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WO1993016048A1 - Compose d'acetamide substitue - Google Patents

Compose d'acetamide substitue Download PDF

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Publication number
WO1993016048A1
WO1993016048A1 PCT/JP1993/000142 JP9300142W WO9316048A1 WO 1993016048 A1 WO1993016048 A1 WO 1993016048A1 JP 9300142 W JP9300142 W JP 9300142W WO 9316048 A1 WO9316048 A1 WO 9316048A1
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WO
WIPO (PCT)
Prior art keywords
group
methyl
mixture
hydroxy
ethyl
Prior art date
Application number
PCT/JP1993/000142
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English (en)
Japanese (ja)
Inventor
Youichi Shiokawa
Kiyoshi Taniguchi
Kazuhiko Take
Kazunori Tsubaki
Hiroaki Mizuno
Original Assignee
Fujisawa Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fujisawa Pharmaceutical Co., Ltd. filed Critical Fujisawa Pharmaceutical Co., Ltd.
Publication of WO1993016048A1 publication Critical patent/WO1993016048A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

Definitions

  • the present invention relates to a novel substituted acetate amide compound and a pharmaceutically acceptable salt thereof, which has anticholinergic activity, in particular, nervous frequency, neurogenic bladder, nocturnal enuresis, unstable bladder, bladder spasm , Treatment for urinary frequency in diseases such as chronic cystitis and chronic prostatitis, urination disorder such as urinary incontinence; gastric ulcer, duodenal ulcer, hyperacidity, esophageal spasm, gastritis, enteritis, irritable bowel disease, intestine Colic, gallbladder, inflammation, cholangitis, pyloric spasm, pain associated with knee inflammation, ⁇ inflammation, biliary dyskinesia, sequelae after gallbladder resection, urolithiasis, cystitis, dysmenorrhea, hyperhidrosis, urinary tract Novel substituted acetate amide compounds and pharmaceutically acceptable compounds that are useful for treating convulsions such as convulsions and
  • An object of the present invention is to provide a novel substituted amide compound and a pharmaceutically acceptable salt thereof, which are useful for treating the above-mentioned diseases.
  • Another object of the present invention is to provide a formulation useful as a therapeutic agent for the above-mentioned diseases, which contains the substituted acetate amide compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the substituted acetate amide compound which is the object compound of the present invention is novel and is represented by the following formula (I).
  • R 1 and R 2 represent an aryl group which may have a suitable substituent
  • R 3 is hydrogen, hydroxyl or a lower alkyl group
  • R 4 is the formula (i):
  • R 5 represents hydrogen, methyl, ethyl, propyl, isopropyl or imino protecting group
  • R 6 represents a lower alkyl group
  • R 7 represents hydrogen, a lower alkyl group or an imino protecting group
  • a 1 and A 2 are lower alkylene groups
  • n and n each represent 0 or 1, respectively.
  • R 1 and R 2 are phenyl groups, R 3 is a hydroxyl group, A 2 is a methylene group, m is 0, and n force s 1, R 5 is ethyl Not a group,
  • the target compound (I) may have an asymmetric carbon atom, and stereoisomers in such a case are also included in the technical scope of the present invention.
  • a compound produced according to a method described in the below-mentioned Production Examples may be used as a starting material, and a compound produced according to a method described in the following Examples also may be used.
  • Suitable salts of the target compound (I) are conventional non-toxic salts, for example, formate, acetate, trifluoroacetate, maleate, tartaric acid
