NO309425B1 - Prokinetiske oksadiazoler - Google Patents

Prokinetiske oksadiazoler Download PDF

Info

Publication number: NO309425B1
Authority: NO; Norway
Prior art keywords: formula; radical; compounds; chloro; pharmaceutically acceptable
Prior art date: 1995-03-01

Application number

NO973808A

Other languages

English (en)

Norwegian (no)

Other versions

NO973808D0 (no

NO973808L (no

Inventor

Jean-Paul Rene Marie A Bosmans

Original Assignee

Janssen Pharmaceutica Nv

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.)

1995-03-01

Filing date

1997-08-19

Publication date

2001-01-29

1997-08-19 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1997-08-19 Publication of NO973808D0 publication Critical patent/NO973808D0/no

1997-08-19 Publication of NO973808L publication Critical patent/NO973808L/no

2001-01-29 Publication of NO309425B1 publication Critical patent/NO309425B1/no

Links

150000004866 oxadiazoles Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 58
239000000543 intermediate Substances 0.000 claims description 46
239000000203 mixture Substances 0.000 claims description 33
-1 sulfonyloxy Chemical group 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 18
239000000460 chlorine Substances 0.000 claims description 16
238000000034 method Methods 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
239000004480 active ingredient Substances 0.000 claims description 6
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 3
RUIOTASIGVZASR-UHFFFAOYSA-N 2-chloro-5-methoxy-4-[3-[1-(oxolan-2-ylmethyl)piperidin-4-yl]-1,2,4-oxadiazol-5-yl]aniline Chemical compound COC1=CC(N)=C(Cl)C=C1C1=NC(C2CCN(CC3OCCC3)CC2)=NO1 RUIOTASIGVZASR-UHFFFAOYSA-N 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
238000006243 chemical reaction Methods 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
RZZIKHSWRWWPAN-UHFFFAOYSA-N oxolane-2-carbonitrile Chemical compound N#CC1CCCO1 RZZIKHSWRWWPAN-UHFFFAOYSA-N 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
125000000815 N-oxide group Chemical group 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
125000000524 functional group Chemical group 0.000 claims 1
230000009466 transformation Effects 0.000 claims 1
239000000243 solution Substances 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
239000002904 solvent Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 16
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
150000003254 radicals Chemical class 0.000 description 13
241000282472 Canis lupus familiaris Species 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
150000001204 N-oxides Chemical group 0.000 description 8
238000004440 column chromatography Methods 0.000 description 8
239000003480 eluent Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
239000003826 tablet Substances 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
230000000968 intestinal effect Effects 0.000 description 6
230000004899 motility Effects 0.000 description 6
239000008194 pharmaceutical composition Substances 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
108091005482 5-HT4 receptors Proteins 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
239000002585 base Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
210000001072 colon Anatomy 0.000 description 4
230000004600 colonic motility Effects 0.000 description 4
108010037444 diisopropylglutathione ester Proteins 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
239000002464 receptor antagonist Substances 0.000 description 4
229940044551 receptor antagonist Drugs 0.000 description 4
230000004936 stimulating effect Effects 0.000 description 4
KRMUVKSAOVLXLF-UHFFFAOYSA-N 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound C1=C(Cl)C(N)=C2CCOC2=C1C(O)=O KRMUVKSAOVLXLF-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000000654 additive Substances 0.000 description 3
230000013872 defecation Effects 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000000725 suspension Substances 0.000 description 3
