixing, are compressed on a tablet machine to yield tablets each weighing 300 mg.
- Capsules each containing 20 mg of active ingredient are made as follows : Active ingredient 20 mg
- the active ingredient, starch and magnesium stearate are passed through a sieve and filled into hard gelatine capsules in 200 mg quantities.
- Capsules each containing 20 mg of medicament are made as follows :
- Tablets each containing 20 mg and medicaments are made as follows:
- the active ingredient, lactose, microcrystalline cellulose, sodium starch glycollate and hydroxypropylmethylcellulose are passed through a sieve and blended together. Water is added to the blended powders to form a damp mass. The damp mass is passed through a coarse screen, dried, then re-screened. The dried granules are mixed with the magnesium stearate and compressed into tablets of 300 mg weight.
Abstract
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002410091A CA2410091A1 (fr) | 2000-05-18 | 2001-05-04 | Piperidyindoles comme ligands du recepteur de la serotonine |
JP2001584275A JP2003533523A (ja) | 2000-05-18 | 2001-05-04 | セロトニンレセプターリガンドとしてのピペリジルインドール群 |
AU2001259051A AU2001259051A1 (en) | 2000-05-18 | 2001-05-04 | Piperidyindoles as serotonin receptor ligands |
US10/258,356 US6844338B2 (en) | 2000-05-18 | 2001-05-04 | Piperidyindoles as serotonin receptor ligands |
EP01932534A EP1286992A1 (fr) | 2000-05-18 | 2001-05-04 | Piperidyindoles comme ligands du recepteur de la serotonine |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0012082A GB2362381A (en) | 2000-05-18 | 2000-05-18 | Pharmaceutically active indolyl-piperidines |
GB0012082.4 | 2000-05-18 |
Publications (1)
Publication Number | Publication Date |
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WO2001087881A1 true WO2001087881A1 (fr) | 2001-11-22 |
Family
ID=9891893
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2001/011744 WO2001087881A1 (fr) | 2000-05-18 | 2001-05-04 | Piperidyindoles comme ligands du recepteur de la serotonine |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1286992A1 (fr) |
JP (1) | JP2003533523A (fr) |
AU (1) | AU2001259051A1 (fr) |
CA (1) | CA2410091A1 (fr) |
GB (1) | GB2362381A (fr) |
WO (1) | WO2001087881A1 (fr) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1468996A1 (fr) * | 2000-06-14 | 2004-10-20 | H. Lundbeck A/S | Derivés d'indole pour le traitement des maladies du système nerveux central |
WO2008073956A2 (fr) * | 2006-12-12 | 2008-06-19 | Wyeth | Dérivés de sulfonamides cycliques et procédés relatifs à leur utilisation |
CN101250154B (zh) * | 2008-03-13 | 2011-05-04 | 台州市知青化工有限公司 | 一种工业化生产6-氟吲哚的方法 |
WO2018007323A1 (fr) * | 2016-07-04 | 2018-01-11 | Bayer Cropscience Aktiengesellschaft | Benzosultames et analogues et leur utilisation comme des fongicides |
CN112457235A (zh) * | 2020-12-02 | 2021-03-09 | 烟台凯博医药科技有限公司 | 一种7-甲基吲哚的制备方法 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR028685A1 (es) * | 2000-06-14 | 2003-05-21 | Lundbeck & Co As H | Derivados de indol |
TWI391387B (zh) * | 2004-05-12 | 2013-04-01 | Eisai R&D Man Co Ltd | 具有哌啶環之吲哚衍生物 |
