UA71591C2 - 4-(aminomethyl)piperidine benzamide derivatives, pharmaceutical composition based thereon, a process for preparing thereof (variants), an intermediary compound and a method for preparing thereof - Google Patents

4-(aminomethyl)piperidine benzamide derivatives, pharmaceutical composition based thereon, a process for preparing thereof (variants), an intermediary compound and a method for preparing thereof Download PDF

Info

Publication number: UA71591C2
Authority: UA; Ukraine
Prior art keywords: formula; alkyl; compound; group; hydrogen
Prior art date: 1998-12-22

Application number

UA2001064399A

Other languages

English (en)

Ukrainian (uk)

Inventor

Jean-Paul Rene Mari An Bosmans

Klein Michel Anna Joseph De

Henrikus Jacobus Maria Guisen

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.)

1998-12-22

Filing date

1999-12-14

Publication date

2004-12-15

1999-12-14 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2004-12-15 Publication of UA71591C2 publication Critical patent/UA71591C2/uk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 242
238000000034 method Methods 0.000 title claims abstract description 25
239000008194 pharmaceutical composition Substances 0.000 title claims description 7
238000004519 manufacturing process Methods 0.000 title description 5
SZVHQUMEPYZZTA-UHFFFAOYSA-N benzamide;piperidin-4-ylmethanamine Chemical class NCC1CCNCC1.NC(=O)C1=CC=CC=C1 SZVHQUMEPYZZTA-UHFFFAOYSA-N 0.000 title 1
239000001257 hydrogen Substances 0.000 claims abstract description 64
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 64
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 39
150000003839 salts Chemical class 0.000 claims abstract description 34
239000002253 acid Substances 0.000 claims abstract description 24
150000002431 hydrogen Chemical group 0.000 claims abstract description 24
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 20
125000003386 piperidinyl group Chemical group 0.000 claims abstract description 20
125000003118 aryl group Chemical group 0.000 claims abstract description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 10
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
125000004193 piperazinyl group Chemical group 0.000 claims abstract description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 46
238000006243 chemical reaction Methods 0.000 claims description 42
239000011541 reaction mixture Substances 0.000 claims description 39
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 29
150000004820 halides Chemical class 0.000 claims description 28
125000003277 amino group Chemical group 0.000 claims description 25
125000006239 protecting group Chemical group 0.000 claims description 20
125000001424 substituent group Chemical group 0.000 claims description 20
239000003054 catalyst Substances 0.000 claims description 17
239000002585 base Substances 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 8
239000012634 fragment 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
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 6
239000012458 free base Substances 0.000 claims description 6
239000012442 inert solvent Substances 0.000 claims description 6
229910052740 iodine Inorganic materials 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
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
238000005804 alkylation reaction Methods 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
229940002612 prodrug Drugs 0.000 claims description 5
239000000651 prodrug Substances 0.000 claims description 5
238000010992 reflux Methods 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
238000009835 boiling Methods 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
229940126601 medicinal product Drugs 0.000 claims description 2
150000003512 tertiary amines Chemical class 0.000 claims description 2
BQNIFTLCQBTDOH-UHFFFAOYSA-N 2-[4-(aminomethyl)piperidin-1-yl]benzamide Chemical class C1CC(CN)CCN1C1=CC=CC=C1C(N)=O BQNIFTLCQBTDOH-UHFFFAOYSA-N 0.000 claims 3
240000008415 Lactuca sativa Species 0.000 claims 1
150000001299 aldehydes Chemical class 0.000 claims 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
229910052736 halogen Inorganic materials 0.000 claims 1
150000002367 halogens Chemical class 0.000 claims 1
150000002576 ketones Chemical class 0.000 claims 1
235000012045 salad Nutrition 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 77
-1 oxoC5-6cycloalkyl Chemical group 0.000 abstract description 49
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 13
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 6
239000003814 drug Substances 0.000 abstract description 5
229910052760 oxygen Inorganic materials 0.000 abstract description 3
208000018522 Gastrointestinal disease Diseases 0.000 abstract description 2
238000009472 formulation Methods 0.000 abstract description 2
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 abstract 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 abstract 1
125000000815 N-oxide group Chemical group 0.000 abstract 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract 1
229910052717 sulfur Inorganic materials 0.000 abstract 1
RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 abstract 1
239000000543 intermediate Substances 0.000 description 150
239000002904 solvent Substances 0.000 description 57
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
150000003254 radicals Chemical class 0.000 description 34
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 25
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
239000003480 eluent Substances 0.000 description 22
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
238000004587 chromatography analysis Methods 0.000 description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