  • Organic salts such as salts, methanesulfonate, benzenesulfonate, and toluenesulfonate, for example, inorganic salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, and phosphate
  • Acid addition salts such as acid salts, or salts with amino acids such as arginine, aspartic acid and glutamic acid, or alkali metal salts such as sodium salts and calcium salts and calcium salts
  • Metal salts such as alkaline earth metal salts such as magnesium salts, ammonium salts, such as trimethylamine salts, triethylamino salts, pyridine salts, picolin salts, dicyclohexylamine salts, Organic base salts such as N—
  • “Lower”, unless otherwise indicated, means 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms.
  • Suitable examples of the "aryl group” in the “aryl group optionally having substituent (s)" include a phenyl group, a naphthyl group, a pentalenyl group, an anthracenyl group, and the like. Of these, a phenyl group is particularly preferred.
  • suitable substituents that can be substituted by the above “aryl group” include, for example, halogen (eg, fluorine, chlorine, bromine, iodine), lower alkyl group (eg, methyl, ethyl, propyl, Isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), lower alkoxy groups (eg, methoxy, ethoxy, propoxy, isopropoxy, butoxy, "b-butoxy, pentyloxy, hexyloxy, etc.)
  • halogen eg, fluorine, chlorine, bromine, iodine
  • lower alkyl group eg, methyl, ethyl, propyl, Isopropyl, butyl, t-butyl, pentyl, hexyl, etc.
  • lower alkoxy groups eg, methoxy, ethoxy, propoxy, isopropoxy
  • aryl group optionally having a substituent is a group having one suitable substituent selected from the group consisting of a halogen, a lower alkyl group and a lower alkoxy group. More preferred examples include a phenyl group having a halogen, a phenyl group having a -C 4) alkyl group, and a phenyl group having a (C, 1C 4) alkoxy group. Examples thereof include a phenyl group having chlorine, a phenyl group having fluorine, a phenyl group having methyl, and a phenyl group having methoxy.
  • lower alkyl include straight and branched ones such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl. etc. can be mentioned, et al are group, is a preferred example among them, (C, - c 4) alkyl group, and is a further preferred embodiment, a methyl group, Echiru group, blanking opening propyl group, Isopropyl, butyl and t-butyl groups.
  • Suitable examples of "imino protecting groups” include conventional protecting groups, i.e., substituted or unsubstituted trityl, benzhydryl, benzyl, 4-methoxybenzyl, etc.
  • An alkenyl (lower) alkyl group, a dinitropropyl group for example, a lower alkoxycarbonyl (lower) alkenyl group such as 1-methoxycarbonyl-1-propene-2-yl, for example, 1-benzoyl1-1-propene-1 2—Aroyl (lower) alkenyl group such as yl, for example, 2—Hydroxy such as hydroxybenzylidene
  • Examples thereof include a xyl (lower) alkylidene group, for example, a silyl compound such as tri (lower) alkylsilyl such as trimethylsilyl, and the following acyl group.
  • acyl group examples include an aliphatic acyl group, an aromatic acyl group, a heterocyclic acyl group, and an aliphatic acyl group substituted with an aromatic group or a heterocyclic group.
  • aliphatic acetyl group examples include a carbamoyl group, for example, a lower alkanoyl group such as formyl, acetyl, propionyl, butyryl, isobutyryl, norrelyl, isonoleryl, bivaloyl, and hexanoyl; for example, mesyl and ethanesulfonyl.
  • a carbamoyl group for example, a lower alkanoyl group such as formyl, acetyl, propionyl, butyryl, isobutyryl, norrelyl, isonoleryl, bivaloyl, and hexanoyl; for example, mesyl and ethanesulfonyl.