AU2006244914A1 (en) * | 2005-05-11 | 2006-11-16 | Eisai R & D Management Co., Ltd. | Crystal of indole derivative having piperidine ring and process for production thereof |
AU2006244916B2 (en) * | 2005-05-11 | 2011-04-07 | Eisai R & D Management Co., Ltd. | Method for producing indole derivative having piperidine ring |
JP4932717B2 (ja) * | 2005-05-11 | 2012-05-16 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピペリジン環を有するインドール誘導体の製造方法 |
WO2008073958A2 (fr) | 2006-12-12 | 2008-06-19 | Wyeth | Dérivés de benzothiadiazinedioxyde substitués et procédés d'utilisation de ceux-ci |
Citations (11)
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EP0013612A2 (fr) * | 1979-01-08 | 1980-07-23 | Janssen Pharmaceutica N.V. | Dérivés de (pipéridinylalcoyl)quinazoline, procédé pour leur préparation et compositions pharmaceutiques les contenant |
FR2621588A1 (fr) * | 1987-10-08 | 1989-04-14 | Roussel Uclaf | Nouveaux derives de la 1,1-dioxo 1,2-benzoisothiazol 3-one, leur procede de preparation et leur application comme medicaments |
EP0350403A1 (fr) * | 1988-07-07 | 1990-01-10 | Rhone-Poulenc Sante | Dérivés de (aza)naphtalènesultame, leurs procédés de préparation et les médicaments les contenant |
FR2675801A1 (fr) * | 1991-04-24 | 1992-10-30 | Rhone Poulenc Rorer Sa | Piperidines, leur preparation et les medicaments les contenant. |
EP0536419A1 (fr) * | 1991-04-23 | 1993-04-14 | Toray Industries, Inc. | Derive de triazole tricyclique, production et utilisation de ce derive |
DE19500689A1 (de) * | 1995-01-12 | 1996-07-18 | Merck Patent Gmbh | Indolpiperidin-Derivate |
EP0897921A1 (fr) * | 1997-08-22 | 1999-02-24 | Eli Lilly And Company Limited | Dérivés de benzothiadiazinyl-indole et leur utilisation comme ligands des récepteurs de la sérotonine |
WO1999058525A1 (fr) * | 1998-05-13 | 1999-11-18 | Eli Lilly And Company Limited | Derives d'indole agissant comme des ligands de 5-ht2a et comme des inhibiteurs de reabsorption de la serotonine |
WO2000031074A2 (fr) * | 1998-11-19 | 2000-06-02 | Eli Lilly And Company Limited | Derives d'indole utilises comme ligands du recepteur de la serotonine |
WO2000049017A1 (fr) * | 1999-02-18 | 2000-08-24 | Eli Lilly And Company Limited | Dioxydes de 1-((indoly azacycloalkyl) alkyl)-2,1, 3-benzothiadiazole 2,2 faisant montre d'une activite de recepteur 5-ht2a |
WO2000078716A1 (fr) * | 1999-06-24 | 2000-12-28 | Toray Industries, Inc. | ANTAGONISTES DU RECEPTEUR ADRENERGIQUE-α¿1B? |
-
2000
- 2000-05-18 GB GB0012082A patent/GB2362381A/en not_active Withdrawn
-
2001
- 2001-05-04 AU AU2001259051A patent/AU2001259051A1/en not_active Abandoned
- 2001-05-04 CA CA002410091A patent/CA2410091A1/fr not_active Abandoned
- 2001-05-04 WO PCT/US2001/011744 patent/WO2001087881A1/fr not_active Application Discontinuation
- 2001-05-04 JP JP2001584275A patent/JP2003533523A/ja not_active Withdrawn
- 2001-05-04 EP EP01932534A patent/EP1286992A1/fr not_active Withdrawn
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
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EP0013612A2 (fr) * | 1979-01-08 | 1980-07-23 | Janssen Pharmaceutica N.V. | Dérivés de (pipéridinylalcoyl)quinazoline, procédé pour leur préparation et compositions pharmaceutiques les contenant |
FR2621588A1 (fr) * | 1987-10-08 | 1989-04-14 | Roussel Uclaf | Nouveaux derives de la 1,1-dioxo 1,2-benzoisothiazol 3-one, leur procede de preparation et leur application comme medicaments |
EP0350403A1 (fr) * | 1988-07-07 | 1990-01-10 | Rhone-Poulenc Sante | Dérivés de (aza)naphtalènesultame, leurs procédés de préparation et les médicaments les contenant |
EP0536419A1 (fr) * | 1991-04-23 | 1993-04-14 | Toray Industries, Inc. | Derive de triazole tricyclique, production et utilisation de ce derive |
FR2675801A1 (fr) * | 1991-04-24 | 1992-10-30 | Rhone Poulenc Rorer Sa | Piperidines, leur preparation et les medicaments les contenant. |
DE19500689A1 (de) * | 1995-01-12 | 1996-07-18 | Merck Patent Gmbh | Indolpiperidin-Derivate |
EP0897921A1 (fr) * | 1997-08-22 | 1999-02-24 | Eli Lilly And Company Limited | Dérivés de benzothiadiazinyl-indole et leur utilisation comme ligands des récepteurs de la sérotonine |
WO1999058525A1 (fr) * | 1998-05-13 | 1999-11-18 | Eli Lilly And Company Limited | Derives d'indole agissant comme des ligands de 5-ht2a et comme des inhibiteurs de reabsorption de la serotonine |
WO2000031074A2 (fr) * | 1998-11-19 | 2000-06-02 | Eli Lilly And Company Limited | Derives d'indole utilises comme ligands du recepteur de la serotonine |
WO2000049017A1 (fr) * | 1999-02-18 | 2000-08-24 | Eli Lilly And Company Limited | Dioxydes de 1-((indoly azacycloalkyl) alkyl)-2,1, 3-benzothiadiazole 2,2 faisant montre d'une activite de recepteur 5-ht2a |
WO2000078716A1 (fr) * | 1999-06-24 | 2000-12-28 | Toray Industries, Inc. | ANTAGONISTES DU RECEPTEUR ADRENERGIQUE-α¿1B? |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1468996A1 (fr) * | 2000-06-14 | 2004-10-20 | H. Lundbeck A/S | Derivés d'indole pour le traitement des maladies du système nerveux central |
WO2008073956A2 (fr) * | 2006-12-12 | 2008-06-19 | Wyeth | Dérivés de sulfonamides cycliques et procédés relatifs à leur utilisation |
WO2008073956A3 (fr) * | 2006-12-12 | 2008-07-24 | Wyeth Corp | Dérivés de sulfonamides cycliques et procédés relatifs à leur utilisation |
CN101250154B (zh) * | 2008-03-13 | 2011-05-04 | 台州市知青化工有限公司 | 一种工业化生产6-氟吲哚的方法 |
WO2018007323A1 (fr) * | 2016-07-04 | 2018-01-11 | Bayer Cropscience Aktiengesellschaft | Benzosultames et analogues et leur utilisation comme des fongicides |
US10736321B2 (en) | 2016-07-04 | 2020-08-11 | Bayer Cropscience Aktiengesellschaft | Benzosultams and analogues and their use as fungicides |
US11219214B2 (en) | 2016-07-04 | 2022-01-11 | Bayer Cropscience Aktiengesellschaft | Benzosultams and analogues and their use as fungicides |
CN112457235A (zh) * | 2020-12-02 | 2021-03-09 | 烟台凯博医药科技有限公司 | 一种7-甲基吲哚的制备方法 |
CN112457235B (zh) * | 2020-12-02 | 2023-04-25 | 烟台凯博医药科技有限公司 | 一种7-甲基吲哚的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
EP1286992A1 (fr) | 2003-03-05 |
JP2003533523A (ja) | 2003-11-11 |
GB0012082D0 (en) | 2000-07-12 |
CA2410091A1 (fr) | 2001-11-22 |
GB2362381A (en) | 2001-11-21 |
AU2001259051A1 (en) | 2001-11-26 |
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