CA1067498A - 5-(1,1-diphenyl-3-(4-hydroxy-4-phenylpiperidino) propyl-2-methyl-1,3,4-alkadiazole compounds - Google Patents
5-(1,1-diphenyl-3-(4-hydroxy-4-phenylpiperidino) propyl-2-methyl-1,3,4-alkadiazole compoundsInfo
- Publication number
- CA1067498A CA1067498A CA223,485A CA223485A CA1067498A CA 1067498 A CA1067498 A CA 1067498A CA 223485 A CA223485 A CA 223485A CA 1067498 A CA1067498 A CA 1067498A
- Authority
- CA
- Canada
- Prior art keywords
- diphenyl
- propyl
- hydroxy
- methyl
- carbon atoms
- 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 24
- 150000008064 anhydrides Chemical class 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 23
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- -1 5-{1,1-diphenyl-3-[4-hydroxy-4-(4-chlorophenyl)piperidino]propyl}-1H-tetrazole Chemical compound 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 150000002440 hydroxy compounds Chemical class 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- CYIGQSPICYMIRV-UHFFFAOYSA-N 1-[3,3-diphenyl-3-(2h-tetrazol-5-yl)propyl]-4-phenylpiperidin-4-ol Chemical compound C1CC(O)(C=2C=CC=CC=2)CCN1CCC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1N=NNN=1 CYIGQSPICYMIRV-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- FMPVGXVHNVGVQJ-UHFFFAOYSA-N [1-[3-(5-methyl-1,3,4-oxadiazol-2-yl)-3,3-diphenylpropyl]-4-phenylpiperidin-4-yl] acetate Chemical compound C1(=CC=CC=C1)C(CCN1CCC(CC1)(C1=CC=CC=C1)OC(C)=O)(C1=CC=CC=C1)C1=NN=C(O1)C FMPVGXVHNVGVQJ-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 4
- 230000001142 anti-diarrhea Effects 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 3
- 150000003536 tetrazoles Chemical class 0.000 abstract description 3
- 230000005176 gastrointestinal motility Effects 0.000 abstract description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 abstract 1
- 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
- 230000036592 analgesia Effects 0.000 abstract 1
- 150000004866 oxadiazoles Chemical class 0.000 abstract 1
- 230000003389 potentiating effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 239000003610 charcoal Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000001506 calcium phosphate Substances 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
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 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
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- ZMSIFDIKIXVLDF-UHFFFAOYSA-N 2-methyl-1,3,4-oxadiazole Chemical compound CC1=NN=CO1 ZMSIFDIKIXVLDF-UHFFFAOYSA-N 0.000 description 1
- OTIRSAHHBSNELX-UHFFFAOYSA-N 4-(4-hydroxy-4-phenylpiperidin-1-yl)-2,2-diphenylbutanenitrile Chemical compound C1CC(O)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 OTIRSAHHBSNELX-UHFFFAOYSA-N 0.000 description 1
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940106135 cellulose Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical class CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 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
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- CZPRKINNVBONSF-UHFFFAOYSA-M zinc;dioxido(oxo)phosphanium Chemical compound [Zn+2].[O-][P+]([O-])=O CZPRKINNVBONSF-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- C07D211/30—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 doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—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 doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen 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
- C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US456755A US3917615A (en) | 1974-04-01 | 1974-04-01 | 1,1-Diaryl-1-oxadiazol-alkylamines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1067498A true CA1067498A (en) | 1979-12-04 |
Family
ID=23814026
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA223,485A Expired CA1067498A (en) | 1974-04-01 | 1975-04-01 | 5-(1,1-diphenyl-3-(4-hydroxy-4-phenylpiperidino) propyl-2-methyl-1,3,4-alkadiazole compounds |
| CA223,487A Expired CA1053672A (en) | 1974-04-01 | 1975-04-01 | 1,1-diaryl-1-oxadiazol-alkylamines |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA223,487A Expired CA1053672A (en) | 1974-04-01 | 1975-04-01 | 1,1-diaryl-1-oxadiazol-alkylamines |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US3917615A (en:Method) |
| JP (2) | JPS5936631B2 (en:Method) |
| AR (2) | AR206425A1 (en:Method) |
| AT (2) | AT342045B (en:Method) |
| BE (2) | BE827324A (en:Method) |
| CA (2) | CA1067498A (en:Method) |
| CH (2) | CH613964A5 (en:Method) |
| CS (1) | CS194718B2 (en:Method) |
| DE (2) | DE2514183A1 (en:Method) |
| DK (2) | DK137275A (en:Method) |
| EG (1) | EG12104A (en:Method) |
| ES (2) | ES436044A1 (en:Method) |
| FI (2) | FI63572C (en:Method) |
| FR (2) | FR2265367B1 (en:Method) |
| GB (2) | GB1494943A (en:Method) |
| HU (1) | HU170747B (en:Method) |
| IE (2) | IE40894B1 (en:Method) |
| IL (2) | IL46959A (en:Method) |
| NL (2) | NL7503856A (en:Method) |
| NO (2) | NO142173C (en:Method) |
| OA (1) | OA04914A (en:Method) |
| PH (1) | PH11423A (en:Method) |
| PL (1) | PL99553B1 (en:Method) |
| SE (2) | SE420492B (en:Method) |
| YU (1) | YU39200B (en:Method) |
| ZA (2) | ZA751193B (en:Method) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4003904A (en) * | 1974-04-01 | 1977-01-18 | G. D. Searle & Co. | Anti-diarrheal oxadiazoles |
| US4086227A (en) * | 1975-04-16 | 1978-04-25 | G. D. Searle & Co. | Novel anti-diarrheal 4-azatricyclo[4.3.1.13,8 ] undecane derivatives |
| US3998832A (en) * | 1975-04-16 | 1976-12-21 | G. D. Searle & Co. | Anti-diarrheal compounds |
| US4057549A (en) * | 1975-04-16 | 1977-11-08 | G. D. Searle & Co. | Triarylpropyl-azabicyclooctanes |
| US4025524A (en) * | 1975-04-16 | 1977-05-24 | G. D. Searle & Co. | 2-{3-[4-Azatricyclo(4.3.1.13,8)undecan-4-yl]-1,1-diphenylpropyl}-5-methyl-1,3,4-oxadiazole and congeners |
| US3996214A (en) * | 1976-02-23 | 1976-12-07 | G. D. Searle & Co. | 5-(1,1-Diphenyl-4-(cyclic amino) but-2-trans-en-1-yl)-2-alkyl-1,3,4-oxadiazoles and intermediates thereto |
| US4013668A (en) * | 1976-03-10 | 1977-03-22 | G. D. Searle & Co. | 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 |
| US4012393A (en) * | 1976-03-22 | 1977-03-15 | G. D. Searle & Co. | 2-[5-(CYCLIC AMINO) ETHYL-10,11-DIHYDRO-5H-dibenzo[a,d]-cyclohepten-5- yl]-5 |
| US4028364A (en) * | 1976-07-06 | 1977-06-07 | G. D. Searle & Co. | 2-Azabicyclo[2.2.2.]octan-2-yl-diphenyl-alkanones and related compounds |
| US4053477A (en) * | 1976-09-20 | 1977-10-11 | G. D. Searle & Co. | 5-(1,1-diphenyl-3-(4-phenylpiperidino)propyl)-2-methyl-1,3,4-oxadiazole and related compounds |
| US4194045A (en) * | 1977-12-27 | 1980-03-18 | G. D. Searle & Co. | 1-(3,3-Diaryl-3-oxadiazolalkyl)-4-phenyl-4-piperidinomethanols and related compounds |
| US4203989A (en) * | 1979-04-30 | 1980-05-20 | G. D. Searle & Co. | Anti-diarrheal diaryl-(1-azabicyclo(2.2.2)octan-2-yl)-alkanols and related compounds |
| US4203990A (en) * | 1979-04-30 | 1980-05-20 | G. D. Searle & Co. | Anti-diarrheal 2-substituted quinuclidines |
| US4596801A (en) | 1983-03-24 | 1986-06-24 | Chugai Seiyaku Kabushiki Kaisha | 4H-3,1-benzoxazine derivatives, process for producing the same and agricultural or horticultural fungicide containing the same |
| JPS61194917A (ja) * | 1985-02-23 | 1986-08-29 | Matsushita Electric Works Ltd | 遅れスイツチ |
| JPS61195022A (ja) * | 1985-02-25 | 1986-08-29 | Matsushita Electric Works Ltd | 遅れスイツチ |
| GB8830226D0 (en) * | 1988-12-23 | 1989-02-22 | Beecham Group Plc | Novel compounds |
| DK40890D0 (da) * | 1990-02-16 | 1990-02-16 | Ferrosan As | Substituerede urinstofforbindelser, deres fremstilling og anvendelse |
| US5889038A (en) * | 1996-03-20 | 1999-03-30 | Children's Hospital | Methods and products for treating diarrhea and scours: use of clotrimazole and related aromatic compounds |