  • lower alkoxysulfonyl groups such as propanesulfonyl and the like, for example, lower alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, and tert-butoxycarbonyl, for example, acrylyl, and methanol
  • Lower alkenoyl groups such as lyroyl and crotonyl, for example, (C 3 -C 7) cycloalkanols such as cyclohexanecarbonyl, and the like, amidino groups such as methoxalyl, ethoxyl, and tertiary butoxy Alcoxari, such as A saturated or unsaturated acyclic or cyclic acyl group, such as a protected force such as a propyloxycarbonyl group.
  • aromatic acyl group examples include an aroyl group such as benzoyl, toluene, and xyloyl, and an arylene sulfonyl group such as benzenesulfonyl and tosyl.
  • heterocyclic acyl group examples include furyl, tenoyl, nicotinoyl, isonicotinoyl, thiazolylcarbonyl, thiadiazolylcarbonyl, tetrazolylcarbonyl, morpholinocarbonyl, and the like.
  • Examples of the aliphatic acetyl group substituted with an aromatic group include an alkenyl group such as a phenyl (lower) alkanol group such as phenyl acetyl, phenylpropionyl, and phenylhexanoyl.
  • Alkoxycarbonyl groups such as phenyl (lower) alkoxycarbonyl groups such as benzyloxycarbonyl and phenyloxycarbonyl, and phenoxy (such as phenoxyacetyl and phenoxypropionyl) Lower) alkanoyl groups and the like.
  • Aliphatic acryl groups substituted with a heterocyclic group include chenyl acetyl, imidazolyl acetyl, furyl acetyl, tetrazolyl acetyl, thiazolyl acetyl, thiadia azolyl acetyl, chenyl propionyl, and thiadiazolyl. And propionyl.
  • acyl groups are further substituted with lower alkyl groups such as carboxy groups such as methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, pentyl, and hexyl, such as chlorine, bromine, iodine and fluorine.
  • Lower alkyl groups such as carboxy groups such as methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, pentyl, and hexyl, such as chlorine, bromine, iodine and fluorine.
  • Halogen, carbamoyl, lower alkanol such as formyl, acetyl, propionyl, etc.
  • alk (lower) alkyl such as benzyl, methyl, ethyl, propyl, isopropyl, butyl, tert.
  • Lower alkyl groups such as tertiary butyl, for example, lower alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, and tertiary butoxycarbonyl, for example, alkoxycarbonyl groups such as benzyloxycarbonyl.
  • Groups, such as arylcarbonyl groups such as phenyloxycarbonyl Carboxy (lower) alkyl groups such as carboxymethyl and carboxyethyl, for example new paper Examples thereof include protected carboxy (lower) alkyl groups such as tert-butoxycarbonylmethyl.
  • lower alkylene group include straight-chain and branched-chain ones, for example, methylene group, ethylene group, trimethylene group, tetramethylene group, 1,1-dimethylethylene group, pentamethylene group. And hexamethylene groups, among which preferred examples include (C, -C,) alkylene groups, and more preferred examples include methylene group and ethylene group. .
  • m and n may be 0 in such a case. In this case, such a bond not via a lower alkylene group is formed.
  • phenyl, fluorine-containing phenyl as R 1 and R 2 hydrogen, hydroxyl, methyl and m as R 3. 0 or 1
  • a 1 is a methylene group
  • n is 0 or 1
  • a 2 is a methylene group or an ethylene group
  • R 5 s hydrogen, methyl, ethyl, isopropyl, imino protecting group
  • R 6 is ethyl Group
  • R 7 is hydrogen, methyl, ethyl, isopropyl, etc.
  • the compound (I) of the present invention and salts thereof have anticholinergic activity and are useful for treating urinary dysfunction in humans and animals, and other various diseases described above.
  • Compound (I) and salts thereof are characterized in that side effects such as mydriasis are reduced.
