SK121397A3 - Di-substituted 1,4-piperidine esters and amides having 5-ht4 antagonistic activity, producing method and their use - Google Patents

Di-substituted 1,4-piperidine esters and amides having 5-ht4 antagonistic activity, producing method and their use Download PDF

Info

Publication number: SK121397A3
Authority: SK; Slovakia
Prior art keywords: formula; piperidin; compound; amino; solvent
Prior art date: 1995-03-14

Application number

SK1213-97A

Other languages

English (en)

Slovak (sk)

Inventor

Enzo Cereda

Maura Bignotti

Vincenzo Martino

Giovanni B Schiavi

Angelo Sagrada

Original Assignee

Boehringer Ingelheim Italia

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.)

1995-03-14

Filing date

1996-03-04

Publication date

1998-02-04

1996-03-04 Application filed by Boehringer Ingelheim Italia filed Critical Boehringer Ingelheim Italia

1998-02-04 Publication of SK121397A3 publication Critical patent/SK121397A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 55
150000001408 amides Chemical class 0.000 title abstract description 5
FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical class FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 title abstract description 4
230000003042 antagnostic effect Effects 0.000 title description 3
230000008569 process Effects 0.000 claims abstract description 19
238000002360 preparation method Methods 0.000 claims abstract description 16
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
150000001875 compounds Chemical class 0.000 claims description 98
-1 hydroxy, benzyloxy, methylthiomethyl Chemical group 0.000 claims description 85
239000002904 solvent Substances 0.000 claims description 34
229910052739 hydrogen Inorganic materials 0.000 claims description 23
239000001257 hydrogen Substances 0.000 claims description 22
238000006243 chemical reaction Methods 0.000 claims description 20
239000000203 mixture Substances 0.000 claims description 20
239000002243 precursor Substances 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 17
238000010992 reflux Methods 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
239000012442 inert solvent Substances 0.000 claims description 12
239000004480 active ingredient Substances 0.000 claims description 11
239000012948 isocyanate Substances 0.000 claims description 11
150000002513 isocyanates Chemical class 0.000 claims description 11
AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 10
150000002431 hydrogen Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
239000001301 oxygen Substances 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
230000009467 reduction Effects 0.000 claims description 7
238000011282 treatment Methods 0.000 claims description 7
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 claims description 5
150000007513 acids Chemical class 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
238000005915 ammonolysis reaction Methods 0.000 claims description 5
125000003710 aryl alkyl group Chemical group 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
208000035475 disorder Diseases 0.000 claims description 4
125000001041 indolyl group Chemical group 0.000 claims description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
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208000007848 Alcoholism Diseases 0.000 claims description 3
208000019901 Anxiety disease Diseases 0.000 claims description 3
208000019695 Migraine disease Diseases 0.000 claims description 3
208000028017 Psychotic disease Diseases 0.000 claims description 3
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230000000747 cardiac effect Effects 0.000 claims description 3
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125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
229940098779 methanesulfonic acid Drugs 0.000 claims description 3
206010027599 migraine Diseases 0.000 claims description 3
239000012454 non-polar solvent Substances 0.000 claims description 3
150000007530 organic bases Chemical class 0.000 claims description 3
208000016285 Movement disease Diseases 0.000 claims description 2
239000000969 carrier Substances 0.000 claims description 2
230000033764 rhythmic process Effects 0.000 claims description 2
125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
239000003586 protic polar solvent Substances 0.000 claims 2
229910021529 ammonia Inorganic materials 0.000 claims 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
230000008030 elimination Effects 0.000 claims 1
238000003379 elimination reaction Methods 0.000 claims 1
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239000003523 serotonin 4 antagonist Substances 0.000 abstract description 3
150000002148 esters Chemical class 0.000 abstract description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 112
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
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 84
239000000243 solution Substances 0.000 description 79