| PT2012164573W (pt) | 2011-05-27 | 2014-10-08 | Reliance Ind Ltd | Procedimento para a preparação de um ácido carboxílico orgânico por hidrólise de um ester de ácido carboxílico orgânico |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3141019A (en) * | 1964-07-14 | Chaohj | ||
| US3299044A (en) * | 1964-05-13 | 1967-01-17 | Searle & Co | Complex n-substituted azabicycloalkanes |
| FR1469022A (fr) * | 1965-12-14 | 1967-02-10 | Chimie Et Synthese De Picardie | Nouveaux dérivés oxadiazoliques et leur procédé de préparation |
| GB1174411A (en) * | 1966-03-02 | 1969-12-17 | Aspro Nicholas Ltd | Novel Benzothiophen Compounds, Compositions containing them and processes for their manufacture |
| GB1231829A (en:Method) * | 1968-09-19 | 1971-05-12 | ||
| US3720685A (en) * | 1970-07-15 | 1973-03-13 | Squibb & Sons Inc | 3-amino-5-benzyl-1,2,4-oxadiazoles |
-
1974
- 1974-04-01 US US456755A patent/US3917615A/en not_active Expired - Lifetime
-
1975
- 1975-01-01 AR AR258169A patent/AR206425A1/es active
- 1975-02-26 ZA ZA00751193A patent/ZA751193B/xx unknown
- 1975-03-26 ES ES436044A patent/ES436044A1/es not_active Expired
- 1975-03-28 CS CS752162A patent/CS194718B2/cs unknown
- 1975-03-28 FR FR7509995A patent/FR2265367B1/fr not_active Expired
- 1975-03-28 IL IL46959A patent/IL46959A/xx unknown
- 1975-03-28 BE BE154890A patent/BE827324A/xx not_active IP Right Cessation
- 1975-03-28 HU HUSE1776A patent/HU170747B/hu unknown
- 1975-03-28 FR FR7509996A patent/FR2265376B1/fr not_active Expired
- 1975-03-28 BE BE154889A patent/BE827323A/xx not_active IP Right Cessation
- 1975-03-31 JP JP50039025A patent/JPS5936631B2/ja not_active Expired
- 1975-03-31 JP JP50039024A patent/JPS5939434B2/ja not_active Expired
- 1975-03-31 ES ES436160A patent/ES436160A1/es not_active Expired
- 1975-03-31 OA OA55456A patent/OA04914A/xx unknown
- 1975-03-31 YU YU00816/75A patent/YU39200B/xx unknown
- 1975-03-31 IL IL46966A patent/IL46966A/en unknown
- 1975-03-31 EG EG179/75A patent/EG12104A/xx active
- 1975-03-31 PH PH16986A patent/PH11423A/en unknown
- 1975-04-01 CH CH410875A patent/CH613964A5/xx not_active IP Right Cessation
- 1975-04-01 CA CA223,485A patent/CA1067498A/en not_active Expired
- 1975-04-01 FI FI750965A patent/FI63572C/fi not_active IP Right Cessation
- 1975-04-01 GB GB13184/75A patent/GB1494943A/en not_active Expired
- 1975-04-01 DK DK137275A patent/DK137275A/da not_active IP Right Cessation
- 1975-04-01 NL NL7503856A patent/NL7503856A/xx not_active Application Discontinuation
- 1975-04-01 NO NO751103A patent/NO142173C/no unknown
- 1975-04-01 DE DE19752514183 patent/DE2514183A1/de not_active Withdrawn
- 1975-04-01 PL PL1975179255A patent/PL99553B1/pl unknown
- 1975-04-01 CH CH410975A patent/CH614205A5/xx not_active IP Right Cessation
- 1975-04-01 GB GB1318675A patent/GB1456943A/en not_active Expired
- 1975-04-01 FI FI750966A patent/FI61895C/fi not_active IP Right Cessation
- 1975-04-01 DE DE19752514229 patent/DE2514229A1/de not_active Ceased
- 1975-04-01 DK DK137375A patent/DK137375A/da not_active Application Discontinuation
- 1975-04-01 NL NL7503849A patent/NL7503849A/xx not_active Application Discontinuation
- 1975-04-01 CA CA223,487A patent/CA1053672A/en not_active Expired
- 1975-04-01 AT AT245275A patent/AT342045B/de not_active IP Right Cessation
- 1975-04-01 ZA ZA00751986A patent/ZA751986B/xx unknown
- 1975-04-01 SE SE7503689A patent/SE420492B/xx unknown
- 1975-04-01 SE SE7503688A patent/SE420491B/xx not_active IP Right Cessation
- 1975-04-01 AT AT245175A patent/AT340916B/de not_active IP Right Cessation
- 1975-04-01 NO NO751104A patent/NO142174C/no unknown
- 1975-04-02 IE IE712/75A patent/IE40894B1/xx unknown
- 1975-04-02 IE IE713/75A patent/IE40895B1/xx unknown
-
1976
- 1976-07-15 AR AR20634176D patent/AR206341A1/es active
- 1976-09-02 US US05/719,775 patent/USRE29556E/en not_active Expired - Lifetime
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