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 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
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 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
125000004448 alkyl carbonyl group Chemical group 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
230000000112 colonic effect Effects 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
230000008991 intestinal motility Effects 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000008101 lactose Substances 0.000 description 2
210000002429 large intestine Anatomy 0.000 description 2
239000007788 liquid Substances 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
229910000069 nitrogen hydride Inorganic materials 0.000 description 2
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
NNOQIGNUIUKVDJ-UHFFFAOYSA-N oxolan-2-ylmethyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CCCO1 NNOQIGNUIUKVDJ-UHFFFAOYSA-N 0.000 description 2
XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 2
239000006187 pill Substances 0.000 description 2
150000003053 piperidines Chemical class 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000010956 selective crystallization Methods 0.000 description 2
210000000813 small intestine Anatomy 0.000 description 2
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
239000012453 solvate Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000007910 systemic administration Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 1
OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
BQLHMMQUVJCTAN-UHFFFAOYSA-N 1-chloro-3-methoxypropane Chemical compound COCCCCl BQLHMMQUVJCTAN-UHFFFAOYSA-N 0.000 description 1
YGBXXWTZWLALGR-UHFFFAOYSA-N 2,3-Dimethylbenzofuran Chemical class C1=CC=C2C(C)=C(C)OC2=C1 YGBXXWTZWLALGR-UHFFFAOYSA-N 0.000 description 1
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
PLCAHSPIBBYHTP-UHFFFAOYSA-N 2-chloro-5-methoxy-4-(3-piperidin-4-yl-1,2,4-oxadiazol-5-yl)aniline Chemical compound COC1=CC(N)=C(Cl)C=C1C1=NC(C2CCNCC2)=NO1 PLCAHSPIBBYHTP-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
ALEHRPIPWUVBHE-UHFFFAOYSA-N 4-amino-5-chloro-2,2-dimethyl-3h-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=C(N)C2=C1OC(C)(C)C2 ALEHRPIPWUVBHE-UHFFFAOYSA-N 0.000 description 1
IRFAMQHXZRCJNR-UHFFFAOYSA-N 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carbonitrile Chemical compound C1=C(Cl)C(N)=C2CCOC2=C1C#N IRFAMQHXZRCJNR-UHFFFAOYSA-N 0.000 description 1
LXYQIWSECQYHAK-UHFFFAOYSA-N 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound NC(=O)C1=CC(Cl)=C(N)C2=C1OCC2 LXYQIWSECQYHAK-UHFFFAOYSA-N 0.000 description 1
VIIOKZIXRMTZFR-UHFFFAOYSA-N 4-amino-5-chloro-n'-hydroxy-2,3-dihydro-1-benzofuran-7-carboximidamide;hydrochloride Chemical compound Cl.O\N=C(/N)C1=CC(Cl)=C(N)C2=C1OCC2 VIIOKZIXRMTZFR-UHFFFAOYSA-N 0.000 description 1
CQPGDDAKTTWVDD-UHFFFAOYSA-N 4-bromobutanenitrile Chemical compound BrCCCC#N CQPGDDAKTTWVDD-UHFFFAOYSA-N 0.000 description 1
VMEOEAZFDMCCPM-UHFFFAOYSA-N 5-chloro-7-(5-piperidin-4-yl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1-benzofuran-4-amine Chemical compound C1=C(Cl)C(N)=C2CCOC2=C1C(N=1)=NOC=1C1CCNCC1 VMEOEAZFDMCCPM-UHFFFAOYSA-N 0.000 description 1
DEEDBTIONXNMJF-UHFFFAOYSA-N 5-chloro-7-[3-[1-(3-methoxypropyl)piperidin-4-yl]-1,2,4-oxadiazol-5-yl]-2,3-dihydro-1-benzofuran-4-amine Chemical compound C1CN(CCCOC)CCC1C1=NOC(C=2C=3OCCC=3C(N)=C(Cl)C=2)=N1 DEEDBTIONXNMJF-UHFFFAOYSA-N 0.000 description 1
OFEZPRVAKDLWEZ-UHFFFAOYSA-N 5-chloro-7-[3-[1-(3-methoxypropyl)piperidin-4-yl]-1,2,4-oxadiazol-5-yl]-2,3-dihydro-1-benzofuran-4-amine;hydrochloride Chemical compound Cl.C1CN(CCCOC)CCC1C1=NOC(C=2C=3OCCC=3C(N)=C(Cl)C=2)=N1 OFEZPRVAKDLWEZ-UHFFFAOYSA-N 0.000 description 1
BNEIDGWJPYYCOK-UHFFFAOYSA-N 5-chloro-7-[5-[1-(3-methoxypropyl)piperidin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1-benzofuran-4-amine Chemical compound C1CN(CCCOC)CCC1C1=NC(C=2C=3OCCC=3C(N)=C(Cl)C=2)=NO1 BNEIDGWJPYYCOK-UHFFFAOYSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