230000008018 melting Effects 0.000 description 51
238000002844 melting Methods 0.000 description 51
238000004458 analytical method Methods 0.000 description 44
238000001819 mass spectrum Methods 0.000 description 39
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239000000460 chlorine Substances 0.000 description 32
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
239000000543 intermediate Substances 0.000 description 23
239000011541 reaction mixture Substances 0.000 description 23
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
239000003480 eluent Substances 0.000 description 19
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
108020003175 receptors Proteins 0.000 description 17
102000005962 receptors Human genes 0.000 description 17
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 17
239000007864 aqueous solution Substances 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
150000001412 amines Chemical class 0.000 description 11
238000004587 chromatography analysis Methods 0.000 description 11
239000011734 sodium Substances 0.000 description 11
238000003756 stirring Methods 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
229910000085 borane Inorganic materials 0.000 description 9
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
239000007789 gas Substances 0.000 description 9
230000008020 evaporation Effects 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
239000000725 suspension Substances 0.000 description 8
229940024606 amino acid Drugs 0.000 description 7
150000001413 amino acids Chemical class 0.000 description 7
238000011097 chromatography purification Methods 0.000 description 7
238000009472 formulation Methods 0.000 description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
RVEATKYEARPWRE-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(N)=C(Cl)C=C1C(O)=O RVEATKYEARPWRE-UHFFFAOYSA-N 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
239000013543 active substance Substances 0.000 description 6
150000004657 carbamic acid derivatives Chemical class 0.000 description 6
238000010511 deprotection reaction Methods 0.000 description 6
230000000694 effects Effects 0.000 description 6
IMJMKKJFVNMUQR-UHFFFAOYSA-N 3-ethyl-2-oxobenzimidazole-1-carboxamide Chemical compound C1=CC=C2N(C(N)=O)C(=O)N(CC)C2=C1 IMJMKKJFVNMUQR-UHFFFAOYSA-N 0.000 description 5
108091005482 5-HT4 receptors Proteins 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
XWQRAGBOSRDHGZ-UHFFFAOYSA-N carbazole-9-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)C3=CC=CC=C3C2=C1 XWQRAGBOSRDHGZ-UHFFFAOYSA-N 0.000 description 5
HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 5
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QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
RRJGZTSNHOTHBH-UHFFFAOYSA-N 2-oxo-3-propan-2-ylbenzimidazole-1-carboxamide Chemical compound C1=CC=C2N(C(N)=O)C(=O)N(C(C)C)C2=C1 RRJGZTSNHOTHBH-UHFFFAOYSA-N 0.000 description 3
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230000003287 optical effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
XLZLKQFDGZGABV-UHFFFAOYSA-N piperidin-4-yl 1-methylindole-2-carboxylate Chemical compound C=1C2=CC=CC=C2N(C)C=1C(=O)OC1CCNCC1 XLZLKQFDGZGABV-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
230000008092 positive effect Effects 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000011946 reduction process Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
238000007789 sealing Methods 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000003727 serotonin 1A antagonist Substances 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000007962 solid dispersion Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000009469 supplementation Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
PIIHCKJOVUBHBY-UHFFFAOYSA-N tert-butyl N-[5-(4-carbamoylpiperidin-1-yl)-5-sulfanylidenepentan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(=O)NC(CCC(=S)N1CCC(CC1)C(N)=O)C PIIHCKJOVUBHBY-UHFFFAOYSA-N 0.000 description 1
ZLYSCIKPAYJQAT-UHFFFAOYSA-N tert-butyl n-[1-[4-(hydroxymethyl)piperidin-1-yl]-1-oxo-3-phenylmethoxypropan-2-yl]carbamate Chemical compound C1CC(CO)CCN1C(=O)C(NC(=O)OC(C)(C)C)COCC1=CC=CC=C1 ZLYSCIKPAYJQAT-UHFFFAOYSA-N 0.000 description 1
BYQJEOJFVRRMRX-UHFFFAOYSA-N tert-butyl n-[3-(4-carbamoylpiperidin-1-yl)-1-phenylmethoxypropyl]carbamate Chemical compound C=1C=CC=CC=1COC(NC(=O)OC(C)(C)C)CCN1CCC(C(N)=O)CC1 BYQJEOJFVRRMRX-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
229920003169 water-soluble polymer Polymers 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- C07D211/20—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 singly bound oxygen or sulphur atoms
- C07D211/22—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 singly bound oxygen or sulphur atoms by oxygen atoms
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- A61P25/24—Antidepressants
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Addiction (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)

