CA1292989C - Pyridines hetero [f] carbocycliques en tant qu'agents dopaminergiques - Google Patents

Pyridines hetero [f] carbocycliques en tant qu'agents dopaminergiques

Info

Publication number: CA1292989C
Authority: CA; Canada
Prior art keywords: formula; compound; 6alkyl; defined above; hydrogen
Prior art date: 1987-08-20
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

CA000544960A

Other languages

English (en)

Inventor

Lawrence D. Wise

Bradley W. Caprathe

Juan C. Jaen

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.)

Warner Lambert Co LLC

Original Assignee

Warner Lambert Co LLC

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.)

1987-08-20

Filing date

1987-08-20

Publication date

1991-12-10

1987-08-20 Application filed by Warner Lambert Co LLC filed Critical Warner Lambert Co LLC

1987-08-20 Priority to CA000544960A priority Critical patent/CA1292989C/fr

1991-12-10 Application granted granted Critical

1991-12-10 Publication of CA1292989C publication Critical patent/CA1292989C/fr

2008-12-10 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

-1 carbocyclic pyridines Chemical class 0.000 title claims abstract description 32
239000003136 dopamine receptor stimulating agent Substances 0.000 title claims abstract description 9
125000005842 heteroatom Chemical group 0.000 title abstract 2
229940005501 dopaminergic agent Drugs 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 41
239000000164 antipsychotic agent Substances 0.000 claims abstract description 4
230000003291 dopaminomimetic effect Effects 0.000 claims abstract description 4
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
239000002220 antihypertensive agent Substances 0.000 claims abstract description 3
229940030600 antihypertensive agent Drugs 0.000 claims abstract description 3
230000000561 anti-psychotic effect Effects 0.000 claims abstract 2
150000001875 compounds Chemical class 0.000 claims description 243
239000000203 mixture Substances 0.000 claims description 67
239000001257 hydrogen Substances 0.000 claims description 60
229910052739 hydrogen Inorganic materials 0.000 claims description 60
239000002253 acid Substances 0.000 claims description 59
125000000217 alkyl group Chemical group 0.000 claims description 59
150000003839 salts Chemical class 0.000 claims description 56
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
125000003710 aryl alkyl group Chemical group 0.000 claims description 27
GCMNJUJAKQGROZ-UHFFFAOYSA-N 1,2-Dihydroquinolin-2-imine Chemical compound C1=CC=CC2=NC(N)=CC=C21 GCMNJUJAKQGROZ-UHFFFAOYSA-N 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical class 0.000 claims description 16
229910052987 metal hydride Inorganic materials 0.000 claims description 11
150000004681 metal hydrides Chemical class 0.000 claims description 11
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 10
230000003287 optical effect Effects 0.000 claims description 10
CIOUSPAIDCNVQU-UHFFFAOYSA-N 6-(cyclopropylmethyl)-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound S1C(N)=NC(C2=CCC3)=C1CCC2N3CC1CC1 CIOUSPAIDCNVQU-UHFFFAOYSA-N 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 7
230000007717 exclusion Effects 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
239000012442 inert solvent Substances 0.000 claims description 5
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
WNWZCNWZNSFQOZ-UHFFFAOYSA-N 4,5,5a,6,7,8-hexahydro-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound N1CCC=C2C(N=C(S3)N)=C3CCC21 WNWZCNWZNSFQOZ-UHFFFAOYSA-N 0.000 claims description 4
FDKMYOWJUBDEFD-UHFFFAOYSA-N 6-ethyl-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound CCN1CCC=C2C1CCC1=C2N=C(N)S1 FDKMYOWJUBDEFD-UHFFFAOYSA-N 0.000 claims description 4
XFJSSDHKIXXJLM-UHFFFAOYSA-N 6-methyl-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound CN1CCC=C2C1CCC1=C2N=C(N)S1 XFJSSDHKIXXJLM-UHFFFAOYSA-N 0.000 claims description 4
VOPHHPYKMCJUCP-UHFFFAOYSA-N 6-propyl-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound CCCN1CCC=C2C1CCC1=C2N=C(N)S1 VOPHHPYKMCJUCP-UHFFFAOYSA-N 0.000 claims description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
230000000903 blocking effect Effects 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 3
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
150000001805 chlorine compounds Chemical group 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 37
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 8
125000003118 aryl group Chemical group 0.000 claims 8
INJRXBVVUXJFOB-UHFFFAOYSA-N 6-butyl-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound CCCCN1CCC=C2C1CCC1=C2N=C(N)S1 INJRXBVVUXJFOB-UHFFFAOYSA-N 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 9
230000003518 presynaptic effect Effects 0.000 abstract description 5
102000015554 Dopamine receptor Human genes 0.000 abstract description 4
108050004812 Dopamine receptor Proteins 0.000 abstract description 4
229940052760 dopamine agonists Drugs 0.000 abstract description 2
208000031424 hyperprolactinemia Diseases 0.000 abstract description 2
208000015114 central nervous system disease Diseases 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
239000000243 solution Substances 0.000 description 102
125000001309 chloro group Chemical group Cl* 0.000 description 76
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
239000007787 solid Substances 0.000 description 69
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 32
239000000908 ammonium hydroxide Substances 0.000 description 32
238000006243 chemical reaction Methods 0.000 description 32
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
229910052757 nitrogen Inorganic materials 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 23
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
238000004587 chromatography analysis Methods 0.000 description 19
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 16
125000003342 alkenyl group Chemical group 0.000 description 16
150000002148 esters Chemical class 0.000 description 16
239000003921 oil Substances 0.000 description 15
239000000741 silica gel Substances 0.000 description 15
229910002027 silica gel Inorganic materials 0.000 description 15
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 14
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 14
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 14
235000019198 oils Nutrition 0.000 description 14
239000002904 solvent Substances 0.000 description 14
239000000543 intermediate Substances 0.000 description 13
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
239000000284 extract Substances 0.000 description 12
238000010992 reflux Methods 0.000 description 11
239000000725 suspension Substances 0.000 description 11
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
230000009467 reduction Effects 0.000 description 10
239000012279 sodium borohydride Substances 0.000 description 10
229910000033 sodium borohydride Inorganic materials 0.000 description 10
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 9
150000002431 hydrogen Chemical group 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000002026 chloroform extract Substances 0.000 description 8
238000005956 quaternization reaction Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
YHHBKPWMEXGLKE-UHFFFAOYSA-N 7,8-dihydro-6h-quinolin-5-one Chemical compound C1=CC=C2C(=O)CCCC2=N1 YHHBKPWMEXGLKE-UHFFFAOYSA-N 0.000 description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
239000002585 base Substances 0.000 description 7
239000012267 brine Substances 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
239000003826 tablet Substances 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
238000001816 cooling Methods 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 6
ONMHILWRKWFCRT-UHFFFAOYSA-N 2-methyl-n-(6-methyl-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-yl)propanamide Chemical compound CN1CCC=C2C(N=C(S3)NC(=O)C(C)C)=C3CCC21 ONMHILWRKWFCRT-UHFFFAOYSA-N 0.000 description 5
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
IUSWEIUYILMQES-UHFFFAOYSA-N 4,5-dihydro-[1,3]oxazolo[4,5-f]quinolin-2-amine Chemical compound C1=CC=C2C(N=C(O3)N)=C3CCC2=N1 IUSWEIUYILMQES-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 5
MUMVIYLVHVCYGI-UHFFFAOYSA-N n,n,n',n',n",n"-hexamethylmethanetriamine Chemical compound CN(C)C(N(C)C)N(C)C MUMVIYLVHVCYGI-UHFFFAOYSA-N 0.000 description 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
239000000843 powder Substances 0.000 description 5
230000008569 process Effects 0.000 description 5
239000000047 product Substances 0.000 description 5
CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical compound C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 5
HWZJQLSBBQLPAJ-UHFFFAOYSA-N 1h-pyrazolo[3,4-f]quinoline Chemical compound C1=CC2=NC=CC=C2C2=C1C=NN2 HWZJQLSBBQLPAJ-UHFFFAOYSA-N 0.000 description 4
TUWAZKGQESCABO-UHFFFAOYSA-N 3h-pyrazolo[4,3-f]quinoline Chemical compound C1=CC=C2C3=CNN=C3C=CC2=N1 TUWAZKGQESCABO-UHFFFAOYSA-N 0.000 description 4
FGNZKPVPUDIOLQ-UHFFFAOYSA-N 6-propyl-5,5a,7,8-tetrahydro-4h-[1,3]oxazolo[5,4-f]quinolin-2-amine Chemical compound CCCN1CCC=C2C1CCC1=C2OC(N)=N1 FGNZKPVPUDIOLQ-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
150000001409 amidines Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
230000031709 bromination Effects 0.000 description 4
238000005893 bromination reaction Methods 0.000 description 4
STIAPHVBRDNOAJ-UHFFFAOYSA-N carbamimidoylazanium;carbonate Chemical compound NC(N)=N.NC(N)=N.OC(O)=O STIAPHVBRDNOAJ-UHFFFAOYSA-N 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical class [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
239000003039 volatile agent Substances 0.000 description 4
GKNHAQCDYVVXIU-JGVFFNPUSA-N (4aS,8aR)-5-oxo-2,3,4,4a,6,7,8,8a-octahydroquinoline-1-carboxylic acid Chemical compound C1CCC(=O)[C@@H]2[C@@H]1N(C(=O)O)CCC2 GKNHAQCDYVVXIU-JGVFFNPUSA-N 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
JNAWYGGFPCGFTK-UHFFFAOYSA-N 2-methyl-n-(6-propyl-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-yl)propanamide Chemical compound CCCN1CCC=C2C1CCC1=C2N=C(NC(=O)C(C)C)S1 JNAWYGGFPCGFTK-UHFFFAOYSA-N 0.000 description 3
IKCQIRRLFQJYDZ-UHFFFAOYSA-N 2h-quinazolin-3-amine Chemical compound C1=CC=CC2=CN(N)CN=C21 IKCQIRRLFQJYDZ-UHFFFAOYSA-N 0.000 description 3
NEOKJHOTGOQZJT-UHFFFAOYSA-N 6-(2-phenylethyl)-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound S1C(N)=NC(C2=CCC3)=C1CCC2N3CCC1=CC=CC=C1 NEOKJHOTGOQZJT-UHFFFAOYSA-N 0.000 description 3
JSYWQQGTQYQTEI-UHFFFAOYSA-N 6-benzyl-5,5a,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-f]quinolin-2-amine Chemical compound S1C(N)=NC(C2=CCC3)=C1CCC2N3CC1=CC=CC=C1 JSYWQQGTQYQTEI-UHFFFAOYSA-N 0.000 description 3
MKASOTAJQQLMSU-UHFFFAOYSA-N 6-propyl-5,5a,7,8-tetrahydro-4h-[1,3]oxazolo[4,5-f]quinolin-2-amine Chemical compound CCCN1CCC=C2C1CCC1=C2N=C(N)O1 MKASOTAJQQLMSU-UHFFFAOYSA-N 0.000 description 3
YBUZBPXSUWAVOD-UHFFFAOYSA-N 7,8-dihydro-5h-quinolin-6-one Chemical compound C1=CC=C2CC(=O)CCC2=N1 YBUZBPXSUWAVOD-UHFFFAOYSA-N 0.000 description 3
WSLGPRZZGRXDML-UHFFFAOYSA-N 7-methyl-6,6a,8,9-tetrahydro-5h-pyrido[2,3-h]quinazolin-2-amine Chemical compound N1=C(N)N=C2C3=CCCN(C)C3CCC2=C1 WSLGPRZZGRXDML-UHFFFAOYSA-N 0.000 description 3
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
102000007527 Autoreceptors Human genes 0.000 description 3
108010071131 Autoreceptors Proteins 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
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239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
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239000000825 pharmaceutical preparation Substances 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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230000001242 postsynaptic effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
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ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
IJNJLGFTSIAHEA-UHFFFAOYSA-N prop-2-ynal Chemical compound O=CC#C IJNJLGFTSIAHEA-UHFFFAOYSA-N 0.000 description 1
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YPGKCHLORVZMGI-UHFFFAOYSA-N quinazoline;hydroiodide Chemical compound I.N1=CN=CC2=CC=CC=C21 YPGKCHLORVZMGI-UHFFFAOYSA-N 0.000 description 1
YHQSXWOXIHDVHQ-UHFFFAOYSA-N quinoline;hydrobromide Chemical compound [Br-].[NH+]1=CC=CC2=CC=CC=C21 YHQSXWOXIHDVHQ-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
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201000000980 schizophrenia Diseases 0.000 description 1
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CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000005619 secondary aliphatic amines Chemical class 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
TWEGKFXBDXYJIU-UHFFFAOYSA-M sodium;2-methylpropanoate Chemical compound [Na+].CC(C)C([O-])=O TWEGKFXBDXYJIU-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
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235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
239000000126 substance Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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239000000454 talc Substances 0.000 description 1
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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 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
150000007979 thiazole derivatives Chemical class 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
239000011345 viscous material Substances 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000544960A 1987-08-20 1987-08-20 Pyridines hetero [f] carbocycliques en tant qu'agents dopaminergiques Expired - Fee Related CA1292989C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000544960A CA1292989C (fr)	1987-08-20	1987-08-20	Pyridines hetero [f] carbocycliques en tant qu'agents dopaminergiques

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA000544960A CA1292989C (fr)	1987-08-20	1987-08-20	Pyridines hetero [f] carbocycliques en tant qu'agents dopaminergiques

Publications (1)

Publication Number	Publication Date
CA1292989C true CA1292989C (fr)	1991-12-10

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CA000544960A Expired - Fee Related CA1292989C (fr)	1987-08-20	1987-08-20	Pyridines hetero [f] carbocycliques en tant qu'agents dopaminergiques

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CA (1)	CA1292989C (fr)

1987
- 1987-08-20 CA CA000544960A patent/CA1292989C/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
1996-06-10	MKLA	Lapsed

Publication	Publication Date	Title
US4501890A (en)	1985-02-26	Trans-(±)-2,4,6-substituted-5,5a,6,7,8,9,9a,10-octahydro-pyrimido[4,5-g]quinolines
Wentland et al.	1984	Novel amino-substituted 3-quinolinecarboxylic acid antibacterial agents: synthesis and structure-activity relationships
US5298657A (en)	1994-03-29	Preparation of substituted guanidines
JPH04506071A (ja)	1992-10-22	中枢神経系活性を有する複素環系アミン
AU7644698A (en)	1998-11-13	Crf antagonistic quino- and quinazolines
CA2142721A1 (fr)	1994-03-03	Derives condenses de l'indole utilises comme antagonistes des recepteurs 5ht2c et 5ht2b
CA2308057A1 (fr)	1999-05-06	Piperazines de 1-(2-naphtyle) et de 1-(2-azanaphtyle)-4-(1-phenylmethyle)en tant que ligands pour le sous-type du recepteur de la dopamine d4
US4782058A (en)	1988-11-01	1,3,4,6,7,11b-Hexahydro-6-phenyl-2H-pyrazino-(2,1-a)isoquinolines, for anti-histamine or anti-depression treatment
CA2014062C (fr)	2000-06-13	Derives de pyridine
AU596212B2 (en)	1990-04-26	Hetero {f} fused carbocyclic pyridines as dopaminergic agents
HU196377B (en)	1988-11-28	Process for production of 2-substituated-amin-5-acethilimidasoles
CA1292989C (fr)	1991-12-10	Pyridines hetero [f] carbocycliques en tant qu'agents dopaminergiques
KR870001160B1 (ko)	1987-06-13	2-메르캅토 피리미도헥사하이드로퀴놀린 유도체의 제조방법
JP2003509494A (ja)	2003-03-11	ムスカリン拮抗薬
Cheng et al.	1995	Synthetic approaches to 2‐substituted 1‐oxo‐and 3‐oxotetrahydroisoquinolines
US4678791A (en)	1987-07-07	6-phenyl-1,2-3,4,4a,5-6,10b-octahydrobenz(h)isoquinolines useful for treating depression
US4167638A (en)	1979-09-11	Process for production of 8-NHR quinolines
DE69129790T2 (de)	1999-05-06	5-Amino-5,6,7,8-Tetrahydrochinoline und verwandte Verbindungen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
NZ205030A (en)	1986-03-14	Optically pure isomers of trans-1-n-propyl-6oxodecahydroquinoline
EP0172697B1 (fr)	1991-09-25	Octahydro-oxazolo[4,5-g]quinoléines
US4647667A (en)	1987-03-03	Octa- and deca-hydroquinoline intermediates
AU8325987A (en)	1988-06-30	Antipsychotic amino-polyhydro-benz-(iso)quinolines and intermediates
CA1259313A (fr)	1989-09-12	Composes a base de trans-dl-6-oxo-7- formyldecahydroquinoleine
US5194439A (en)	1993-03-16	N-(2,3-dihydro-1,4-benzodioxinyl)-N-substituted aminopyrido-fused cycloalkanes
US4480100A (en)	1984-10-30	[2-[(Nitropyridinyl)amino]phenyl]arymethanones