208000034657 Convalescence Diseases 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-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
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
235000002357 Ribes grossularia Nutrition 0.000 description 1
244000171263 Ribes grossularia Species 0.000 description 1
240000007651 Rubus glaucus Species 0.000 description 1
235000011034 Rubus glaucus Nutrition 0.000 description 1
235000009122 Rubus idaeus Nutrition 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000004974 alkaline earth metal peroxides Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical class C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000009835 boiling Methods 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
ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
238000006356 dehydrogenation reaction Methods 0.000 description 1
229940075894 denatured ethanol Drugs 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
MPGOGUUYMBFYCQ-UHFFFAOYSA-N ethyl 4-(n'-hydroxycarbamimidoyl)piperidine-1-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)N1CCC(C(N)=NO)CC1 MPGOGUUYMBFYCQ-UHFFFAOYSA-N 0.000 description 1
OHQOZQABIKTEFW-UHFFFAOYSA-N ethyl 4-[(e)-n'-hydroxycarbamimidoyl]piperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(C(N)=NO)CC1 OHQOZQABIKTEFW-UHFFFAOYSA-N 0.000 description 1
YPFOFWITOGFNHE-UHFFFAOYSA-N ethyl 4-[5-(4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-yl)-1,2,4-oxadiazol-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C1=NOC(C=2C=3OCCC=3C(N)=C(Cl)C=2)=N1 YPFOFWITOGFNHE-UHFFFAOYSA-N 0.000 description 1
PNADHFGKHRAQRX-UHFFFAOYSA-N ethyl 4-amino-5-chloro-2,2-dimethyl-3h-1-benzofuran-7-carboxylate Chemical compound CCOC(=O)C1=CC(Cl)=C(N)C2=C1OC(C)(C)C2 PNADHFGKHRAQRX-UHFFFAOYSA-N 0.000 description 1
HAPWNLVBWKCSLT-UHFFFAOYSA-N ethyl 4-cyanopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(C#N)CC1 HAPWNLVBWKCSLT-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
YSPVHAUJXLGZHP-UHFFFAOYSA-N ethyl piperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCCC1 YSPVHAUJXLGZHP-UHFFFAOYSA-N 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000000605 extraction Methods 0.000 description 1
210000003608 fece Anatomy 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
238000009472 formulation Methods 0.000 description 1
230000005176 gastrointestinal motility Effects 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
238000002695 general anesthesia Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
230000009931 harmful effect Effects 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
210000003767 ileocecal valve Anatomy 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VIKJMUYUUPEQNN-UHFFFAOYSA-N methyl 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carboxylate Chemical compound COC(=O)C1=CC(Cl)=C(N)C2=C1OCC2 VIKJMUYUUPEQNN-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
ITNXJLXLFAFOHO-UHFFFAOYSA-N n-piperidin-1-ylbenzamide Chemical class C=1C=CC=CC=1C(=O)NN1CCCCC1 ITNXJLXLFAFOHO-UHFFFAOYSA-N 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
229940100688 oral solution Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000001451 organic peroxides Chemical class 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000008855 peristalsis Effects 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Inorganic materials [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
239000001294 propane Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
239000008213 purified water Substances 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000001665 trituration Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- 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
- 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
- A61P1/10—Laxatives
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