SK1213-97A 1995-03-14 1996-03-04 Di-substituted 1,4-piperidine esters and amides having 5-ht4 antagonistic activity, producing method and their use SK121397A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IT95MI000491A IT1275903B1 (it)	1995-03-14	1995-03-14	Esteri e ammidi della 1,4-piperidina disostituita
PCT/EP1996/000903 WO1996028424A1 (en)	1995-03-14	1996-03-04	Di-substituted 1,4-piperidine esters and amides having 5-ht4 antagonistic activity

Publications (1)

Publication Number	Publication Date
SK121397A3 true SK121397A3 (en)	1998-02-04

Family

ID=11370883

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1213-97A SK121397A3 (en)	1995-03-14	1996-03-04	Di-substituted 1,4-piperidine esters and amides having 5-ht4 antagonistic activity, producing method and their use

Country Status (27)

Country	Link
US (1)	US6002009A (it)
EP (1)	EP0815080B1 (it)
JP (1)	JP4021477B2 (it)
KR (1)	KR19980702972A (it)
AR (1)	AR002967A1 (it)
AT (1)	ATE269304T1 (it)
AU (1)	AU5101096A (it)
BG (1)	BG101711A (it)
BR (1)	BR9607347A (it)
CA (1)	CA2209904C (it)
CO (1)	CO4700521A1 (it)
CZ (1)	CZ285997A3 (it)
DE (1)	DE69632724T2 (it)
EE (1)	EE9700202A (it)
ES (1)	ES2224159T3 (it)
HR (1)	HRP960116A2 (it)
IL (1)	IL117446A0 (it)
IT (1)	IT1275903B1 (it)
NO (1)	NO974236D0 (it)
NZ (1)	NZ303941A (it)
PE (1)	PE7698A1 (it)
PL (1)	PL322211A1 (it)
SK (1)	SK121397A3 (it)
TR (1)	TR199700948T1 (it)
WO (1)	WO1996028424A1 (it)
YU (1)	YU14196A (it)
ZA (1)	ZA962009B (it)

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ES2164151T3 (es) *	1995-06-06	2002-02-16	Pfizer	N-(indol-2-carbonil)glicinamidas sustituidas y derivados como inhibidores de la glucogeno fosforilasa.
AU7001796A (en) *	1995-09-22	1997-04-09	Yoshitomi Pharmaceutical Industries, Ltd.	Benzoic acid compounds and medicinal use thereof
TW445263B (en)	1996-02-29	2001-07-11	Janssen Pharmaceutica Nv	Novel esters of 1,4-disubstituted piperidine derivatives
US6339087B1 (en)	1997-08-18	2002-01-15	Syntex (U.S.A.) Llc	Cyclic amine derivatives-CCR-3 receptor antagonists
IL125658A0 (en)	1997-08-18	1999-04-11	Hoffmann La Roche	Ccr-3 receptor antagonists
TW570920B (en)	1998-12-22	2004-01-11	Janssen Pharmaceutica Nv	4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders
GB0211230D0 (en) *	2002-05-16	2002-06-26	Medinnova Sf	Treatment of heart failure
CA2537127C (en) *	2003-09-03	2011-04-05	Pfizer Inc.	Benzimidazolone compounds having 5-ht4 receptor agonistic activity
TW200533348A (en) *	2004-02-18	2005-10-16	Theravance Inc	Indazole-carboxamide compounds as 5-ht4 receptor agonists
US7728006B2 (en) *	2004-04-07	2010-06-01	Theravance, Inc.	Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
US8309575B2 (en)	2004-04-07	2012-11-13	Theravance, Inc.	Quinolinone-carboxamide compounds as 5-HT4 receptor agonists
TWI351282B (en)	2004-04-07	2011-11-01	Theravance Inc	Quinolinone-carboxamide compounds as 5-ht4 recepto
AU2005254800B2 (en) *	2004-06-15	2010-12-09	Pfizer Inc.	Benzimidazolone carboxylic acid derivatives
US7737163B2 (en) *	2004-06-15	2010-06-15	Pfizer Inc.	Benzimidazolone carboxylic acid derivatives
AP2418A (en) *	2004-06-15	2012-06-04	Pfizer	Benzimidazolone carboxylic acid derivatives.
JP2008509088A (ja) *	2004-09-02	2008-03-27	ファイザー株式会社	ベンズイミダゾロンカルボン酸誘導体
JP5042028B2 (ja) *	2004-11-05	2012-10-03	セラヴァンス，インコーポレーテッド	キノリノン−カルボキサミド化合物
DE602005016446D1 (de) *	2004-11-05	2009-10-15	Theravance Inc	5-HT4-Rezeptoragonistenverbindungen
KR20070091665A (ko) *	2004-12-22	2007-09-11	세라밴스 인코포레이티드	인다졸－카르복사미드 화합물
NZ556627A (en) *	2005-02-22	2010-09-30	Pfizer	Oxyindole derivatives as 5HT4 receptor agonists
WO2006094063A1 (en) *	2005-03-02	2006-09-08	Theravance, Inc.	Quinolinone compounds as 5-ht4 receptor agonists
ES2359673T3 (es) *	2005-06-07	2011-05-25	Theravance, Inc.	Compuestos de benzoimidazolona-carboxamida como agonista del receptor 5-ht4.
MY143574A (en) *	2005-11-22	2011-05-31	Theravance Inc	Carbamate compounds as 5-ht4 receptor agonists
US8642772B2 (en)	2008-10-14	2014-02-04	Sk Biopharmaceuticals Co., Ltd.	Piperidine compounds, pharmaceutical composition comprising the same and its use
US8232315B2 (en) *	2009-06-26	2012-07-31	Sk Biopharmaceuticals Co., Ltd.	Methods for treating drug addiction and improving addiction-related behavior
KR101783632B1 (ko)	2009-11-06	2017-10-10	에스케이바이오팜 주식회사	주의력 결핍/과잉행동 장애(ａｄｈｄ)의 치료 방법
WO2011055944A2 (en)	2009-11-06	2011-05-12	Sk Holdings Co., Ltd.	Methods for treating fibromyalgia syndrome
WO2011163594A2 (en) *	2010-06-24	2011-12-29	Alkermes, Inc.	Prodrugs of nh-acidic compounds: ester, carbonate, carbamate and phosphonate derivatives
US9610274B2 (en)	2010-06-30	2017-04-04	Sk Biopharmaceuticals Co., Ltd.	Methods for treating bipolar disorder
US8623913B2 (en)	2010-06-30	2014-01-07	Sk Biopharmaceuticals Co., Ltd.	Methods for treating restless legs syndrome

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GB9103862D0 (en) *	1991-02-25	1991-04-10	Glaxo Group Ltd	Chemical compounds
GB9204565D0 (en) *	1992-03-03	1992-04-15	Smithkline Beecham Plc	Pharmaceuticals
EP0664794A1 (en) *	1992-10-16	1995-08-02	Smithkline Beecham Plc	N-alkylpiperidinyl-4-methyl carboxylic esters/amides of condensed ring systems as 5-ht4 receptor antagonists
EP0774460A1 (en) *	1994-03-30	1997-05-21	Yoshitomi Pharmaceutical Industries, Ltd.	Benzoic acid compound and use thereof as medicine

1995
- 1995-03-14 IT IT95MI000491A patent/IT1275903B1/it active IP Right Grant
1996
- 1996-03-04 CZ CZ972859A patent/CZ285997A3/cs unknown
- 1996-03-04 WO PCT/EP1996/000903 patent/WO1996028424A1/en not_active Ceased
- 1996-03-04 ES ES96907342T patent/ES2224159T3/es not_active Expired - Lifetime
- 1996-03-04 KR KR1019970706380A patent/KR19980702972A/ko not_active Withdrawn
- 1996-03-04 BR BR9607347A patent/BR9607347A/pt not_active Application Discontinuation
- 1996-03-04 CA CA002209904A patent/CA2209904C/en not_active Expired - Lifetime
- 1996-03-04 JP JP52723396A patent/JP4021477B2/ja not_active Expired - Lifetime
- 1996-03-04 DE DE69632724T patent/DE69632724T2/de not_active Expired - Lifetime
- 1996-03-04 AU AU51010/96A patent/AU5101096A/en not_active Abandoned
- 1996-03-04 NZ NZ303941A patent/NZ303941A/en unknown
- 1996-03-04 SK SK1213-97A patent/SK121397A3/sk unknown
- 1996-03-04 US US08/913,425 patent/US6002009A/en not_active Expired - Lifetime
- 1996-03-04 AT AT96907342T patent/ATE269304T1/de active
- 1996-03-04 PL PL96322211A patent/PL322211A1/xx unknown
- 1996-03-04 EE EE9700202A patent/EE9700202A/xx unknown
- 1996-03-04 TR TR97/00948T patent/TR199700948T1/xx unknown
- 1996-03-04 EP EP96907342A patent/EP0815080B1/en not_active Expired - Lifetime
- 1996-03-05 PE PE1996000151A patent/PE7698A1/es not_active Application Discontinuation
- 1996-03-08 AR ARP960101670A patent/AR002967A1/es unknown
- 1996-03-11 YU YU14196A patent/YU14196A/sh unknown
- 1996-03-12 IL IL11744696A patent/IL117446A0/xx unknown
- 1996-03-13 CO CO96012408A patent/CO4700521A1/es unknown
- 1996-03-13 ZA ZA9602009A patent/ZA962009B/xx unknown
- 1996-03-13 HR HRMI95A000491A patent/HRP960116A2/hr not_active Application Discontinuation
1997
- 1997-07-01 BG BG101711A patent/BG101711A/xx unknown
- 1997-09-12 NO NO974236A patent/NO974236D0/no unknown

Also Published As

Publication number	Publication date
DE69632724T2 (de)	2005-07-07
AU5101096A (en)	1996-10-02
EP0815080A1 (en)	1998-01-07
IT1275903B1 (it)	1997-10-24
JP4021477B2 (ja)	2007-12-12
ITMI950491A1 (it)	1996-09-14
JPH11501640A (ja)	1999-02-09
PE7698A1 (es)	1998-03-11
ITMI950491A0 (it)	1995-03-14
KR19980702972A (ko)	1998-09-05
CZ285997A3 (cs)	1998-02-18
US6002009A (en)	1999-12-14
NO974236L (no)	1997-09-12
CA2209904A1 (en)	1996-09-19
CA2209904C (en)	2007-11-13
MX9706826A (es)	1997-11-29
YU14196A (sh)	1999-03-04
ZA962009B (en)	1997-09-15
PL322211A1 (en)	1998-01-19
ATE269304T1 (de)	2004-07-15
BR9607347A (pt)	1997-12-30
EE9700202A (et)	1998-02-16
WO1996028424A1 (en)	1996-09-19
BG101711A (en)	1998-02-27
DE69632724D1 (de)	2004-07-22
EP0815080B1 (en)	2004-06-16
ES2224159T3 (es)	2005-03-01
NO974236D0 (no)	1997-09-12
HRP960116A2 (en)	1997-10-31
AR002967A1 (es)	1998-05-27
CO4700521A1 (es)	1998-12-29
NZ303941A (en)	1998-11-25
TR199700948T1 (xx)	1998-03-21
IL117446A0 (en)	1996-07-23

Publication	Publication Date	Title
EP0815080B1 (en)	2004-06-16	Di-substituted 1,4-piperidine esters and amides having 5-ht4 antagonistic activity
RU2158731C2 (ru)	2000-11-10	Производные ароилпиперидина или их соли, фармацевтический препарат на их основе и способ их получения
JP3833116B2 (ja)	2006-10-11	ビフェニル誘導体、その製法及び薬剤としての使用
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
EP0144986B1 (en)	1987-03-04	Indole-3-carboxamide derivatives
US6197769B1 (en)	2001-03-06	Indazole amide compounds as serotoninergic agents
CZ282919B6 (cs)	1997-11-12	Nové N-alkylenpiperidinové sloučeniny a jejich enantiomery, způsob jejich přípravy a farmaceutické prostředky, které je obsahují
EP0726898B1 (en)	2000-12-20	Phenylindole compounds
US5519025A (en)	1996-05-21	4-indolylpiperazinyl derivatives
PT88543B (pt)	1992-11-30	Processo para a preparacao de compostos derivados de amidina
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