CA1078386A - 5-(1,1-diphenyl-3-(5-or 6-hydroxy-2-azabicyclo (2.2.2) oct-2-yl) propyl)-2-alkyl-1,3,4-oxadiazoles and related compounds - Google Patents
5-(1,1-diphenyl-3-(5-or 6-hydroxy-2-azabicyclo (2.2.2) oct-2-yl) propyl)-2-alkyl-1,3,4-oxadiazoles and related compoundsInfo
- Publication number
- CA1078386A CA1078386A CA273,594A CA273594A CA1078386A CA 1078386 A CA1078386 A CA 1078386A CA 273594 A CA273594 A CA 273594A CA 1078386 A CA1078386 A CA 1078386A
- Authority
- CA
- Canada
- Prior art keywords
- diphenyl
- oct
- propyl
- methyl
- azabicyclo
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 45
- -1 6-hydroxy-2-azabicyclo (2.2.2) oct-2-yl Chemical group 0.000 title abstract description 10
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 7
- 150000003536 tetrazoles Chemical class 0.000 claims abstract description 3
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims abstract 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 41
- 230000008569 process Effects 0.000 claims description 23
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 abstract description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 6
- 230000000202 analgesic effect Effects 0.000 abstract description 3
- 229940125714 antidiarrheal agent Drugs 0.000 abstract description 3
- 239000003793 antidiarrheal agent Substances 0.000 abstract description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 abstract 1
- 150000008064 anhydrides Chemical class 0.000 abstract 1
- 150000004866 oxadiazoles Chemical class 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 235000011121 sodium hydroxide Nutrition 0.000 description 10
- 229940083608 sodium hydroxide Drugs 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
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- 239000000284 extract Substances 0.000 description 6
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- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
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- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
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- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
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- 239000007789 gas Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000008159 sesame oil Substances 0.000 description 3
- 235000011803 sesame oil Nutrition 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- RHLVCLIPMVJYKS-UHFFFAOYSA-N 3-octanone Chemical compound CCCCCC(=O)CC RHLVCLIPMVJYKS-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000003810 Jones reagent Substances 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 230000001142 anti-diarrhea Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
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- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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- 230000004048 modification Effects 0.000 description 2
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
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- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 150000004862 dioxolanes Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- KOWWOODYPWDWOJ-LVBPXUMQSA-N elatine Chemical compound C([C@]12CN(C3[C@@]45OCO[C@]44[C@H]6[C@@H](OC)[C@@H]([C@H](C4)OC)C[C@H]6[C@@]3([C@@H]1[C@@H]5OC)[C@@H](OC)CC2)CC)OC(=O)C1=CC=CC=C1N1C(=O)CC(C)C1=O KOWWOODYPWDWOJ-LVBPXUMQSA-N 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- 239000001761 ethyl methyl cellulose Substances 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940074076 glycerol formal Drugs 0.000 description 1
- 235000020021 gose Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
- 239000010514 hydrogenated cottonseed oil Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- QCGKUFZYSPBMAY-UHFFFAOYSA-N methyl 7-oxabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1C(C(=O)OC)CCC2OC21 QCGKUFZYSPBMAY-UHFFFAOYSA-N 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- QQOXBFUTRLDXDP-UHFFFAOYSA-N p-Aminosalicylic acid methyl ester Chemical compound COC(=O)C1=CC=C(N)C=C1O QQOXBFUTRLDXDP-UHFFFAOYSA-N 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/38—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D303/40—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by ester radicals
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/665,609 US4013668A (en) | 1976-03-10 | 1976-03-10 | 5-(1,1-diphenyl-3-(5- or 6-hydroxy-2-azabicyclo(2.2.2)oct-2-yl)propyl)-2-alkyl-1,3,4-oxadiazoles and related compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1078386A true CA1078386A (en) | 1980-05-27 |
Family
ID=24670819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA273,594A Expired CA1078386A (en) | 1976-03-10 | 1977-03-09 | 5-(1,1-diphenyl-3-(5-or 6-hydroxy-2-azabicyclo (2.2.2) oct-2-yl) propyl)-2-alkyl-1,3,4-oxadiazoles and related compounds |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4013668A (enExample) |
| JP (1) | JPS5951955B2 (enExample) |
| AT (1) | AT350559B (enExample) |
| AU (1) | AU505650B2 (enExample) |
| BE (1) | BE852252A (enExample) |