  • test compound was administered intravenously when the bladder contractile response to the water pressure load became constant.
  • the pharmaceutical composition of the present invention includes the compound (I) of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient, and can be administered rectally or pulmonary (nasally or nasally).
  • Suitable for oral inhalation), intranasal administration, ophthalmic administration, topical administration (topical administration), oral administration, parenteral administration (including subcutaneous administration, intravenous administration and intramuscular administration) or inhalation and intravesical administration Used as solid, semi-solid or liquid pharmaceutical preparations together with organic or inorganic carriers or excipients
  • the active ingredient is tablets, pellets, troches, capsules, suppositories, creams, ointments, aerosols It is formulated by mixing with, for example, a general-purpose non-toxic and pharmaceutically acceptable carrier for preparing inhalable powders, solutions, emulsions, suspensions, and other various forms suitable for use.
  • intravenous administration intramuscular administration
  • intrapulmonary administration oral administration and inhalation administration
  • the therapeutically effective dose of compound (I) will vary depending on the route of administration, age and symptoms of individual patients, etc.
  • Daily dose 0.01 to 2 Omg / kg to mice or animals, 0.1 to 20 mg / kg for intramuscular administration, and 0.5 to 50 rag / kg for oral administration. Or it is administered for therapeutic purposes.
  • New paper Sodium boride (32.7 g) was added in small portions. The obtained solution was stirred at room temperature for 1 hour, and the solvent was distilled off. Ethyl acetate (1 ⁇ ⁇ ) and water (500 ml) were added to the residue, and the organic layer was separated. This was washed successively with water (500 ml) and brine (500 ml), dried over magnesium sulfate, and the solvent was distilled off to obtain crude oily N— [1- (4-methoxybenzyl) 1-1,2, 3,6-Tetrahydropyridine-14-yl] methyl-12-hydroxy-2,2-diphenylacetic acid amide was obtained.
  • N [(1,2,3,6-tetrahydropyridin-141-methyl) methyl] —2—hydroxy-2,2-diphenylacetic acid amide (1.00 g) in 10% palladium on carbon in methanol
  • ASS (m / z): 183, 105, 91, 77
  • N— (1—Ethoxycarbonylbiperidine-1-4-yl) A solution of 1,2,2-diphenylacetic acid amide (4.00 g) and hydroxide (2.0 g) in methylcellulose sorb (30 ml) The mixture was heated and stirred for an hour. Ethyl acetate (100 ml) and water (300 ml) were added to the reaction mixture, and the mixture was separated. The aqueous layer was extracted with ethyl acetate (100 ml ⁇ 3), combined with the organic layer and the solvent was distilled off under reduced pressure. The residue was treated with a mixture of 4 N hydrochloric acid and ethyl acetate to obtain N- (piperidine-41-yl) -1,2,2-diphenylacetic acid amide hydrochloride.
  • Trimethylsilyl cyanide (1.35 ml) was added to a mixture of 4,4'-difluorobenzophenone (2. Og) and zinc iodide (0.1 lg) in anhydrous methylene chloride (15 ml) at room temperature. added. The obtained mixture was stirred at the same temperature for 40 hours, and the solvent was distilled off under reduced pressure. Concentrated hydrochloric acid (30 ml) was added to the residue, and the mixture was stirred at 90 ° C for 14 hours. Ethyl acetate and water were added to the reaction mixture for liquid separation, and the organic layer was separated and concentrated under reduced pressure.
  • N- (1-ethyl- 1,2,3,6-tetrahydropyridin-14-yl) methyl-2,2-diphenylpropionate amide hydrochloride (0.10 g ) was gotten.

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

Abstract

Composé anticholinergique répondant à la formule générale (I), dans laquelle R1 et R2 représentent chacun aryle éventuellement substitué, R3 représente hydrogène, hydroxy ou alkyle inférieur, R4 représente un groupe de la formule (a), (b), (c) ou (d), A1 et A2 représentent chacun alkylène inférieur, et m et n représentent chacun 0 ou 1.
PCT/JP1993/000142 1992-02-05 1993-02-04 Compose d'acetamide substitue WO1993016048A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9202443.9 1992-02-05
GB929202443A GB9202443D0 (en) 1992-02-05 1992-02-05 A novel substituted-acetamide compound and a process for the preparation thereof

Publications (1)

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WO1993016048A1 true WO1993016048A1 (fr) 1993-08-19

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GB (1) GB9202443D0 (fr)
WO (1) WO1993016048A1 (fr)

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WO1995006635A1 (fr) * 1993-09-02 1995-03-09 Yamanouchi Pharmaceutical Co., Ltd. Derive de carbamate et medicament le contenant
US5554613A (en) * 1992-06-04 1996-09-10 Zeneca Limited Heterocyclic derivatives
EP0751127A1 (fr) * 1995-06-26 1997-01-02 Ss Pharmaceutical Co., Ltd. 4-(.Alpha.-hydroxy-.alpha.-aryl-alkylcarbonylamino)-pipéridines pour le traitement et la prophylaxe des affections des voies urinaires
US5612352A (en) * 1992-04-10 1997-03-18 Zeneca Limited Heterocyclic compounds
US5691349A (en) * 1992-08-06 1997-11-25 Zeneca Limited Quinclidine derivatives as squalene synthase inhibitors
US5714496A (en) * 1992-08-28 1998-02-03 Zeneca Limited Quinuclidine derivatives as squalene synthase inhibitors
EP0801067A4 (fr) * 1994-12-28 1998-03-11 Yamanouchi Pharma Co Ltd Nouveaux derives de quinuclidine et composition pharmaceutique les contenant
US5731323A (en) * 1992-12-21 1998-03-24 Zeneca Limited Quinuclidine derivatives as squalene synthase inhibitors
US5792777A (en) * 1991-10-30 1998-08-11 Zeneca Limited Biphenyl quinuclidines
EP0823423A4 (fr) * 1995-04-28 1998-09-02 Banyu Pharma Co Ltd Derives disubstitues en position 1,4 de piperidine
EP0913393A3 (fr) * 1997-10-31 1999-05-26 SSP Co., Ltd. Dérivés d'arylacétamide, leur sels et leurs compositions pharmaceutiques
WO2000031078A1 (fr) * 1998-11-20 2000-06-02 Banyu Pharmaceutical Co., Ltd. Derives de 1-acetylazetidine
US6140333A (en) * 1998-02-04 2000-10-31 Banyu Pharmaceutical Co Ltd N-acyl cyclic amine derivatives
WO2004089898A1 (fr) * 2003-04-09 2004-10-21 Ranbaxy Laboratories Limited Derives d'azabicyclo hexane substitues en tant qu'antagonistes de recepteurs muscariniques
JP2005533826A (ja) * 2002-07-02 2005-11-10 アルミラール・プロデスファルマ・アクチェンゲゼルシャフト 新規なるキヌクリジンアミド誘導体
CN1298717C (zh) * 2000-12-22 2007-02-07 阿尔米雷尔普罗迪斯制药有限公司 奎宁环氨基甲酸酯衍生物及其作为m3拮抗剂的应用
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US7232835B2 (en) 2002-12-10 2007-06-19 Ranbaxy Laboratories Limited 3,6-Disubstituted azabicyclo derivatives as muscarinic receptor antagonists
US7265147B2 (en) 2002-07-31 2007-09-04 Ranbaxy Laboratories Limited 3,6-disubstituted azabicyclo [3.1.0]hexane derivatives useful as muscarinic receptor antagonists
US7288562B2 (en) 2002-08-23 2007-10-30 Ranbaxy Laboratories Limited Fluoro and sulphonylamino containing 3,6-disubstituted azabicyclo (3.1.0) hexane derivatives as muscarinic receptor antagonists
US7399779B2 (en) 2002-07-08 2008-07-15 Ranbaxy Laboratories Limited 3,6-disubstituted azabicyclo [3.1.0] hexane derivatives useful as muscarinic receptor antagonists
US7410993B2 (en) 2002-08-09 2008-08-12 Ranbaxy Laboratories Limited 3,6-disubstituted azabicyclo [3.1.0] hexane deriviatives useful as muscarinic receptor antagonists
US7446123B2 (en) 2003-04-11 2008-11-04 Ranbaxy Laboratories Limited Azabicyclo derivatives as muscarinic receptor antagonists
US7465751B2 (en) 2002-12-23 2008-12-16 Ranbaxy Laboratories Limited 1-substituted-3-pyrrolidine derivatives as muscarinic receptor antagonists
US7488748B2 (en) 2003-01-28 2009-02-10 Ranbaxy Laboratories Limited 3,6-Disubstituted azabicyclo hexane derivatives as muscarinic receptor antagonists
US7501443B2 (en) 2002-12-23 2009-03-10 Ranbaxy Laboratories Limited Flavaxate derivatives as muscarinic receptor antagonists
US7560479B2 (en) 2003-04-10 2009-07-14 Ranbaxy Laboratories Limited 3,6-Disubstituted azabicyclo hexane derivatives as muscarinic receptor antagonists
US7592359B2 (en) 2003-04-10 2009-09-22 Ranbaxy Laboratories Limited Substituted azabicyclo hexane derivatives as muscarinic receptor antagonists

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