NO323841B1 - Kinolon-2(1H)-on derivater, fremgangsmate for deres fremstilling, medisinsk produkt samt farmasoytisk preparat. - Google Patents

Kinolon-2(1H)-on derivater, fremgangsmate for deres fremstilling, medisinsk produkt samt farmasoytisk preparat. Download PDF

Info

Publication number: NO323841B1
Authority: NO; Norway
Prior art keywords: group; quinolone; thieno; ethyl; piperazinyl
Prior art date: 1995-09-15

Application number

NO19981141A

Other languages

English (en)

Norwegian (no)

Other versions

NO981141D0 (no

NO981141L (no

Inventor

Michel Aletru

Gary Mccourt

Genevieve Dellac

Christian Hoornaert

Original Assignee

Sanofi Aventis

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-09-15

Filing date

1998-03-13

Publication date

2007-07-09

1995-09-15 Priority claimed from FR9510815A external-priority patent/FR2738822B1/fr

1995-09-21 Priority claimed from FR9511083A external-priority patent/FR2739100B1/fr

1998-03-13 Application filed by Sanofi Aventis filed Critical Sanofi Aventis

1998-03-13 Publication of NO981141D0 publication Critical patent/NO981141D0/no

1998-05-15 Publication of NO981141L publication Critical patent/NO981141L/no

2007-07-09 Publication of NO323841B1 publication Critical patent/NO323841B1/no

Links

238000000034 method Methods 0.000 title claims description 11
229940127554 medical product Drugs 0.000 title claims description 3
238000002360 preparation method Methods 0.000 title description 4
239000008194 pharmaceutical composition Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 101
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
-1 4- (thieno [3,2-c] pyridin-4-yl) -piperazin-1-yl group Chemical group 0.000 claims abstract description 17
125000000217 alkyl group Chemical group 0.000 claims abstract description 17
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 6
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
125000005843 halogen group Chemical group 0.000 claims abstract description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
RVGRTFBJOXMFAX-UHFFFAOYSA-N 4-piperazin-1-ylthieno[3,2-c]pyridine Chemical compound C1CNCCN1C1=NC=CC2=C1C=CS2 RVGRTFBJOXMFAX-UHFFFAOYSA-N 0.000 claims description 8
ABERUOJGWHYBJL-UHFFFAOYSA-N (4-fluorophenyl)-piperidin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)C1CCNCC1 ABERUOJGWHYBJL-UHFFFAOYSA-N 0.000 claims description 5
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 4
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
OHOAILOYEDMLGG-UHFFFAOYSA-N 4-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6-methoxy-1h-quinolin-2-one Chemical compound C12=CC(OC)=CC=C2NC(=O)C=C1CCN(CC1)CCC1C(=O)C1=CC=C(F)C=C1 OHOAILOYEDMLGG-UHFFFAOYSA-N 0.000 claims 1
XBDOVZHTWHOLLW-UHFFFAOYSA-N 6-chloro-1-methyl-4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]quinolin-2-one Chemical compound C=1C(=O)N(C)C2=CC=C(Cl)C=C2C=1CCN(CC1)CCN1C1=NC=CC2=C1C=CS2 XBDOVZHTWHOLLW-UHFFFAOYSA-N 0.000 claims 1
TXPOQTMXPOWTJH-UHFFFAOYSA-N 6-chloro-4-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-1-methylquinolin-2-one Chemical compound C=1C(=O)N(C)C2=CC=C(Cl)C=C2C=1CCN(CC1)CCC1C(=O)C1=CC=C(F)C=C1 TXPOQTMXPOWTJH-UHFFFAOYSA-N 0.000 claims 1
RKJKREPLDPCKKP-UHFFFAOYSA-N 6-fluoro-1-methyl-4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]quinolin-2-one Chemical compound C=1C(=O)N(C)C2=CC=C(F)C=C2C=1CCN(CC1)CCN1C1=NC=CC2=C1C=CS2 RKJKREPLDPCKKP-UHFFFAOYSA-N 0.000 claims 1
HHIOQLDBIQXLIC-UHFFFAOYSA-N 6-hydroxy-1-methyl-4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]quinolin-2-one Chemical compound C=1C(=O)N(C)C2=CC=C(O)C=C2C=1CCN(CC1)CCN1C1=NC=CC2=C1C=CS2 HHIOQLDBIQXLIC-UHFFFAOYSA-N 0.000 claims 1
QPKORTUBOTVXPA-UHFFFAOYSA-N 6-methyl-4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]-1h-quinolin-2-one Chemical compound C12=CC(C)=CC=C2NC(=O)C=C1CCN(CC1)CCN1C1=NC=CC2=C1C=CS2 QPKORTUBOTVXPA-UHFFFAOYSA-N 0.000 claims 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
125000001309 chloro group Chemical group Cl* 0.000 claims 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
229910052731 fluorine Inorganic materials 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 abstract description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 abstract 1
125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
239000000203 mixture Substances 0.000 description 66
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
239000000047 product Substances 0.000 description 35
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
239000011541 reaction mixture Substances 0.000 description 24
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
239000000243 solution Substances 0.000 description 20
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000007787 solid Substances 0.000 description 17
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
239000012074 organic phase Substances 0.000 description 15
238000010992 reflux Methods 0.000 description 15
239000000725 suspension Substances 0.000 description 15
229910052938 sodium sulfate Inorganic materials 0.000 description 14
235000011152 sodium sulphate Nutrition 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
238000001816 cooling Methods 0.000 description 13
239000000377 silicon dioxide Substances 0.000 description 13
235000017557 sodium bicarbonate Nutrition 0.000 description 13
229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
239000000706 filtrate Substances 0.000 description 12
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
238000003756 stirring Methods 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
238000000354 decomposition reaction Methods 0.000 description 11
238000010828 elution Methods 0.000 description 11
238000003818 flash chromatography Methods 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
229910021529 ammonia Inorganic materials 0.000 description 9
239000002904 solvent Substances 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
239000012279 sodium borohydride Substances 0.000 description 7
229910000033 sodium borohydride Inorganic materials 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 6
229960003708 sumatriptan Drugs 0.000 description 6
239000000872 buffer Substances 0.000 description 5
238000001035 drying Methods 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000001914 filtration Methods 0.000 description 5
210000000056 organ Anatomy 0.000 description 5
229940076279 serotonin Drugs 0.000 description 5
IWUSEHGANVYEQR-UHFFFAOYSA-N (2,6-dioxo-3h-pyran-4-yl) acetate Chemical compound CC(=O)OC1=CC(=O)OC(=O)C1 IWUSEHGANVYEQR-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
230000008602 contraction Effects 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000000126 substance Substances 0.000 description 4
ZBNXJBFROPBBCC-UHFFFAOYSA-N 4-(2-chloroethyl)-6-methoxy-1h-quinolin-2-one Chemical compound N1C(=O)C=C(CCCl)C2=CC(OC)=CC=C21 ZBNXJBFROPBBCC-UHFFFAOYSA-N 0.000 description 3
UOSXHELVDCMRDP-UHFFFAOYSA-N 4-(2-chloroethyl)-6-nitro-1h-quinolin-2-one Chemical compound N1C(=O)C=C(CCCl)C2=CC([N+](=O)[O-])=CC=C21 UOSXHELVDCMRDP-UHFFFAOYSA-N 0.000 description 3
FCEKDEBSESGRDL-UHFFFAOYSA-N 4-(2-hydroxyethyl)-1-methyl-2-oxoquinoline-6-carbonitrile Chemical compound C1=C(C#N)C=C2C(CCO)=CC(=O)N(C)C2=C1 FCEKDEBSESGRDL-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
241000700159 Rattus Species 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
239000003420 antiserotonin agent Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
210000003191 femoral vein Anatomy 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
230000009870 specific binding Effects 0.000 description 3
229950001675 spiperone Drugs 0.000 description 3
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 3
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
PPRXDTMAYMNTSV-UHFFFAOYSA-N 2-(6-chloro-1-methyl-2-oxoquinolin-4-yl)acetic acid Chemical compound C1=C(Cl)C=C2C(CC(O)=O)=CC(=O)N(C)C2=C1 PPRXDTMAYMNTSV-UHFFFAOYSA-N 0.000 description 2
NZVXGVBWKLNEDV-UHFFFAOYSA-N 2-(6-cyano-1-methyl-2-oxoquinolin-4-yl)acetic acid Chemical compound C1=C(C#N)C=C2C(CC(O)=O)=CC(=O)N(C)C2=C1 NZVXGVBWKLNEDV-UHFFFAOYSA-N 0.000 description 2
XKZAYVQNKUMTSZ-UHFFFAOYSA-N 2-(6-fluoro-1-methyl-2-oxoquinolin-4-yl)acetic acid Chemical compound C1=C(F)C=C2C(CC(O)=O)=CC(=O)N(C)C2=C1 XKZAYVQNKUMTSZ-UHFFFAOYSA-N 0.000 description 2
JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 2
SJLMITFMNDOSJI-UHFFFAOYSA-N 3-acetyloxy-5-[(4-chlorophenyl)methylamino]-5-oxopent-2-enoic acid Chemical compound CC(=O)OC(=CC(O)=O)CC(=O)NCC1=CC=C(Cl)C=C1 SJLMITFMNDOSJI-UHFFFAOYSA-N 0.000 description 2
BOHJSUWGUHQCDO-UHFFFAOYSA-N 3-acetyloxy-5-[(4-methoxyphenyl)methylamino]-5-oxopent-2-enoic acid Chemical compound COC1=CC=C(CNC(=O)CC(OC(C)=O)=CC(O)=O)C=C1 BOHJSUWGUHQCDO-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
FRGGVDJQPNKQCS-UHFFFAOYSA-N 4-(2-chloroethyl)-6-fluoro-1-methylquinolin-2-one Chemical compound C1=C(F)C=C2C(CCCl)=CC(=O)N(C)C2=C1 FRGGVDJQPNKQCS-UHFFFAOYSA-N 0.000 description 2
AROBVBZTYCFNQH-UHFFFAOYSA-N 4-(2-hydroxyethyl)-6-methoxy-1h-quinolin-2-one Chemical compound N1C(=O)C=C(CCO)C2=CC(OC)=CC=C21 AROBVBZTYCFNQH-UHFFFAOYSA-N 0.000 description 2
XBJMDWKLBQPCAY-UHFFFAOYSA-N 6-amino-4-(2-chloroethyl)-1h-quinolin-2-one;hydrochloride Chemical compound Cl.N1C(=O)C=C(CCCl)C2=CC(N)=CC=C21 XBJMDWKLBQPCAY-UHFFFAOYSA-N 0.000 description 2
KSLCKYGESXPNNB-UHFFFAOYSA-N 6-amino-4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C12=CC(N)=CC=C2NC(=O)C=C1CCN(CC1)CCN1C1=NC=CC2=C1C=CS2 KSLCKYGESXPNNB-UHFFFAOYSA-N 0.000 description 2
ZKFJZZHAPNFBGW-UHFFFAOYSA-N 6-chloro-4-(2-chloroethyl)-1-methylquinolin-2-one Chemical compound C1=C(Cl)C=C2C(CCCl)=CC(=O)N(C)C2=C1 ZKFJZZHAPNFBGW-UHFFFAOYSA-N 0.000 description 2
QAQMEOCWEXXMMC-UHFFFAOYSA-N 6-chloro-4-(2-hydroxyethyl)-1-methylquinolin-2-one Chemical compound C1=C(Cl)C=C2C(CCO)=CC(=O)N(C)C2=C1 QAQMEOCWEXXMMC-UHFFFAOYSA-N 0.000 description 2
UBEJEMJDQBIZFG-UHFFFAOYSA-N 6-fluoro-1-methyl-4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]quinolin-2-one;hydrochloride Chemical compound Cl.C=1C(=O)N(C)C2=CC=C(F)C=C2C=1CCN(CC1)CCN1C1=NC=CC2=C1C=CS2 UBEJEMJDQBIZFG-UHFFFAOYSA-N 0.000 description 2
KYZANCROVNIOPH-UHFFFAOYSA-N 6-methoxy-4-[2-(4-thieno[3,2-c]pyridin-4-ylpiperazin-1-yl)ethyl]-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C12=CC(OC)=CC=C2NC(=O)C=C1CCN(CC1)CCN1C1=NC=CC2=C1C=CS2 KYZANCROVNIOPH-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
230000004872 arterial blood pressure Effects 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
230000027455 binding Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
210000001715 carotid artery Anatomy 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
ATMXJULQABHEMJ-UHFFFAOYSA-N methyl 2-(6-chloro-1-methyl-2h-quinolin-4-yl)acetate Chemical compound C1=C(Cl)C=C2C(CC(=O)OC)=CCN(C)C2=C1 ATMXJULQABHEMJ-UHFFFAOYSA-N 0.000 description 2
PXEKRKVQLLQVKQ-UHFFFAOYSA-N methyl 2-(6-cyano-1-methyl-2-oxoquinolin-4-yl)acetate Chemical compound C1=C(C#N)C=C2C(CC(=O)OC)=CC(=O)N(C)C2=C1 PXEKRKVQLLQVKQ-UHFFFAOYSA-N 0.000 description 2
DTGBIEKOTZHTCU-UHFFFAOYSA-N methyl 2-(6-fluoro-1-methyl-2-oxoquinolin-4-yl)acetate Chemical compound C1=C(F)C=C2C(CC(=O)OC)=CC(=O)N(C)C2=C1 DTGBIEKOTZHTCU-UHFFFAOYSA-N 0.000 description 2
KFBKLTYCIDUGEO-UHFFFAOYSA-N n-[4-(2-chloroethyl)-2-oxo-1h-quinolin-6-yl]acetamide;hydrochloride Chemical compound Cl.N1C(=O)C=C(CCCl)C2=CC(NC(=O)C)=CC=C21 KFBKLTYCIDUGEO-UHFFFAOYSA-N 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
229960001412 pentobarbital Drugs 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
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Classifications

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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

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Animal Behavior & Ethology (AREA)
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Chemical Kinetics & Catalysis (AREA)
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Diabetes (AREA)
Hematology (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

NO19981141A 1995-09-15 1998-03-13 Kinolon-2(1H)-on derivater, fremgangsmate for deres fremstilling, medisinsk produkt samt farmasoytisk preparat. NO323841B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR9510815A FR2738822B1 (fr)	1995-09-15	1995-09-15	Derives de 4-(omega-(4-(thieno(3,2-c)pyridin-4-yl)piperazin- 1-yl)alkyl)quinolein-2(1h)-one, leur preparation et leur application en therapeutique
FR9511083A FR2739100B1 (fr)	1995-09-21	1995-09-21	Derives de 4-(omega-(4-(4-fluorobenzoyl)piperidin-1-yl)- alkyl)quinolein-2(1h)-one, leur preparation et leur application en therapeutique
PCT/FR1996/001401 WO1997010238A1 (fr)	1995-09-15	1996-09-12	Derives de quinolein-2(1h)-one comme antagonistes de la serotonine

Publications (3)

Publication Number	Publication Date
NO981141D0 NO981141D0 (no)	1998-03-13
NO981141L NO981141L (no)	1998-05-15
NO323841B1 true NO323841B1 (no)	2007-07-09

Family

ID=26232206

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19981141A NO323841B1 (no)	1995-09-15	1998-03-13	Kinolon-2(1H)-on derivater, fremgangsmate for deres fremstilling, medisinsk produkt samt farmasoytisk preparat.

Country Status (29)

Country	Link
US (1)	US5958924A (pl)
EP (1)	EP0850235B1 (pl)
JP (1)	JP3335362B2 (pl)
KR (1)	KR100422850B1 (pl)
CN (1)	CN1094490C (pl)
AR (1)	AR003996A1 (pl)
AT (1)	ATE187172T1 (pl)
AU (1)	AU715879B2 (pl)
BG (1)	BG63779B1 (pl)
BR (1)	BR9610579A (pl)
CA (1)	CA2228038C (pl)
CO (1)	CO4750663A1 (pl)
CZ (1)	CZ288149B6 (pl)
DE (1)	DE69605430T2 (pl)
DK (1)	DK0850235T3 (pl)
EE (1)	EE04116B1 (pl)
ES (1)	ES2142089T3 (pl)
GR (1)	GR3032618T3 (pl)
HU (1)	HU222745B1 (pl)
IL (1)	IL123600A (pl)
NO (1)	NO323841B1 (pl)
NZ (1)	NZ318436A (pl)
PL (1)	PL184808B1 (pl)
RU (1)	RU2167874C2 (pl)
SI (1)	SI0850235T1 (pl)
SK (1)	SK282222B6 (pl)
TR (1)	TR199800464T1 (pl)
UA (1)	UA44332C2 (pl)
WO (1)	WO1997010238A1 (pl)

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CA2735764C (en)	2008-09-02	2016-06-14	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors
SI2344471T1 (sl) *	2008-10-02	2013-11-29	Taisho Pharmaceutical Co., Ltd.	Derivat 7-piperidinoalkil-3,4-dihidrokvinolona
BRPI0921333A2 (pt)	2008-11-28	2015-12-29	Addex Pharmaceuticals Sa	derivados de indol e benzoxazina como moduladores de receptores de glutamato metabotrópicos
NZ596078A (en)	2009-05-12	2013-06-28	Janssen Pharmaceuticals Inc	1,2,4-TRIAZOLO [4,3-a] PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OR PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
EA020671B1 (ru)	2009-05-12	2014-12-30	Янссен Фармасьютикалз, Инк.	ПРОИЗВОДНЫЕ 1,2,4-ТРИАЗОЛО[4,3-a]ПИРИДИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ПОЛОЖИТЕЛЬНЫХ АЛЛОСТЕРИЧЕСКИХ МОДУЛЯТОРОВ РЕЦЕПТОРОВ mGluR2
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CN103298810B (zh)	2010-11-08	2016-03-16	杨森制药公司	1,2,4-三唑并[4,3-a]吡啶衍生物及其作为MGLUR2受体的正变构调节剂的用途
CA2815002C (en)	2010-11-08	2019-10-22	Janssen Pharmaceuticals, Inc.	1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
JO3368B1 (ar)	2013-06-04	2019-03-13	Janssen Pharmaceutica Nv	مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JO3367B1 (ar)	2013-09-06	2019-03-13	Janssen Pharmaceutica Nv	مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2
LT3431106T (lt)	2014-01-21	2021-02-10	Janssen Pharmaceutica Nv	Deriniai, apimantys 2 potipio metabotropinio glutamaterginio receptoriaus teigiamus alosterinius moduliatorius arba ortosterinius agonistus, ir jų panaudojimas
KR102414246B1 (ko)	2014-01-21	2022-06-27	얀센 파마슈티카 엔.브이.	대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도
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1996
- 1996-09-12 BR BR9610579A patent/BR9610579A/pt not_active Application Discontinuation
- 1996-09-12 CA CA002228038A patent/CA2228038C/en not_active Expired - Fee Related
- 1996-09-12 AR ARP960104322A patent/AR003996A1/es active IP Right Grant
- 1996-09-12 EP EP96931112A patent/EP0850235B1/fr not_active Expired - Lifetime
- 1996-09-12 CO CO96048698A patent/CO4750663A1/es unknown
- 1996-09-12 SI SI9630151T patent/SI0850235T1/xx unknown
- 1996-09-12 PL PL96325467A patent/PL184808B1/pl not_active IP Right Cessation
- 1996-09-12 UA UA98031235A patent/UA44332C2/uk unknown
- 1996-09-12 TR TR1998/00464T patent/TR199800464T1/xx unknown
- 1996-09-12 ES ES96931112T patent/ES2142089T3/es not_active Expired - Lifetime
- 1996-09-12 CZ CZ1998786A patent/CZ288149B6/cs not_active IP Right Cessation
- 1996-09-12 WO PCT/FR1996/001401 patent/WO1997010238A1/fr not_active Ceased
- 1996-09-12 IL IL12360096A patent/IL123600A/en not_active IP Right Cessation
- 1996-09-12 SK SK346-98A patent/SK282222B6/sk not_active IP Right Cessation
- 1996-09-12 RU RU98106501/04A patent/RU2167874C2/ru not_active IP Right Cessation
- 1996-09-12 AU AU69919/96A patent/AU715879B2/en not_active Ceased
- 1996-09-12 EE EE9800089A patent/EE04116B1/xx not_active IP Right Cessation
- 1996-09-12 NZ NZ318436A patent/NZ318436A/xx not_active IP Right Cessation
- 1996-09-12 KR KR10-1998-0701920A patent/KR100422850B1/ko not_active Expired - Fee Related
- 1996-09-12 DK DK96931112T patent/DK0850235T3/da active
- 1996-09-12 DE DE69605430T patent/DE69605430T2/de not_active Expired - Lifetime
- 1996-09-12 HU HU9802940A patent/HU222745B1/hu not_active IP Right Cessation
- 1996-09-12 AT AT96931112T patent/ATE187172T1/de active
- 1996-09-12 US US09/011,482 patent/US5958924A/en not_active Expired - Lifetime
- 1996-09-12 JP JP51170797A patent/JP3335362B2/ja not_active Expired - Fee Related
- 1996-09-12 CN CN96198333A patent/CN1094490C/zh not_active Expired - Fee Related
1998
- 1998-03-11 BG BG102316A patent/BG63779B1/bg unknown
- 1998-03-13 NO NO19981141A patent/NO323841B1/no not_active IP Right Cessation
2000
- 2000-02-09 GR GR20000400317T patent/GR3032618T3/el unknown

Also Published As

Publication number	Publication date
NO981141D0 (no)	1998-03-13
NZ318436A (en)	1999-02-25
RU2167874C2 (ru)	2001-05-27
IL123600A0 (en)	1998-10-30
HU222745B1 (hu)	2003-09-29
MX9802028A (es)	1998-09-30
PL184808B1 (pl)	2002-12-31
CZ78698A3 (cs)	1998-06-17
IL123600A (en)	2001-05-20
EP0850235B1 (fr)	1999-12-01
SI0850235T1 (en)	2000-04-30
SK34698A3 (en)	1998-08-05
DK0850235T3 (da)	2000-05-29
EE04116B1 (et)	2003-08-15
EP0850235A1 (fr)	1998-07-01
CO4750663A1 (es)	1999-03-31
GR3032618T3 (en)	2000-05-31
CZ288149B6 (en)	2001-05-16
DE69605430T2 (de)	2000-07-13
PL325467A1 (en)	1998-07-20
UA44332C2 (uk)	2002-02-15
NO981141L (no)	1998-05-15
AU6991996A (en)	1997-04-01
SK282222B6 (sk)	2001-12-03
HK1014868A1 (en)	1999-10-08
AU715879B2 (en)	2000-02-10
TR199800464T1 (xx)	1998-05-21
DE69605430D1 (de)	2000-01-05
ES2142089T3 (es)	2000-04-01
KR19990044666A (ko)	1999-06-25
BG63779B1 (bg)	2002-12-29
AR003996A1 (es)	1998-09-30
CA2228038C (en)	2009-04-21
CN1094490C (zh)	2002-11-20
HUP9802940A2 (hu)	1999-05-28
CN1202168A (zh)	1998-12-16
HUP9802940A3 (en)	2001-11-28
CA2228038A1 (en)	1997-03-20
JPH11514982A (ja)	1999-12-21
WO1997010238A1 (fr)	1997-03-20
ATE187172T1 (de)	1999-12-15
BR9610579A (pt)	1999-07-06
KR100422850B1 (ko)	2004-07-23
US5958924A (en)	1999-09-28
BG102316A (en)	1999-03-31
EE9800089A (et)	1998-10-15
JP3335362B2 (ja)	2002-10-15

Legal Events

Date	Code	Title	Description
2013-04-22	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
RU2167874C2 (ru)	2001-05-27	Производные хинолин-2(1н)-она, способы их получения, лекарственное средство и фармацевтическая композиция на их основе
CA2557541C (en)	2014-12-16	Pyrimidine derivatives
JP3110765B2 (ja)	2000-11-20	ピリド［２，３−ｄ］ピリミジン誘導体及びその医薬組成物
PL180679B1 (en)	2001-03-30	Derivatives of pyridazinoquinoline
CZ290924B6 (cs)	2002-11-13	Aromatické sloučeniny, způsoby jejich přípravy a farmaceutické prostředky, které je obsahují
US6197768B1 (en)	2001-03-06	Pyridocarbazole derivatives having cgmp-pde inhibitory activity
EP3240783B1 (en)	2018-11-21	New benzimidazole derivatives as antihistamine agents
ES2306906T3 (es)	2008-11-16	Nuevos derivados triciclicos como antagonistas de ltd4.
EP0750614A1 (en)	1997-01-02	Quinazolinyl-amino derivatives having alpha-antagonist activity
AU2002325493B2 (en)	2005-06-09	Condensed Polycyclic Compounds
FR2761071A1 (fr)	1998-09-25	Derives de quinolein-2(1h)-one et de dihydroquinolein-2(1h)- one, leur preparation et leur application en therapeutique
JPH07267951A (ja)	1995-10-17	アンジオテンシンｉｉ拮抗剤としての新規イミダゾピリジン誘導体
CS226901B1 (en)	1984-04-16	Thiazoloisoquinoline derivatives
MXPA98002028A (en)	1998-11-16	Quinolein-2 (1h) -ona derivatives as seroton antagonists
JP4352917B2 (ja)	2009-10-28	医薬組成物
HK1014868B (en)	2000-10-27	Quinolein-2(1h)-one derivatives as serotonin antagonists
KR100295148B1 (ko)	2001-09-07	피리다지노퀴놀린 화합물
FR2738822A1 (fr)	1997-03-21	Derives de 4-(omega-(4-(thieno(3,2-c)pyridin-4-yl)piperazin- 1-yl)alkyl)quinolein-2(1h)-one, leur preparation et leur application en therapeutique
JPH07620B2 (ja)	1995-01-11	縮合イミダゾピリジン誘導体
FR2739100A1 (fr)	1997-03-28	Derives de 4-(omega-(4-(4-fluorobenzoyl)piperidin-1-yl)- alkyl)quinolein-2(1h)-one, leur preparation et leur application en therapeutique
HK1240223A1 (en)	2018-05-18	New benzimidazole derivatives as antihistamine agents
HK1240223B (en)	2019-09-06	New benzimidazole derivatives as antihistamine agents
JPWO1999026946A1 (ja)	2002-09-10	ｃＧＭＰ−ＰＤＥ阻害作用を有するピリドカルバゾール誘導体
JPH05178836A (ja)	1993-07-20	アンジオテンシンｉｉ拮抗性ピリジン誘導体