| CA (1) | CA1078386A (enExample) |
| CH (1) | CH627467A5 (enExample) |
| DE (1) | DE2710242A1 (enExample) |
| DK (1) | DK103777A (enExample) |
| ES (1) | ES456687A1 (enExample) |
| FR (1) | FR2343740A2 (enExample) |
| GB (1) | GB1524653A (enExample) |
| IE (1) | IE44639B1 (enExample) |
| NL (1) | NL7702537A (enExample) |
| NZ (1) | NZ183540A (enExample) |
| SE (1) | SE7702640L (enExample) |
| ZA (1) | ZA771428B (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0241180A (ja) * | 1988-07-29 | 1990-02-09 | Shinji Kanda | 耐火避難用カプセル |
| DE69220258T2 (de) * | 1991-02-11 | 1997-12-18 | Merck Sharp & Dohme | Azabicyclische Verbindungen, diese enthaltende pharmazeutische Zubereitungen und ihre therapeutische Verwendung |
| US5962477A (en) * | 1994-04-12 | 1999-10-05 | Adolor Corporation | Screening methods for cytokine inhibitors |
| US6190691B1 (en) | 1994-04-12 | 2001-02-20 | Adolor Corporation | Methods for treating inflammatory conditions |
| US5849761A (en) * | 1995-09-12 | 1998-12-15 | Regents Of The University Of California | Peripherally active anti-hyperalgesic opiates |
| US6573282B1 (en) | 1995-09-12 | 2003-06-03 | Adolor Corporation | Peripherally active anti-hyperalgesic opiates |
| US5667773A (en) * | 1996-03-12 | 1997-09-16 | Adolor Corporation | Film-forming compositions of antihyperalgesic opiates and method of treating hyperalgesic conditions therewith |
| US6353004B1 (en) | 1997-07-14 | 2002-03-05 | Adolor Coporation | Peripherally acting anti-pruritic opiates |
| US20030158220A1 (en) * | 1997-11-03 | 2003-08-21 | Foss Joseph F. | Use of methylnaltrexone and related compounds to treat chronic opioid use side effects |
| PT1615646E (pt) * | 2003-04-08 | 2015-02-12 | Progenics Pharm Inc | Formulações farmacêuticas com metilnaltrexona |
| AR057035A1 (es) | 2005-05-25 | 2007-11-14 | Progenics Pharm Inc | SíNTESIS DE (R)-N-METILNALTREXONA, COMPOSICIONES FARMACÉUTICAS Y USOS |
| AR057325A1 (es) | 2005-05-25 | 2007-11-28 | Progenics Pharm Inc | Sintesis de (s)-n-metilnaltrexona, composiciones farmaceuticas y usos |
| TWI489984B (zh) | 2006-08-04 | 2015-07-01 | Wyeth Corp | 用於非經腸道傳輸化合物之配方及其用途 |
| TW200817048A (en) * | 2006-09-08 | 2008-04-16 | Wyeth Corp | Dry powder compound formulations and uses thereof |
| PT2565195E (pt) * | 2007-03-29 | 2015-07-28 | Wyeth Llc | Antagonistas e receptor opióide periférico e respectivas utilizações |
| PE20130480A1 (es) | 2007-03-29 | 2013-05-08 | Progenics Pharm Inc | Compuestos heterociclicos como antagonistas del receptor opioide periferico |
| MX2009010550A (es) * | 2007-03-29 | 2009-12-14 | Progenics Pharm Inc | Formas de cristal de bromuro de (r)-n-metilnaltrexona y uso de las mismas. |
| CA2713568C (en) | 2008-02-06 | 2016-09-20 | Progenics Pharmaceuticals, Inc. | Preparation and use of (r),(r)-2,2'-bis-methylnaltrexone |
| WO2010029313A1 (en) * | 2008-09-11 | 2010-03-18 | Summit Corporation Plc. | Antiinfective compounds |
| CA2676881C (en) | 2008-09-30 | 2017-04-25 | Wyeth | Peripheral opioid receptor antagonists and uses thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3917615A (en) * | 1974-04-01 | 1975-11-04 | Searle & Co | 1,1-Diaryl-1-oxadiazol-alkylamines |
-
1976
- 1976-03-10 US US05/665,609 patent/US4013668A/en not_active Expired - Lifetime
-
1977
- 1977-03-09 BE BE175614A patent/BE852252A/xx not_active IP Right Cessation
- 1977-03-09 AT AT157477A patent/AT350559B/de not_active IP Right Cessation
- 1977-03-09 CH CH295177A patent/CH627467A5/de not_active IP Right Cessation
- 1977-03-09 NL NL7702537A patent/NL7702537A/xx not_active Application Discontinuation
- 1977-03-09 NZ NZ183540A patent/NZ183540A/xx unknown
- 1977-03-09 IE IE515/77A patent/IE44639B1/en unknown
- 1977-03-09 SE SE7702640A patent/SE7702640L/xx unknown
- 1977-03-09 AU AU23029/77A patent/AU505650B2/en not_active Expired
- 1977-03-09 CA CA273,594A patent/CA1078386A/en not_active Expired
- 1977-03-09 ZA ZA00771428A patent/ZA771428B/xx unknown
- 1977-03-09 DK DK103777A patent/DK103777A/da unknown
- 1977-03-09 ES ES456687A patent/ES456687A1/es not_active Expired
- 1977-03-09 GB GB10031/77A patent/GB1524653A/en not_active Expired
- 1977-03-09 DE DE19772710242 patent/DE2710242A1/de not_active Withdrawn
- 1977-03-09 JP JP52025851A patent/JPS5951955B2/ja not_active Expired
- 1977-03-10 FR FR7707155A patent/FR2343740A2/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| DK103777A (da) | 1977-09-11 |
| FR2343740A2 (fr) | 1977-10-07 |
| US4013668A (en) | 1977-03-22 |
| IE44639B1 (en) | 1982-02-10 |
| JPS5951955B2 (ja) | 1984-12-17 |
| IE44639L (en) | 1977-09-10 |
| NZ183540A (en) | 1980-05-27 |
| ZA771428B (en) | 1978-10-25 |
| GB1524653A (en) | 1978-09-13 |
| ES456687A1 (es) | 1978-02-01 |
| SE7702640L (sv) | 1977-09-11 |
| CH627467A5 (de) | 1982-01-15 |
| AT350559B (de) | 1979-06-11 |
| JPS52108999A (en) | 1977-09-12 |
| AU2302977A (en) | 1978-09-14 |
| FR2343740B2 (enExample) | 1980-06-20 |
| ATA157477A (de) | 1978-11-15 |
| NL7702537A (nl) | 1977-09-13 |
| AU505650B2 (en) | 1979-11-29 |
| DE2710242A1 (de) | 1977-09-22 |
| BE852252A (fr) | 1977-09-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |