HRP20010445A2 - 4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders - Google Patents
4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders Download PDFInfo
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- HRP20010445A2 HRP20010445A2 HR20010445A HRP20010445A HRP20010445A2 HR P20010445 A2 HRP20010445 A2 HR P20010445A2 HR 20010445 A HR20010445 A HR 20010445A HR P20010445 A HRP20010445 A HR P20010445A HR P20010445 A2 HRP20010445 A2 HR P20010445A2
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- Prior art keywords
- formula
- alkyl
- hydroxy
- hydrogen
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- 208000018522 Gastrointestinal disease Diseases 0.000 title description 2
- SZVHQUMEPYZZTA-UHFFFAOYSA-N benzamide;piperidin-4-ylmethanamine Chemical class NCC1CCNCC1.NC(=O)C1=CC=CC=C1 SZVHQUMEPYZZTA-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 103
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 62
- -1 oxo-C5-6-cycloalkyl Chemical group 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 46
- 239000011541 reaction mixture Substances 0.000 claims description 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000003386 piperidinyl group Chemical group 0.000 claims description 19
- 150000002431 hydrogen Chemical group 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 239000002585 base Substances 0.000 claims description 14
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 8
- 150000001204 N-oxides Chemical class 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 239000012442 inert solvent Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000000651 prodrug Substances 0.000 claims description 6
- 229940002612 prodrug Drugs 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- 150000002012 dioxanes Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 3
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 3
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 3
- 229910005965 SO 2 Inorganic materials 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 144
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 97
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 64
- 239000000203 mixture Substances 0.000 description 63
- 239000002904 solvent Substances 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 38
- 150000003254 radicals Chemical class 0.000 description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 239000003480 eluent Substances 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 18
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 238000002844 melting Methods 0.000 description 14
- 230000008018 melting Effects 0.000 description 14
- 208000002551 irritable bowel syndrome Diseases 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000002496 gastric effect Effects 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 206010020751 Hypersensitivity Diseases 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 208000026935 allergic disease Diseases 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
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- 201000006549 dyspepsia Diseases 0.000 description 6
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- 230000009610 hypersensitivity Effects 0.000 description 6
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- 235000013599 spices Nutrition 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 5
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- 230000000694 effects Effects 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
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- 239000003921 oil Substances 0.000 description 5
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- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
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- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
- 238000007126 N-alkylation reaction Methods 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
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- 239000003523 serotonin 4 antagonist Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 3
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- LBHRCDXREMLNCV-MELYUZJYSA-N tert-butyl (3s,4s)-4-[[(8-chloro-3,4-dihydro-2h-1,5-benzodioxepine-6-carbonyl)amino]methyl]-3-hydroxypiperidine-1-carboxylate;hydrate Chemical compound O.O[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1CNC(=O)C1=CC(Cl)=CC2=C1OCCCO2 LBHRCDXREMLNCV-MELYUZJYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- MDDPTCUZZASZIQ-UHFFFAOYSA-N tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] MDDPTCUZZASZIQ-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Otolaryngology (AREA)
- Hospice & Palliative Care (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98204411 | 1998-12-22 | ||
| PCT/EP1999/010064 WO2000037461A1 (en) | 1998-12-22 | 1999-12-14 | 4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20010445A2 true HRP20010445A2 (en) | 2002-06-30 |
Family
ID=8234539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20010445A HRP20010445A2 (en) | 1998-12-22 | 2001-06-14 | 4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders |
Country Status (34)
| Country | Link |
|---|---|
| US (2) | US6544997B1 (es) |
| EP (1) | EP1140915B1 (es) |
| JP (1) | JP4615725B2 (es) |
| KR (1) | KR100633680B1 (es) |
| CN (1) | CN1150190C (es) |
| AR (1) | AR024240A1 (es) |
| AT (1) | ATE297917T1 (es) |
| AU (1) | AU770397B2 (es) |
| BG (1) | BG64953B1 (es) |
| BR (1) | BR9916491A (es) |
| CA (1) | CA2355857C (es) |
| CZ (1) | CZ300851B6 (es) |
| DE (1) | DE69925865T2 (es) |
| DK (1) | DK1140915T3 (es) |
| EA (1) | EA003608B1 (es) |
| EE (1) | EE200100335A (es) |
| ES (1) | ES2245131T3 (es) |
| HK (1) | HK1039114B (es) |
| HR (1) | HRP20010445A2 (es) |
| HU (1) | HUP0104838A3 (es) |
| ID (1) | ID28953A (es) |
| IL (1) | IL143858A (es) |
| MY (1) | MY121852A (es) |
| NO (1) | NO321324B1 (es) |
| NZ (1) | NZ512871A (es) |
| PL (1) | PL197409B1 (es) |
| PT (1) | PT1140915E (es) |
| SI (1) | SI1140915T1 (es) |
| SK (1) | SK285829B6 (es) |
| TR (1) | TR200101962T2 (es) |
| TW (1) | TW570920B (es) |
| UA (1) | UA71591C2 (es) |
| WO (1) | WO2000037461A1 (es) |
| ZA (1) | ZA200105135B (es) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7485665B2 (en) * | 2002-09-12 | 2009-02-03 | Nagase Chemtex Corporation | Medicinal composition |
| JO2478B1 (en) * | 2003-06-19 | 2009-01-20 | جانسين فارماسوتيكا ان. في. | (Aminomethyl) -biperidine benzamides as 5 HT4 antagonists |
| EP1641782B1 (en) * | 2003-06-19 | 2010-11-03 | Janssen Pharmaceutica NV | Hydroxycarbonylphenyl substituted 4-(aminomethyl)-piperidine benzamides as 5ht4-antagonists |
| CA2526079C (en) * | 2003-06-19 | 2012-01-10 | Janssen Pharmaceutica N.V. | Aminosulfonyl substituted 4-(aminomethyl)-piperidine benzamides as 5ht4-antagonists |
| AU2004254190B2 (en) | 2003-06-19 | 2010-04-22 | Janssen Pharmaceutica N.V. | Heterocyclic substituted 4-(aminomethyl)-piperidine benzamides as 5HT4-antagonists |
| KR20060022702A (ko) | 2003-06-19 | 2006-03-10 | 얀센 파마슈티카 엔.브이. | 5ｈｔ4-길항성 4-(아미노메틸)-피페리딘벤즈아미드 |
| ATE539077T1 (de) * | 2003-09-03 | 2012-01-15 | Pfizer | Benzimidazolonverbindungen mit agonistischer wirkung am 5-ht4 rezeptor |