NO973808A 1995-03-01 1997-08-19 Prokinetiske oksadiazoler NO309425B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP95200501		1995-03-01
PCT/EP1996/000784 WO1996026937A1 (en)	1995-03-01	1996-02-21	Prokinetic oxadiazoles

Publications (3)

Publication Number	Publication Date
NO973808D0 NO973808D0 (no)	1997-08-19
NO973808L NO973808L (no)	1997-08-19
NO309425B1 true NO309425B1 (no)	2001-01-29

Family

ID=8220055

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO973808A NO309425B1 (no)	1995-03-01	1997-08-19	Prokinetiske oksadiazoler

Country Status (25)

Country	Link
US (1)	US5854261A (pt)
EP (1)	EP0812321B1 (pt)
JP (1)	JP3980056B2 (pt)
KR (1)	KR100443554B1 (pt)
CN (1)	CN1092656C (pt)
AR (1)	AR003932A1 (pt)
AT (1)	ATE384716T1 (pt)
AU (1)	AU702932B2 (pt)
BR (1)	BR9607316A (pt)
CA (1)	CA2212893C (pt)
CZ (1)	CZ286992B6 (pt)
DE (1)	DE69637412T2 (pt)
EA (1)	EA001084B1 (pt)
ES (1)	ES2301166T3 (pt)
FI (1)	FI973562A0 (pt)
HU (1)	HUP9702395A3 (pt)
IL (1)	IL117315A (pt)
MY (1)	MY113584A (pt)
NO (1)	NO309425B1 (pt)
NZ (1)	NZ301699A (pt)
PL (1)	PL183712B1 (pt)
TR (1)	TR199700876T1 (pt)
TW (1)	TW360653B (pt)
WO (1)	WO1996026937A1 (pt)
ZA (1)	ZA961652B (pt)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9603755D0 (en) *	1996-02-22	1996-04-24	Pfizer Ltd	Therapeutic agents
US6107313A (en) *	1998-10-02	2000-08-22	Combichem, Inc.	Dopamine receptor antagonists
US7332508B2 (en) *	2002-12-18	2008-02-19	Novo Nordisk A/S	Substituted homopiperidine, piperidine or pyrrolidine derivatives
GB0910667D0 (en) *	2009-06-19	2009-08-05	Glaxo Wellcome Mfg Pte Ltd	Novel compounds
CN103380131B (zh) *	2011-09-19	2015-12-02	苏文生命科学有限公司	作为5-ht4受体配体的杂芳基化合物
CN117777121A (zh) *	2016-10-24	2024-03-29	詹森药业有限公司	化合物及其用途
WO2019084157A1 (en)	2017-10-24	2019-05-02	Yumanity Therapeutics, Inc.	COMPOUNDS AND USES THEREOF

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1183847A (en) *	1981-10-01	1985-03-12	Georges Van Daele	N-(3-hydroxy-4-piperidinyl)benzamide derivatives
US5374637A (en) *	1989-03-22	1994-12-20	Janssen Pharmaceutica N.V.	N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or dihydrobenzodioxin)carboxamide derivatives
GB9005014D0 (en) *	1990-03-06	1990-05-02	Janssen Pharmaceutica Nv	N.(4.piperidinyl)(dihydrobenzofuran or dihydro.2h.benzopyran)carboxamide derivatives
US5492919A (en) *	1991-08-03	1996-02-20	Smithkline Beecham P.L.C.	5-HT4 receptor antagonists
GB9202797D0 (en) *	1992-02-11	1992-03-25	Milsom Jonathan	Glazed units
US5708174A (en) *	1992-03-12	1998-01-13	Smithkline Beecham P.L.C.	Heterocyclic-esters or -amides used as 5-HT4 receptor antagonists
MX9306311A (es) *	1992-10-13	1994-04-29	Smithkline Beecham Plc	Compuestos antagonistas del receptor de 5-ht4, procedimiento para su preparacion y composiciones farmaceuticas que los contienen
CA2148700A1 (en) *	1992-11-05	1994-05-11	Laramie Mary Gaster	Piperidine derivatives as 5-ht4 receptor antagonists
JPH06157518A (ja) *	1992-11-27	1994-06-03	Yamanouchi Pharmaceut Co Ltd	新規なオキサジアゾール誘導体又はその塩
AU6856094A (en) *	1994-06-01	1995-12-21	Yamanouchi Pharmaceutical Co., Ltd.	Oxadiazole derivative and medicinal composition thereof

1996
- 1996-02-15 TW TW085101860A patent/TW360653B/zh not_active IP Right Cessation
- 1996-02-21 DE DE69637412T patent/DE69637412T2/de not_active Expired - Lifetime
- 1996-02-21 CZ CZ19972723A patent/CZ286992B6/cs not_active IP Right Cessation
- 1996-02-21 US US08/894,340 patent/US5854261A/en not_active Expired - Lifetime
- 1996-02-21 EA EA199700205A patent/EA001084B1/ru not_active IP Right Cessation
- 1996-02-21 EP EP96903000A patent/EP0812321B1/en not_active Expired - Lifetime
- 1996-02-21 AT AT96903000T patent/ATE384716T1/de not_active IP Right Cessation
- 1996-02-21 AU AU47188/96A patent/AU702932B2/en not_active Ceased
- 1996-02-21 KR KR1019970705701A patent/KR100443554B1/ko not_active IP Right Cessation
- 1996-02-21 WO PCT/EP1996/000784 patent/WO1996026937A1/en active IP Right Grant
- 1996-02-21 TR TR97/00876T patent/TR199700876T1/xx unknown
- 1996-02-21 BR BR9607316A patent/BR9607316A/pt not_active Application Discontinuation
- 1996-02-21 CA CA002212893A patent/CA2212893C/en not_active Expired - Lifetime
- 1996-02-21 HU HU9702395A patent/HUP9702395A3/hu unknown
- 1996-02-21 CN CN96192300A patent/CN1092656C/zh not_active Expired - Fee Related
- 1996-02-21 JP JP52601096A patent/JP3980056B2/ja not_active Expired - Lifetime
- 1996-02-21 NZ NZ301699A patent/NZ301699A/en not_active IP Right Cessation
- 1996-02-21 ES ES96903000T patent/ES2301166T3/es not_active Expired - Lifetime
- 1996-02-21 PL PL96322019A patent/PL183712B1/pl not_active IP Right Cessation
- 1996-02-29 MY MYPI96000748A patent/MY113584A/en unknown
- 1996-02-29 IL IL11731596A patent/IL117315A/xx not_active IP Right Cessation
- 1996-02-29 AR ARP960101592A patent/AR003932A1/es unknown
- 1996-02-29 ZA ZA9601652A patent/ZA961652B/xx unknown
1997
- 1997-08-19 NO NO973808A patent/NO309425B1/no not_active IP Right Cessation
- 1997-08-29 FI FI973562A patent/FI973562A0/fi not_active Application Discontinuation

Also Published As

Publication number	Publication date
NZ301699A (en)	1998-02-26
EP0812321A1 (en)	1997-12-17
US5854261A (en)	1998-12-29
ZA961652B (en)	1997-09-11
MY113584A (en)	2002-04-30
FI973562A (fi)	1997-08-29
JP3980056B2 (ja)	2007-09-19
HUP9702395A2 (hu)	1999-09-28
CA2212893A1 (en)	1996-09-06
HUP9702395A3 (en)	1999-10-28
CN1177352A (zh)	1998-03-25
EA199700205A1 (ru)	1998-02-26
NO973808D0 (no)	1997-08-19
FI973562A0 (fi)	1997-08-29
PL322019A1 (en)	1998-01-05
CZ286992B6 (en)	2000-08-16
CA2212893C (en)	2007-01-16
AR003932A1 (es)	1998-09-30
DE69637412D1 (de)	2008-03-13
NO973808L (no)	1997-08-19
IL117315A0 (en)	1996-06-18
TW360653B (en)	1999-06-11
EA001084B1 (ru)	2000-10-30
AU702932B2 (en)	1999-03-11
CZ272397A3 (cs)	1998-02-18
BR9607316A (pt)	1997-12-30
PL183712B1 (pl)	2002-07-31
WO1996026937A1 (en)	1996-09-06
JPH11501021A (ja)	1999-01-26
MX9706622A (es)	1997-11-29
EP0812321B1 (en)	2008-01-23
DE69637412T2 (de)	2009-01-22
TR199700876T1 (xx)	1998-02-21
CN1092656C (zh)	2002-10-16
ATE384716T1 (de)	2008-02-15
IL117315A (en)	2000-07-26
KR19980702304A (ko)	1998-07-15
AU4718896A (en)	1996-09-18
ES2301166T3 (es)	2008-06-16
KR100443554B1 (ko)	2004-10-06

Legal Events

Date	Code	Title	Description
2010-09-27	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
KR101799007B1 (ko)	2017-11-17	히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 설폰아마이드 유도체 화합물 및 이를 포함하는 약제학적 조성물
EP1076055B1 (en)	2004-11-24	1- (1-substituted-4-piperidinyl)methyl]-4-piperidine derivatives, process for producing the same, medicinal compositions containing the same and intermediates of these compounds
EP2183245B1 (en)	2014-07-09	Dual modulators of 5-ht2a and d3 receptors
EP1987019B1 (en)	2012-11-28	Benzoyl-piperidine derivatives as 5ht2/d3 modulators
US6498170B2 (en)	2002-12-24	Cyclamine sulfonamides as β-3 adrenergic receptor agonists
US8623859B2 (en)	2014-01-07	Bradykinin B1 antagonists
NO310232B1 (no)	2001-06-11	1-(1,2-disubstituert piperidinyl)-4-substituerte piperazinderivater
EP1501803A2 (en)	2005-02-02	Tetrahydropyranyl cyclopentyl tetrahydroisoquinoline modulators of chemokine receptor activity
EP1863763A1 (en)	2007-12-12	3,4,5-substituted piperidines as renin inhibitors
CA2954209A1 (en)	2016-02-04	2-oxa-5-azabicyclo[2.2.1]heptan-3-yl derivatives
NO309425B1 (no)	2001-01-29	Prokinetiske oksadiazoler
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