108010037444 diisopropylglutathione ester Proteins 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 12
239000002244 precipitate Substances 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
239000002552 dosage form Substances 0.000 description 8
238000005984 hydrogenation reaction Methods 0.000 description 8
239000007788 liquid Substances 0.000 description 8
239000000796 flavoring agent Substances 0.000 description 7
238000002347 injection Methods 0.000 description 7
239000007924 injection Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
230000002159 abnormal effect Effects 0.000 description 6
229910000085 borane Inorganic materials 0.000 description 6
201000006549 dyspepsia Diseases 0.000 description 6
235000019441 ethanol Nutrition 0.000 description 6
235000003599 food sweetener Nutrition 0.000 description 6
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
230000035945 sensitivity Effects 0.000 description 6
239000003765 sweetening agent Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
230000009286 beneficial effect Effects 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
239000002775 capsule Substances 0.000 description 5
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 5
235000013355 food flavoring agent Nutrition 0.000 description 5
239000000047 product Substances 0.000 description 5
239000012279 sodium borohydride Substances 0.000 description 5
229910000033 sodium borohydride Inorganic materials 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
241000396377 Tranes Species 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000003042 antagnostic effect Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
235000019634 flavors Nutrition 0.000 description 4
230000002496 gastric effect Effects 0.000 description 4
230000007661 gastrointestinal function Effects 0.000 description 4
239000011521 glass Substances 0.000 description 4
208000024798 heartburn Diseases 0.000 description 4
230000000968 intestinal effect Effects 0.000 description 4
208000002551 irritable bowel syndrome Diseases 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000843 powder Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
238000003786 synthesis reaction Methods 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
206010010774 Constipation Diseases 0.000 description 3
206010012735 Diarrhoea Diseases 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
206010017943 Gastrointestinal conditions Diseases 0.000 description 3
206010020651 Hyperkinesia Diseases 0.000 description 3
208000000269 Hyperkinesis Diseases 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
208000002193 Pain Diseases 0.000 description 3
241000700159 Rattus Species 0.000 description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
238000005810 carbonylation reaction Methods 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
210000001035 gastrointestinal tract Anatomy 0.000 description 3
235000012907 honey Nutrition 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229910052759 nickel Inorganic materials 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
229940081974 saccharin Drugs 0.000 description 3
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
239000006188 syrup Substances 0.000 description 3
KWEISZMWJPDOFR-UHFFFAOYSA-N (1-benzyl-3,6-dihydro-2h-pyridin-4-yl)methanol Chemical compound C1CC(CO)=CCN1CC1=CC=CC=C1 KWEISZMWJPDOFR-UHFFFAOYSA-N 0.000 description 2
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-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
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
241000566113 Branta sandvicensis Species 0.000 description 2
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 2
206010015137 Eructation Diseases 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
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 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000000654 additive Substances 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
239000008365 aqueous carrier Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
208000027687 belching Diseases 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 2
239000000292 calcium oxide Substances 0.000 description 2
ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 2
229940008406 diethyl sulfate Drugs 0.000 description 2
125000000532 dioxanyl group Chemical group 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
235000013305 food Nutrition 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
LFKYBJLFJOOKAE-UHFFFAOYSA-N imidazol-2-ylidenemethanone Chemical class O=C=C1N=CC=N1 LFKYBJLFJOOKAE-UHFFFAOYSA-N 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
239000007927 intramuscular injection Substances 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
238000002156 mixing Methods 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000006187 pill Substances 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
235000019204 saccharin Nutrition 0.000 description 2
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000012453 solvate Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
150000003527 tetrahydropyrans Chemical group 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
229930192474 thiophene Natural products 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
BKBGHCZQGKJRNK-UHFFFAOYSA-N (1-benzyl-2-chloro-2h-pyridin-4-yl)methanol Chemical compound C1=CC(CO)=CC(Cl)N1CC1=CC=CC=C1 BKBGHCZQGKJRNK-UHFFFAOYSA-N 0.000 description 1
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
COQKGJIYPZVMSJ-WDSKDSINSA-N (3r,4s)-4-(hydroxymethyl)piperidin-3-ol Chemical compound OC[C@@H]1CCNC[C@@H]1O COQKGJIYPZVMSJ-WDSKDSINSA-N 0.000 description 1
UOKINRKWPYVMSZ-LADGPHEKSA-N (5r,11as)-2-benzyl-5-(3-hydroxyphenyl)-6h-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carboline-1,3-dione Chemical compound OC1=CC=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H]3N2C(N(CC=2C=CC=CC=2)C3=O)=O)=C1 UOKINRKWPYVMSZ-LADGPHEKSA-N 0.000 description 1
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-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
XDHJBIYJRNFDKS-IBGZPJMESA-N 1-[(4-methoxyphenyl)methyl]-5-[(2s)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione Chemical compound C1=CC(OC)=CC=C1CN1C2=CC=C(S(=O)(=O)N3[C@@H](CCC3)COC=3C=NC=CC=3)C=C2C(=O)C1=O XDHJBIYJRNFDKS-IBGZPJMESA-N 0.000 description 1
BQLHMMQUVJCTAN-UHFFFAOYSA-N 1-chloro-3-methoxypropane Chemical compound COCCCCl BQLHMMQUVJCTAN-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
YNCPXBIZAPNQIJ-UHFFFAOYSA-N 1h-imidazole;sodium Chemical compound [Na].C1=CNC=N1 YNCPXBIZAPNQIJ-UHFFFAOYSA-N 0.000 description 1
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
229940082044 2,3-dihydroxybenzoic acid Drugs 0.000 description 1
CKIIJIDEWWXQEA-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dioxolane Chemical compound BrCC1OCCO1 CKIIJIDEWWXQEA-UHFFFAOYSA-N 0.000 description 1
KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
WZHWPZQQPWKEAV-UHFFFAOYSA-N 2-chloro-3-methylpyrazine Chemical compound CC1=NC=CN=C1Cl WZHWPZQQPWKEAV-UHFFFAOYSA-N 0.000 description 1
BDXYNMVQMBCTDB-UHFFFAOYSA-N 2-chloro-4-methoxypyrimidine Chemical compound COC1=CC=NC(Cl)=N1 BDXYNMVQMBCTDB-UHFFFAOYSA-N 0.000 description 1
MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
UYHSQVMHSFXUOA-UHFFFAOYSA-N 2-methylthiouracil Chemical compound CSC1=NC=CC(O)=N1 UYHSQVMHSFXUOA-UHFFFAOYSA-N 0.000 description 1
DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
MZSAMHOCTRNOIZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylaniline Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(NC2=CC=CC=C2)C=CC=1 MZSAMHOCTRNOIZ-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
ZRXHLJNBNWVNIM-UHFFFAOYSA-N 3-methyl-1-benzofuran Chemical compound C1=CC=C2C(C)=COC2=C1 ZRXHLJNBNWVNIM-UHFFFAOYSA-N 0.000 description 1
CLZQNNVZKPINPC-UHFFFAOYSA-N 4-(aminomethyl)-1-(1,3-dioxolan-2-ylmethyl)piperidin-4-ol Chemical compound C1CC(CN)(O)CCN1CC1OCCO1 CLZQNNVZKPINPC-UHFFFAOYSA-N 0.000 description 1
SGPAPRPKRANLEF-UHFFFAOYSA-N 5-chloro-2,3-dihydro-1-benzofuran-7-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CC2=C1OCC2 SGPAPRPKRANLEF-UHFFFAOYSA-N 0.000 description 1
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
JMIKCDZBVNZHGZ-UHFFFAOYSA-N 7-chloro-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(Cl)C=C2C(=O)O JMIKCDZBVNZHGZ-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
208000002874 Acne Vulgaris Diseases 0.000 description 1
NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
208000010470 Ageusia Diseases 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
241001124076 Aphididae Species 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
108010011485 Aspartame Proteins 0.000 description 1
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
241000167854 Bourreria succulenta Species 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
101100317041 Caenorhabditis elegans vit-1 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
229920002261 Corn starch Polymers 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
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
241000792859 Enema Species 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
235000016623 Fragaria vesca Nutrition 0.000 description 1
240000009088 Fragaria x ananassa Species 0.000 description 1
235000011363 Fragaria x ananassa Nutrition 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000234295 Musa Species 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
241000277269 Oncorhynchus masou Species 0.000 description 1
241001079606 Paches Species 0.000 description 1
241000282320 Panthera leo Species 0.000 description 1
101000579646 Penaeus vannamei Penaeidin-1 Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
101100209990 Rattus norvegicus Slc18a2 gene Proteins 0.000 description 1
240000001890 Ribes hudsonianum Species 0.000 description 1
235000016954 Ribes hudsonianum Nutrition 0.000 description 1
235000001466 Ribes nigrum Nutrition 0.000 description 1
235000011034 Rubus glaucus Nutrition 0.000 description 1
244000235659 Rubus idaeus Species 0.000 description 1
235000009122 Rubus idaeus Nutrition 0.000 description 1
102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 1
108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 1
241001538551 Sibon Species 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
239000004376 Sucralose Substances 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
241001424341 Tara spinosa Species 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
206010047700 Vomiting Diseases 0.000 description 1
238000007239 Wittig reaction Methods 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
SAHIZENKTPRYSN-UHFFFAOYSA-N [2-[3-(phenoxymethyl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)CC=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 SAHIZENKTPRYSN-UHFFFAOYSA-N 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
235000010358 acesulfame potassium Nutrition 0.000 description 1
229960004998 acesulfame potassium Drugs 0.000 description 1
239000000619 acesulfame-K Substances 0.000 description 1
206010000496 acne Diseases 0.000 description 1
235000019666 ageusia Nutrition 0.000 description 1
238000013019 agitation Methods 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001447 alkali salts Chemical group 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000008485 antagonism Effects 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000036528 appetite Effects 0.000 description 1
235000019789 appetite Nutrition 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
125000005002 aryl methyl group Chemical group 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
239000012752 auxiliary agent Substances 0.000 description 1
IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
235000013405 beer Nutrition 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
230000036983 biotransformation Effects 0.000 description 1
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical class [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
239000012267 brine Substances 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 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
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
230000006315 carbonylation Effects 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
230000002026 carminative effect Effects 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
235000019693 cherries Nutrition 0.000 description 1
230000001055 chewing effect Effects 0.000 description 1
238000010568 chiral column chromatography Methods 0.000 description 1
239000003245 coal Substances 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
229940125797 compound 12 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
239000012059 conventional drug carrier Substances 0.000 description 1
239000010949 copper Substances 0.000 description 1
JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229940109275 cyclamate Drugs 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
150000002012 dioxanes Chemical group 0.000 description 1
AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
230000001667 episodic effect Effects 0.000 description 1
210000003238 esophagus Anatomy 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
SPTSCZKKNIZEKX-VHSXEESVSA-N ethyl (3s,4s)-4-(aminomethyl)-3-ethoxypiperidine-1-carboxylate Chemical compound CCO[C@@H]1CN(C(=O)OCC)CC[C@H]1CN SPTSCZKKNIZEKX-VHSXEESVSA-N 0.000 description 1
MGPVWYRXVHWIIE-VHSXEESVSA-N ethyl (3s,4s)-4-cyano-3-ethoxypiperidine-1-carboxylate Chemical compound CCO[C@@H]1CN(C(=O)OCC)CC[C@H]1C#N MGPVWYRXVHWIIE-VHSXEESVSA-N 0.000 description 1
GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
MEHDPHFVOFBZMT-UHFFFAOYSA-N ethyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(O)(CN)CC1 MEHDPHFVOFBZMT-UHFFFAOYSA-N 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
229960004038 fluvoxamine Drugs 0.000 description 1
235000010855 food raising agent Nutrition 0.000 description 1
239000008369 fruit flavor Substances 0.000 description 1
230000006870 function Effects 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
239000000499 gel Substances 0.000 description 1
150000002303 glucose derivatives Chemical class 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
230000009931 harmful effect Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000006038 hexenyl group Chemical group 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
238000004128 high performance liquid chromatography Methods 0.000 description 1
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical class C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000002513 implantation Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 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
239000007951 isotonicity adjuster Substances 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
125000000468 ketone group Chemical group 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
NWLWOSLKONPRKX-UHFFFAOYSA-N methyl 5-chloro-2,3-dihydroxybenzoate Chemical compound COC(=O)C1=CC(Cl)=CC(O)=C1O NWLWOSLKONPRKX-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
230000008693 nausea Effects 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
230000000422 nocturnal effect Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
210000004197 pelvis Anatomy 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000008855 peristalsis Effects 0.000 description 1
230000035699 permeability Effects 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000002028 premature Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
JADFCQKRKICRKI-UHFFFAOYSA-N quinoline;sulfane Chemical compound S.N1=CC=CC2=CC=CC=C21 JADFCQKRKICRKI-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000000452 restraining effect Effects 0.000 description 1
229940085605 saccharin sodium Drugs 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000013049 sediment Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
229940083037 simethicone Drugs 0.000 description 1
239000000779 smoke Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
229940013618 stevioside Drugs 0.000 description 1
OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
235000019202 steviosides Nutrition 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
235000019408 sucralose Nutrition 0.000 description 1
BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
230000009747 swallowing Effects 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
GAGALXYDHSHHCD-RKDXNWHRSA-N tert-butyl (3s,4r)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](CN)[C@H](O)C1 GAGALXYDHSHHCD-RKDXNWHRSA-N 0.000 description 1
GAGALXYDHSHHCD-DTWKUNHWSA-N tert-butyl (3s,4s)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](CN)[C@H](O)C1 GAGALXYDHSHHCD-DTWKUNHWSA-N 0.000 description 1
AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 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
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical class C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 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
235000012431 wafers Nutrition 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)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (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)

UA2001064399A 1998-12-22 1999-12-14 4-(aminomethyl)piperidine benzamide derivatives, pharmaceutical composition based thereon, a process for preparing thereof (variants), an intermediary compound and a method for preparing thereof UA71591C2 (en)

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
UA71591C2 true UA71591C2 (en)	2004-12-15

Family

ID=8234539

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2001064399A UA71591C2 (en)	1998-12-22	1999-12-14	4-(aminomethyl)piperidine benzamide derivatives, pharmaceutical composition based thereon, a process for preparing thereof (variants), an intermediary compound and a method for preparing thereof

Country Status (34)

Country	Link
US (2)	US6544997B1 (hr)
EP (1)	EP1140915B1 (hr)
JP (1)	JP4615725B2 (hr)
KR (1)	KR100633680B1 (hr)
CN (1)	CN1150190C (hr)
AR (1)	AR024240A1 (hr)
AT (1)	ATE297917T1 (hr)
AU (1)	AU770397B2 (hr)
BG (1)	BG64953B1 (hr)
BR (1)	BR9916491A (hr)
CA (1)	CA2355857C (hr)
CZ (1)	CZ300851B6 (hr)
DE (1)	DE69925865T2 (hr)
DK (1)	DK1140915T3 (hr)
EA (1)	EA003608B1 (hr)
EE (1)	EE200100335A (hr)
ES (1)	ES2245131T3 (hr)
HK (1)	HK1039114B (hr)
HR (1)	HRP20010445A2 (hr)
HU (1)	HUP0104838A3 (hr)
ID (1)	ID28953A (hr)
IL (1)	IL143858A (hr)
MY (1)	MY121852A (hr)
NO (1)	NO321324B1 (hr)
NZ (1)	NZ512871A (hr)
PL (1)	PL197409B1 (hr)
PT (1)	PT1140915E (hr)
SI (1)	SI1140915T1 (hr)
SK (1)	SK285829B6 (hr)
TR (1)	TR200101962T2 (hr)
TW (1)	TW570920B (hr)
UA (1)	UA71591C2 (hr)
WO (1)	WO2000037461A1 (hr)
ZA (1)	ZA200105135B (hr)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2002335161A1 (en) *	2002-09-12	2004-04-30	Nagase Chemtex Corporation	Medicinal composition
JO2478B1 (en)	2003-06-19	2009-01-20	جانسين فارماسوتيكا ان. في.	(Aminomethyl) -biperidine benzamides as 5 HT4 antagonists
CA2526079C (en) *	2003-06-19	2012-01-10	Janssen Pharmaceutica N.V.	Aminosulfonyl substituted 4-(aminomethyl)-piperidine benzamides as 5ht4-antagonists
ES2355824T3 (es) *	2003-06-19	2011-03-31	Janssen Pharmaceutica Nv	4-(aminometil)-piperidina-benzamidas sustituidas con hidroxicarbonilfenilo como antagonistas 5ht4.
CA2528642C (en)	2003-06-19	2011-12-13	Janssen Pharmaceutica N.V.	Heterocyclic substituted 4-(aminomethyl)-piperidine benzamides as 5ht4-antagonists
WO2005003122A1 (en) *	2003-06-19	2005-01-13	Janssen Pharmaceutica N.V.	5ht4-antagonistic 4-(aminomethyl)-piperidine benzamides
OA13248A (en) *	2003-09-03	2007-01-31	Pfizer	Benzimidazolone coumpounds having 5-HT4 receptor agonistic activity.
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
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
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
ATE431824T1 (de) *	2004-11-05	2009-06-15	Theravance Inc	Chinolinon-carboxamid-verbindungen
DE602005016446D1 (de) *	2004-11-05	2009-10-15	Theravance Inc	5-HT4-Rezeptoragonistenverbindungen
AU2005319190A1 (en) *	2004-12-22	2006-06-29	Theravance, Inc.	Indazole-carboxamide compounds
AU2006218603A1 (en) *	2005-03-02	2006-09-08	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
WO2014134306A1 (en)	2013-03-01	2014-09-04	Zalicus Pharmaceuticals, Ltd.	Heterocyclic inhibitors of the sodium channel
US20180305334A1 (en) *	2015-10-14	2018-10-25	Aquinnah Pharmaceuticals, Inc.	Compounds, compositions and methods of use against stress granules
WO2021007487A1 (en)	2019-07-11	2021-01-14	Praxis Precision Medicines, Inc.	Formulations of t-type calcium channel modulators and methods of use thereof

Family Cites Families (21)