| BRPI0416813A (pt) * | 2003-11-24 | 2007-03-06 | Pfizer | compostos de ácido quinolonacarboxìlico com atividade agonista do receptor 5-ht4 |
| TW200533348A (en) * | 2004-02-18 | 2005-10-16 | Theravance Inc | Indazole-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 |
| US7728006B2 (en) * | 2004-04-07 | 2010-06-01 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| GEP20094638B (en) | 2004-06-15 | 2009-03-10 | Pfizer | Benzimidazolone carboxylic acid derivatives |
| US20060035890A1 (en) * | 2004-08-10 | 2006-02-16 | Amit Banerjee | Compounds and methods for the treatment of ubiquitin conjugating disorders |
| 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 |
| JP5086091B2 (ja) * | 2004-11-05 | 2012-11-28 | セラヴァンス， インコーポレーテッド | ５−ｈｔ４受容体アゴニスト化合物 |
| BRPI0519708A2 (pt) * | 2004-12-22 | 2009-03-10 | Theravance Inc | compostos de indazol-carboxamida |
| EP1871772B1 (en) * | 2005-03-02 | 2014-09-10 | Theravance, Inc. | Quinolinone compounds as 5-ht4 receptor agonists |
| US9101160B2 (en) | 2005-11-23 | 2015-08-11 | The Coca-Cola Company | Condiments with high-potency sweetener |
| US8017168B2 (en) | 2006-11-02 | 2011-09-13 | The Coca-Cola Company | High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith |
| US8377968B2 (en) | 2008-06-02 | 2013-02-19 | Zalicus Pharmaceuticals, Ltd. | N-piperidinyl acetamide derivatives as calcium channel blockers |
| EP2961403A4 (en) | 2013-03-01 | 2016-11-30 | Zalicus Pharmaceuticals Ltd | HETEROCYCLIC INHIBITORS OF SODIUM CHANNEL |
| WO2017066705A1 (en) * | 2015-10-14 | 2017-04-20 | Aquinnah Pharmaceuticals, Inc. | Compounds, compositions and methods of use against stress granules |
| AU2020311942A1 (en) | 2019-07-11 | 2022-02-24 | Praxis Precision Medicines, Inc. | Formulations of T-type calcium channel modulators and methods of use thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ225152A (en) * | 1987-07-17 | 1990-04-26 | Janssen Pharmaceutica Nv | Heterocyclically substituted piperidinyl benzamides as pharmaceuticals |
| CA1317940C (en) * | 1987-09-25 | 1993-05-18 | Georges H. P. Van Daele | Substituted n-(1-alkyl-3-hydroxy-4-piperidinyl)benzamides |
| 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 |
| CA2116024A1 (en) | 1991-08-20 | 1993-03-04 | Francis David King | 5-ht4 receptor antagonists |
| CZ283619B6 (cs) * | 1991-09-12 | 1998-05-13 | Smithkline Beecham P.L.C | Použití derivátů kyseliny benzoové pro výrobu farmaceutických prostředků, deriváty kyseliny benzoo vé, způsob jejich výroby a farmaceutické prostředky s jejich obsahem |
| DK0577847T3 (da) * | 1992-01-23 | 1999-06-23 | Toray Industries | Morphinanderivat og medicinsk anvendelse deraf |
| EP0625149A1 (en) * | 1992-02-06 | 1994-11-23 | Smithkline Beecham Plc | Benzopyran, benzothiopyran and benzofuran derivatives as 5-ht4 antagonists |
| WO1994008994A1 (en) | 1992-10-13 | 1994-04-28 | Smithkline Beecham Plc | Heterocyclic -esters or -amides used as 5-ht4 receptor antagonists |
| GB9219163D0 (en) | 1992-09-10 | 1992-10-28 | Smithkline Beecham Plc | Pharmaceuticals |
| 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 |
| KR950704328A (ko) * | 1992-11-05 | 1995-11-17 | 데이비드 로버츠 | 5-HT₄ 수용체 길항제로서의 피페리딘 유도체(Piperidine Derivatives as 5-HT₄ Receptor Antagonists) |
| GB9301660D0 (en) | 1993-01-28 | 1993-03-17 | Smithkline Beecham Plc | Pharmaceuticals |
| GB9312348D0 (en) | 1993-06-16 | 1993-07-28 | Smithkline Beecham Plc | Pharmaceuticals |
| ES2103675B1 (es) * | 1995-01-10 | 1998-07-01 | Almirall Lab | Nuevas piperidinas sustituidas. |
| IT1275903B1 (it) | 1995-03-14 | 1997-10-24 | Boehringer Ingelheim Italia | Esteri e ammidi della 1,4-piperidina disostituita |
