CA1330081C - Heterocycle bicyclique contenant des n-(heterocycle, bicyclique)-4-piperidinamines - Google Patents

Heterocycle bicyclique contenant des n-(heterocycle, bicyclique)-4-piperidinamines

Info

Publication number: CA1330081C
Authority: CA; Canada
Prior art keywords: parts; methyl; formula; amino; lower alkyl
Prior art date: 1983-11-30
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000564954A

Other languages

English (en)

Inventor

Theophilus Theresia Joannes Maria Van Offenwert

Jozef Francis Hens

Joseph Leo Ghislanus Torremans

Frans Eduard Janssens

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Janssen Pharmaceutica NV

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.)

1983-11-30

Filing date

1988-04-22

Publication date

1994-06-07

1984-10-12 Priority claimed from US06/660,608 external-priority patent/US4695569A/en

1984-11-26 Priority claimed from CA000468587A external-priority patent/CA1257258A/fr

1988-04-22 Application filed by Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV

1988-04-22 Priority to CA000564954A priority Critical patent/CA1330081C/fr

1994-06-07 Application granted granted Critical

1994-06-07 Publication of CA1330081C publication Critical patent/CA1330081C/fr

2011-06-07 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

125000002618 bicyclic heterocycle group Chemical group 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 109
239000003795 chemical substances by application Substances 0.000 claims abstract description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 138
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 71
-1 mercapto, amino Chemical group 0.000 claims description 71
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 69
150000003254 radicals Chemical class 0.000 claims description 51
125000000217 alkyl group Chemical group 0.000 claims description 46
238000000034 method Methods 0.000 claims description 40
229910052739 hydrogen Inorganic materials 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 30
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 27
239000002904 solvent Substances 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 17
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
125000004414 alkyl thio group Chemical group 0.000 claims description 5
239000003960 organic solvent Substances 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
239000011593 sulfur Substances 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
229910044991 metal oxide Inorganic materials 0.000 claims description 4
150000004706 metal oxides Chemical class 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
150000001350 alkyl halides Chemical class 0.000 claims description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 claims description 2
CDEIGFNQWMSEKG-UHFFFAOYSA-M chloro-[4-[(2-hydroxynaphthalen-1-yl)diazenyl]phenyl]mercury Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC1=CC=C([Hg]Cl)C=C1 CDEIGFNQWMSEKG-UHFFFAOYSA-M 0.000 claims description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 2
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 claims description 2
VPKDCDLSJZCGKE-UHFFFAOYSA-N methanediimine Chemical compound N=C=N VPKDCDLSJZCGKE-UHFFFAOYSA-N 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
VNIOQSAWKLOGLY-UHFFFAOYSA-N 3-[(5-methylfuran-2-yl)methyl]-n-piperidin-4-ylimidazo[4,5-b]pyridin-2-amine Chemical compound O1C(C)=CC=C1CN1C2=NC=CC=C2N=C1NC1CCNCC1 VNIOQSAWKLOGLY-UHFFFAOYSA-N 0.000 claims 1
INQOMBQAUSQDDS-BJUDXGSMSA-N iodomethane Chemical group I[11CH3] INQOMBQAUSQDDS-BJUDXGSMSA-N 0.000 claims 1
HTUMBQDCCIXGCV-UHFFFAOYSA-N lead oxide Chemical compound [O-2].[Pb+2] HTUMBQDCCIXGCV-UHFFFAOYSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 claims 1
HWXUFGWILJZRBU-UHFFFAOYSA-N n-[2-[4-[[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]amino]piperidin-1-yl]ethyl]-[1,3]thiazolo[4,5-c]pyridin-2-amine Chemical compound C1=CC(F)=CC=C1CN1C2=CC=CC=C2N=C1NC1CCN(CCNC=2SC3=CC=NC=C3N=2)CC1 HWXUFGWILJZRBU-UHFFFAOYSA-N 0.000 claims 1
230000001387 anti-histamine Effects 0.000 abstract description 4
208000026935 allergic disease Diseases 0.000 abstract description 3
239000000739 antihistaminic agent Substances 0.000 abstract description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 123
239000000203 mixture Substances 0.000 description 104
239000002585 base Substances 0.000 description 86
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 81
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 75
239000000543 intermediate Substances 0.000 description 73
239000003480 eluent Substances 0.000 description 62
229910001868 water Inorganic materials 0.000 description 56
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
239000000047 product Substances 0.000 description 47
238000006243 chemical reaction Methods 0.000 description 39
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
229960001701 chloroform Drugs 0.000 description 34
239000000243 solution Substances 0.000 description 30
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
229920006395 saturated elastomer Polymers 0.000 description 27
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 26
239000011541 reaction mixture Substances 0.000 description 26
239000003153 chemical reaction reagent Substances 0.000 description 24
238000004440 column chromatography Methods 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
229910021529 ammonia Inorganic materials 0.000 description 19
239000000284 extract Substances 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 18
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
239000003054 catalyst Substances 0.000 description 17
241000700159 Rattus Species 0.000 description 16
239000000741 silica gel Substances 0.000 description 16
229910002027 silica gel Inorganic materials 0.000 description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
238000003756 stirring Methods 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000000499 gel Substances 0.000 description 12
125000005843 halogen group Chemical group 0.000 description 12
150000002431 hydrogen Chemical class 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
230000000875 corresponding effect Effects 0.000 description 11
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 10
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
238000007792 addition Methods 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 9
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
229920002055 compound 48/80 Polymers 0.000 description 9
UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(II) oxide Inorganic materials [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 9
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
238000010992 reflux Methods 0.000 description 8
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 6
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
150000004682 monohydrates Chemical class 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
210000002784 stomach Anatomy 0.000 description 6
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 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
230000037396 body weight Effects 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
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 4
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
230000000172 allergic effect Effects 0.000 description 4
208000010668 atopic eczema Diseases 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
125000001309 chloro group Chemical group Cl* 0.000 description 4
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 4
230000002496 gastric effect Effects 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
230000003902 lesion Effects 0.000 description 4
231100000225 lethality Toxicity 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 3
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
125000001246 bromo group Chemical group Br* 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000003610 charcoal Substances 0.000 description 3
210000005069 ears Anatomy 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000000762 glandular Effects 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
125000002346 iodo group Chemical group I* 0.000 description 3
150000002540 isothiocyanates Chemical class 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
125000003386 piperidinyl group Chemical group 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
239000011591 potassium Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
239000007858 starting material Substances 0.000 description 3
229930192474 thiophene Natural products 0.000 description 3
VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
239000004215 Carbon black (E152) Substances 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
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
JCMWSVNNSPUNER-UHFFFAOYSA-N N,O-dimethyltyramine Chemical compound CNCCC1=CC=C(OC)C=C1 JCMWSVNNSPUNER-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
238000007126 N-alkylation reaction Methods 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 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
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
241000534944 Thia Species 0.000 description 2
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
230000002152 alkylating effect Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
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IMLIPHSGYFXWAA-UHFFFAOYSA-N ethyl 4-(1h-benzimidazol-2-ylamino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=NC2=CC=CC=C2N1 IMLIPHSGYFXWAA-UHFFFAOYSA-N 0.000 description 1
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238000005187 foaming Methods 0.000 description 1
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239000012458 free base Substances 0.000 description 1
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230000002140 halogenating effect Effects 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
239000000938 histamine H1 antagonist Substances 0.000 description 1
235000003642 hunger Nutrition 0.000 description 1
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150000004678 hydrides Chemical class 0.000 description 1
125000001145 hydrido group Chemical group *[H] 0.000 description 1
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239000008172 hydrogenated vegetable oil Substances 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
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238000011065 in-situ storage Methods 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
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150000002500 ions Chemical class 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
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
150000002576 ketones Chemical class 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
YOFNWWZZELAVRX-UHFFFAOYSA-N methanethione Chemical compound S=[CH+] YOFNWWZZELAVRX-UHFFFAOYSA-N 0.000 description 1
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
229960001186 methysergide Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
XODMOHWEZASFFP-UHFFFAOYSA-N n-(5-bromo-1,3,4-thiadiazol-2-yl)acetamide Chemical compound CC(=O)NC1=NN=C(Br)S1 XODMOHWEZASFFP-UHFFFAOYSA-N 0.000 description 1
LLRJMQQFKMGUBC-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-4-nitropyridin-3-amine Chemical compound [O-][N+](=O)C1=CC=NC=C1NCC1=CC=C(F)C=C1 LLRJMQQFKMGUBC-UHFFFAOYSA-N 0.000 description 1
QRGLDPVAEILBCX-UHFFFAOYSA-N n-piperidin-4-yl-1-(pyridin-2-ylmethyl)benzimidazol-2-amine;trihydrobromide Chemical compound Br.Br.Br.C1CNCCC1NC1=NC2=CC=CC=C2N1CC1=CC=CC=N1 QRGLDPVAEILBCX-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
229940100688 oral solution Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229940068918 polyethylene glycol 400 Drugs 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
CSIGAEASXSGNKS-UHFFFAOYSA-N propane-1,1,3-triol Chemical compound OCCC(O)O CSIGAEASXSGNKS-UHFFFAOYSA-N 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
206010040560 shock Diseases 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000037351 starvation Effects 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000004149 thio group Chemical group *S* 0.000 description 1
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
101150068774 thyX gene Proteins 0.000 description 1
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
238000005303 weighing Methods 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Landscapes

Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000564954A 1983-11-30 1988-04-22 Heterocycle bicyclique contenant des n-(heterocycle, bicyclique)-4-piperidinamines Expired - Fee Related CA1330081C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000564954A CA1330081C (fr)	1983-11-30	1988-04-22	Heterocycle bicyclique contenant des n-(heterocycle, bicyclique)-4-piperidinamines

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US55674283A	1983-11-30	1983-11-30
US556,742		1983-11-30
US660,608		1984-10-12
US06/660,608 US4695569A (en)	1983-11-30	1984-10-12	Bicyclic heterocyclyl containing N-(bicyclic heterocyclyl)-4-piperidinamines
CA000468587A CA1257258A (fr)	1983-11-30	1984-11-26	N-(heterocyclyle bicyclique)-4-piperidinamines
CA000564954A CA1330081C (fr)	1983-11-30	1988-04-22	Heterocycle bicyclique contenant des n-(heterocycle, bicyclique)-4-piperidinamines

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000468587A Division CA1257258A (fr)	1983-11-30	1984-11-26	N-(heterocyclyle bicyclique)-4-piperidinamines

Publications (1)

Publication Number	Publication Date
CA1330081C true CA1330081C (fr)	1994-06-07

Family

ID=27167478

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000564954A Expired - Fee Related CA1330081C (fr)	1983-11-30	1988-04-22	Heterocycle bicyclique contenant des n-(heterocycle, bicyclique)-4-piperidinamines

Country Status (1)

Country	Link
CA (1)	CA1330081C (fr)

1988
- 1988-04-22 CA CA000564954A patent/CA1330081C/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
2000-06-07	MKLA	Lapsed

Publication	Publication Date	Title
CA1257258A (fr)	1989-07-11	N-(heterocyclyle bicyclique)-4-piperidinamines
CA1267889A (fr)	1990-04-17	(4-piperidinylmethyl et hetero)purines
EP0145037B1 (fr)	1989-01-18	N-(bicyclique hétérocyclyl)-4 pipéridinamines
KR870001046B1 (ko)	1987-05-26	N-(4-피페리딘일) 비사이클 축합 2-이미다졸아민 유도체의 제조방법
EP0099139B1 (fr)	1987-02-11	N-(Bicyclo-hétérocyclo)-4-pipéridinamines
EP0151826B1 (fr)	1993-03-31	Pipéridines méthyl-4 dont le groupe méthyl est substitué par un groupe hétérocyclique bicylique et pipéridines avec un hétéroatome lié en position 4 et substitué par un groupe hétérocyclique
KR100206723B1 (ko)	1999-07-01	신규 치환된 티아졸릴 및 치환된 피리디닐 유도체
JP3070951B2 (ja)	2000-07-31	新規なオキサゾリル誘導体
AU2006254335A1 (en)	2006-12-07	2-oxo-1-pyrrolidine derivatives and their therapeutic use on the central nervous system
EP0297661B1 (fr)	1992-09-16	[(Hétérocyclyl bicyclique) méthyl et -hétéro]hexahydro-1H-azépines et -pyrrolidines
KR880000044B1 (ko)	1988-02-20	N-(비사이클 헤테로사이클릴)-4-피페리딘아민의 제조 방법
NZ231787A (en)	1991-07-26	Compounds containing at least 3 separate nitrogen containing rings; anti allergic compositions
CA1330081C (fr)	1994-06-07	Heterocycle bicyclique contenant des n-(heterocycle, bicyclique)-4-piperidinamines
US5126339A (en)	1992-06-30	Anti-allergic bicyclic heterocyclyl-containing N-(bicyclic heterocyclyl)-4-piperidinamines
US5025014A (en)	1991-06-18	Bicyclic heterocyclyl containing N-(bicyclic heterocyclyl)-4-piperidinamines as pharmaceuticals
KR880000489B1 (ko)	1988-04-08	N-(비사이클 헤테로사이클릴)-4-피페리딘 아민의 제조방법
US4888426A (en)	1989-12-19	1-(5-methyl-furan-2-ylmethyl)-N-(4-piperidinyl)imidazo [4,5-6]pyridine-2-amine
KR880000785B1 (ko)	1988-05-09	N-(비사이클 헤테로사이클릴)-4-피페리딘아민의 제조방법
PH26643A (en)	1992-09-04	Bicyclic heterocyclic containing N-(bicyclic hetero-cyclyl)-4-piperidinamines
IE57722B1 (en)	1993-03-24	N-(bicyclic heterocyclyl)-4-piperidinamines