* Cited by examiner, † Cited by third party
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
WO1993003725A1 (en)	1991-08-20	1993-03-04	Smithkline Beecham Plc	5-ht4 receptor antagonists
ATE182591T1 (de) *	1991-09-12	1999-08-15	Smithkline Beecham Plc	5-ht4 rezeptor antagonisten
ATE172201T1 (de) *	1992-01-23	1998-10-15	Toray Industries	Morphinan-derivate und medizinische verwendung
NZ246915A (en)	1992-02-06	1996-05-28	Smithkline Beecham Plc	Benzopyran, benzothiopyran and benzofuran derivatives, preparation and pharmaceutical compositions thereof
GB9219163D0 (en)	1992-09-10	1992-10-28	Smithkline Beecham Plc	Pharmaceuticals
AU5150393A (en)	1992-10-13	1994-05-09	Smithkline Beecham Plc	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
JPH08502741A (ja)	1992-11-05	1996-03-26	スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー	５−ｈｔ▲下４▼レセプターアンタゴニスト用のピペリジン誘導体
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
TW548103B (en) *	1997-07-11	2003-08-21	Janssen Pharmaceutica Nv	Bicyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives
KR100413150B1 (ko) *	1998-09-10	2003-12-31	에프. 호프만-라 로슈 아게	5-에이치티4 수용체 길항제로서의 디하이드로벤조디옥신 카복스아미드 및 케톤 유도체
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 EA EA200100710A patent/EA003608B1/ru not_active IP Right Cessation
- 1999-12-14 JP JP2000589532A patent/JP4615725B2/ja not_active Expired - Fee Related
- 1999-12-14 WO PCT/EP1999/010064 patent/WO2000037461A1/en active IP Right Grant
- 1999-12-14 HU HU0104838A patent/HUP0104838A3/hu unknown
- 1999-12-14 CN CNB998147699A patent/CN1150190C/zh not_active Expired - Fee Related
- 1999-12-14 ES ES99967956T patent/ES2245131T3/es not_active Expired - Lifetime
- 1999-12-14 PT PT99967956T patent/PT1140915E/pt unknown
- 1999-12-14 TR TR2001/01962T patent/TR200101962T2/xx unknown
- 1999-12-14 AT AT99967956T patent/ATE297917T1/de not_active IP Right Cessation
- 1999-12-14 ID IDW00200101336A patent/ID28953A/id unknown
- 1999-12-14 PL PL348417A patent/PL197409B1/pl unknown
- 1999-12-14 KR KR1020017005055A patent/KR100633680B1/ko not_active IP Right Cessation
- 1999-12-14 IL IL14385899A patent/IL143858A/xx not_active IP Right Cessation
- 1999-12-14 EP EP99967956A patent/EP1140915B1/en not_active Expired - Lifetime
- 1999-12-14 SK SK859-2001A patent/SK285829B6/sk not_active IP Right Cessation
- 1999-12-14 DE DE69925865T patent/DE69925865T2/de not_active Expired - Lifetime
- 1999-12-14 SI SI9930822T patent/SI1140915T1/sl unknown