| GB9507882D0 (en) | 1995-04-18 | 1995-05-31 | Pharmacia Spa | Substituted dihydrobenzofuran derivatives as 5-ht4 agonists |
| AU1767997A (en) * | 1996-02-15 | 1997-09-02 | Janssen Pharmaceutica N.V. | Use of 5ht4 receptor antagonists for overcoming gastrointestinal effects of serotonin reuptake inhibitors |
| TW445263B (en) | 1996-02-29 | 2001-07-11 | Janssen Pharmaceutica Nv | Novel esters of 1,4-disubstituted piperidine derivatives |
| TW402591B (en) * | 1997-07-11 | 2000-08-21 | Janssen Pharmaceutica Nv | Monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives |
| AU758807B2 (en) * | 1998-09-10 | 2003-03-27 | F. Hoffmann-La Roche Ag | Dihydrobenzodioxine carboxamide and ketone derivatives as 5-HT4 receptor antagonists |
| DE10217868A1 (de) * | 2002-04-22 | 2003-10-30 | Jomed N V | Ballon-Katheter |
-
1999
- 1999-12-03 TW TW088121125A patent/TW570920B/zh not_active IP Right Cessation
- 1999-12-14 CA CA002355857A patent/CA2355857C/en not_active Expired - Fee Related
- 1999-12-14 SK SK859-2001A patent/SK285829B6/sk not_active IP Right Cessation
- 1999-12-14 PT PT99967956T patent/PT1140915E/pt unknown
- 1999-12-14 EE EEP200100335A patent/EE200100335A/xx unknown
- 1999-12-14 IL IL14385899A patent/IL143858A/xx not_active IP Right Cessation
- 1999-12-14 EA EA200100710A patent/EA003608B1/ru not_active IP Right Cessation
- 1999-12-14 KR KR1020017005055A patent/KR100633680B1/ko not_active IP Right Cessation
- 1999-12-14 AT AT99967956T patent/ATE297917T1/de not_active IP Right Cessation
- 1999-12-14 JP JP2000589532A patent/JP4615725B2/ja not_active Expired - Fee Related
- 1999-12-14 TR TR2001/01962T patent/TR200101962T2/xx unknown
- 1999-12-14 CZ CZ20012117A patent/CZ300851B6/cs not_active IP Right Cessation
- 1999-12-14 SI SI9930822T patent/SI1140915T1/sl unknown
- 1999-12-14 BR BR9916491-4A patent/BR9916491A/pt not_active Application Discontinuation
- 1999-12-14 CN CNB998147699A patent/CN1150190C/zh not_active Expired - Fee Related
- 1999-12-14 DK DK99967956T patent/DK1140915T3/da active
- 1999-12-14 NZ NZ512871A patent/NZ512871A/xx unknown
- 1999-12-14 ID IDW00200101336A patent/ID28953A/id unknown
- 1999-12-14 PL PL348417A patent/PL197409B1/pl unknown
- 1999-12-14 HU HU0104838A patent/HUP0104838A3/hu unknown
- 1999-12-14 EP EP99967956A patent/EP1140915B1/en not_active Expired - Lifetime
- 1999-12-14 US US09/857,905 patent/US6544997B1/en not_active Expired - Lifetime
- 1999-12-14 WO PCT/EP1999/010064 patent/WO2000037461A1/en active IP Right Grant
- 1999-12-14 DE DE69925865T patent/DE69925865T2/de not_active Expired - Lifetime
- 1999-12-14 UA UA2001064399A patent/UA71591C2/uk unknown
- 1999-12-14 ES ES99967956T patent/ES2245131T3/es not_active Expired - Lifetime
- 1999-12-14 AU AU24328/00A patent/AU770397B2/en not_active Ceased
- 1999-12-17 MY MYPI99005534A patent/MY121852A/en unknown
- 1999-12-21 AR ARP990106644A patent/AR024240A1/es active IP Right Grant
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2001
- 2001-06-07 BG BG105571A patent/BG64953B1/bg unknown
- 2001-06-08 NO NO20012858A patent/NO321324B1/no not_active IP Right Cessation
- 2001-06-14 HR HR20010445A patent/HRP20010445A2/hr not_active Application Discontinuation
- 2001-06-21 ZA ZA200105135A patent/ZA200105135B/en unknown
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2002
- 2002-01-29 HK HK02100161.1A patent/HK1039114B/zh not_active IP Right Cessation
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2003
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Also Published As
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