- 1999-12-14 NZ NZ512871A patent/NZ512871A/xx unknown
- 1999-12-14 CZ CZ20012117A patent/CZ300851B6/cs not_active IP Right Cessation
- 1999-12-14 US US09/857,905 patent/US6544997B1/en not_active Expired - Lifetime
- 1999-12-14 DK DK99967956T patent/DK1140915T3/da active
- 1999-12-14 UA UA2001064399A patent/UA71591C2/uk unknown
- 1999-12-14 BR BR9916491-4A patent/BR9916491A/pt not_active Application Discontinuation
- 1999-12-14 AU AU24328/00A patent/AU770397B2/en not_active Ceased
- 1999-12-14 EE EEP200100335A patent/EE200100335A/xx unknown
- 1999-12-14 CA CA002355857A patent/CA2355857C/en not_active Expired - Fee Related
- 1999-12-17 MY MYPI99005534A patent/MY121852A/en unknown
- 1999-12-21 AR ARP990106644A patent/AR024240A1/es active IP Right Grant
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
2002
- 2002-01-29 HK HK02100161.1A patent/HK1039114B/zh not_active IP Right Cessation
2003
- 2003-01-29 US US10/353,307 patent/US7205410B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
HK1039114B (zh)	2005-08-19
EP1140915B1 (en)	2005-06-15
US6544997B1 (en)	2003-04-08
AU2432800A (en)	2000-07-12
SK8592001A3 (en)	2002-02-05
DK1140915T3 (da)	2005-10-10
HK1039114A1 (en)	2002-04-12
IL143858A0 (en)	2002-04-21
EA200100710A1 (ru)	2001-12-24
CA2355857A1 (en)	2000-06-29
NZ512871A (en)	2002-11-26
MY121852A (en)	2006-02-28
CA2355857C (en)	2008-10-28
DE69925865D1 (de)	2005-07-21
BG105571A (en)	2002-01-31
KR20010080293A (ko)	2001-08-22
KR100633680B1 (ko)	2006-10-11
NO321324B1 (no)	2006-04-24
PT1140915E (pt)	2005-11-30
CZ300851B6 (cs)	2009-08-26
ID28953A (id)	2001-07-19
PL348417A1 (en)	2002-05-20
CN1331690A (zh)	2002-01-16
EA003608B1 (ru)	2003-06-26
AU770397B2 (en)	2004-02-19
TW570920B (en)	2004-01-11
WO2000037461A1 (en)	2000-06-29
CZ20012117A3 (cs)	2001-10-17
TR200101962T2 (tr)	2002-04-22
NO20012858L (no)	2001-06-08
HRP20010445A2 (en)	2002-06-30
ATE297917T1 (de)	2005-07-15
IL143858A (en)	2005-03-20
BR9916491A (pt)	2001-09-04
HUP0104838A3 (en)	2003-05-28
JP4615725B2 (ja)	2011-01-19
PL197409B1 (pl)	2008-03-31
AR024240A1 (es)	2002-09-25
ES2245131T3 (es)	2005-12-16
EE200100335A (et)	2002-08-15
CN1150190C (zh)	2004-05-19
NO20012858D0 (no)	2001-06-08
DE69925865T2 (de)	2006-05-11
SK285829B6 (sk)	2007-09-06
EP1140915A1 (en)	2001-10-10
SI1140915T1 (sl)	2005-12-31
HUP0104838A2 (hu)	2002-07-29
ZA200105135B (en)	2002-06-21
US20030181456A1 (en)	2003-09-25
BG64953B1 (bg)	2006-10-31
US7205410B2 (en)	2007-04-17
JP2002533337A (ja)	2002-10-08

Publication	Publication Date	Title
UA71591C2 (en)	2004-12-15	4-(aminomethyl)piperidine benzamide derivatives, pharmaceutical composition based thereon, a process for preparing thereof (variants), an intermediary compound and a method for preparing thereof
DE69820065T2 (de)	2004-08-26	Gastrokinetische monocyclische benzamide von 3- oder 4-substituierte 4-(aminomethyl)-piperidinderivative
AU2006332124B2 (en)	2011-03-03	3 , 5-substitgammaued piperidine compounds as renin inhibitors
CA2979504C (en)	2023-10-10	Benzimidazole derivatives as bromodomain inhibitors
NZ332777A (en)	2000-06-23	3,6-bi-phenyl substituted spiro-piperidine derivatives
JP5805792B2 (ja)	2015-11-10	ヒスタミンｈ３レセプターリガンドとしての新規な化合物
NO339158B1 (no)	2016-11-14	Salt av arylamidin-derivat og anti-soppmiddel inneholdende dette
US7091354B2 (en)	2006-08-15	Processes for the preparation of peripheral opioid antagonist compounds and intermediates thereto
AU2012302723A1 (en)	2014-02-27	Pyrazole compound and use thereof for medical purposes
WO2003014113A1 (en)	2003-02-20	Novel benzopyran compounds and process for their preparation and use
DE69513846T2 (de)	2000-07-06	N-substituierte piperidinyl bicyclische benzoatderivate
US4420485A (en)	1983-12-13	1'-[3-(1,2-Benzisoxazol-3-yl) proply]spiro[benzofuran-2(3H),3' or 4'-piperidines or 3'-pyrrolidines]
EA009259B1 (ru)	2007-12-28	Аминосульфонилзамещенные 4-(аминометил)пиперидинбензамиды в качестве 5ht-антагонистов
EA010312B1 (ru)	2008-08-29	Замещенные производные 4-алкил- и 4-алканоилпиперидина и их применение в качестве антагонистов нейрокининов
ES2355580T3 (es)	2011-03-29	Derivados de 2-oxoimidazol sustituidos con n-dihidroxialquilo.
EP0449195A2 (en)	1991-10-02	Aminobenzene compounds, their production and use
KR20060009313A (ko)	2006-01-31	시클릭 아민 유도체, 이들의 제조 방법, 및 이들을함유하는 제약 조성물
WO1996030372A1 (fr)	1996-10-03	Derives diazabicyclo[3.3.1]nonane et leurs intermediaires, leur application therapeutique et procedes de production
IL124321A (en)	2004-01-04	Esters of the history of 3-hydroxy-piperidinemethanol, intermediates and process for their preparation and pharmaceutical preparations containing them
JPS6360958A (ja)	1988-03-17	非イオン造影剤合成用中間体
EA009464B1 (ru)	2007-12-28	Бензамиды 4-(аминометил)пиперидина, замещённого гидроксикарбонилфенилом, в качестве антагонистов 5нт-рецепторов
MXPA00000418A (en)	2001-11-21	Gastrokinetic monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives
NZ622539B2 (en)	2015-09-01	Diphenoxyphenyl derivative
MXPA01006409A (en)	2001-12-13	4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders