AP715A - Quinoline and quinazoline compounds useful in therapy. - Google Patents

Quinoline and quinazoline compounds useful in therapy. Download PDF

Info

Publication number: AP715A
Authority: AP; ARIPO
Prior art keywords: compound; formula; meoh; product; amino
Prior art date: 1995-12-23

Application number

APAP/P/1996/000900A

Other languages

English (en)

Other versions

AP9600900A0 (en

Inventor

Allan John Collis

David Nathan Abraham Fox

Julie Newman

Original Assignee

Pfizer Res & Dev

Pfizer Central Res

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.)

1995-12-23

Filing date

1996-12-19

Publication date

1998-12-30

1996-12-19 Application filed by Pfizer Res & Dev, Pfizer Central Res filed Critical Pfizer Res & Dev

1997-01-31 Publication of AP9600900A0 publication Critical patent/AP9600900A0/xx

1998-12-30 Application granted granted Critical

1998-12-30 Publication of AP715A publication Critical patent/AP715A/en

Links

SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims description 34
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims description 5
238000002560 therapeutic procedure Methods 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 407
150000003839 salts Chemical class 0.000 claims abstract description 12
125000004122 cyclic group Chemical group 0.000 claims abstract description 11
125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
206010004446 Benign prostatic hyperplasia Diseases 0.000 claims abstract description 8
208000004403 Prostatic Hyperplasia Diseases 0.000 claims abstract description 8
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 7
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 5
238000000034 method Methods 0.000 claims description 124
238000006243 chemical reaction Methods 0.000 claims description 76
230000008569 process Effects 0.000 claims description 25
125000000217 alkyl group Chemical group 0.000 claims description 11
229910052740 iodine Inorganic materials 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 5
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
230000009471 action Effects 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
230000000269 nucleophilic effect Effects 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
238000007363 ring formation reaction Methods 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 3
125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 2
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 573
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 344
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 198
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 136
239000000047 product Substances 0.000 description 134
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 105
239000007787 solid Substances 0.000 description 103
235000019439 ethyl acetate Nutrition 0.000 description 99
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 94
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 84
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
229910001868 water Inorganic materials 0.000 description 79
239000000243 solution Substances 0.000 description 75
239000000741 silica gel Substances 0.000 description 70
229910002027 silica gel Inorganic materials 0.000 description 70
239000000203 mixture Substances 0.000 description 61
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 55
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
239000006260 foam Substances 0.000 description 53
229910052943 magnesium sulfate Inorganic materials 0.000 description 47
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
230000002829 reductive effect Effects 0.000 description 45
239000011541 reaction mixture Substances 0.000 description 37
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
239000012044 organic layer Substances 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
239000012043 crude product Substances 0.000 description 30
238000001665 trituration Methods 0.000 description 29
238000004587 chromatography analysis Methods 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
239000000543 intermediate Substances 0.000 description 23
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
239000002904 solvent Substances 0.000 description 22
238000001914 filtration Methods 0.000 description 18
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
238000010992 reflux Methods 0.000 description 17
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
238000001816 cooling Methods 0.000 description 16
239000010410 layer Substances 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
238000005406 washing Methods 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 13
229910000069 nitrogen hydride Inorganic materials 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 12
235000019198 oils Nutrition 0.000 description 12
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 12
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 11
230000002411 adverse Effects 0.000 description 11
229920006395 saturated elastomer Polymers 0.000 description 11
239000000725 suspension Substances 0.000 description 11
ZWVMLYRJXORSEP-LURJTMIESA-N (2s)-hexane-1,2,6-triol Chemical compound OCCCC[C@H](O)CO ZWVMLYRJXORSEP-LURJTMIESA-N 0.000 description 10
238000007792 addition Methods 0.000 description 10
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 10
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
229910000029 sodium carbonate Inorganic materials 0.000 description 8
238000001035 drying Methods 0.000 description 7
XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 7
239000000377 silicon dioxide Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
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 6
239000002244 precipitate Substances 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
238000003756 stirring Methods 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
229960001802 phenylephrine Drugs 0.000 description 5
SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 5
238000000746 purification Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 4
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
239000013058 crude material Substances 0.000 description 4
239000000284 extract Substances 0.000 description 4
238000009472 formulation Methods 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
230000004044 response Effects 0.000 description 4
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
239000012346 acetyl chloride Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
244000309464 bull Species 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
239000012071 phase Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
210000002307 prostate Anatomy 0.000 description 3
YOSOSDBZAUWJJT-UHFFFAOYSA-L sodium dithionite monohydrate Chemical compound O.[Na+].[Na+].[O-]S(=O)S([O-])=O YOSOSDBZAUWJJT-UHFFFAOYSA-L 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
DSWKWGBSHIUZEQ-UHFFFAOYSA-N 2-(7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-6-yl)-6,7-dimethoxy-5-phenylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CN=CN=C4CC3)=NC(N)=C2C=1C1=CC=CC=C1 DSWKWGBSHIUZEQ-UHFFFAOYSA-N 0.000 description 2
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
ZWZFDRYYHHAVEZ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxy-5-phenylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(Cl)=NC(N)=C2C=1C1=CC=CC=C1 ZWZFDRYYHHAVEZ-UHFFFAOYSA-N 0.000 description 2
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical class C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
244000025254 Cannabis sativa Species 0.000 description 2
244000166102 Eucalyptus leucoxylon Species 0.000 description 2
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
-1 Nitronium tetrafluoroborate Chemical compound 0.000 description 2
OOMXGFUBBBFWHR-UHFFFAOYSA-N O.SS Chemical compound O.SS OOMXGFUBBBFWHR-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
239000004133 Sodium thiosulphate Substances 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
230000009989 contractile response Effects 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000003480 eluent Substances 0.000 description 2
210000003191 femoral vein Anatomy 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
QXOXUEFXRSIYSW-UHFFFAOYSA-N methyl 3-hydroxy-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(O)=C1 QXOXUEFXRSIYSW-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
229960002748 norepinephrine Drugs 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
150000003246 quinazolines Chemical class 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
239000007909 solid dosage form Substances 0.000 description 2
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239000012954 diazonium Substances 0.000 description 1
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239000000463 material Substances 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
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UVDVXQHUTBCRKT-UHFFFAOYSA-N morpholin-4-yl(piperidin-4-yl)methanone Chemical compound C1COCCN1C(=O)C1CCNCC1 UVDVXQHUTBCRKT-UHFFFAOYSA-N 0.000 description 1
LDYVCQBDZNGSAV-WCCKRBBISA-N morpholine (2S)-pyrrolidine-2-carboxylic acid Chemical compound N1CCOCC1.N1[C@H](C(=O)O)CCC1 LDYVCQBDZNGSAV-WCCKRBBISA-N 0.000 description 1
KXIBCCFSAMRWIC-UHFFFAOYSA-N morpholine-4-sulfonyl chloride Chemical compound ClS(=O)(=O)N1CCOCC1 KXIBCCFSAMRWIC-UHFFFAOYSA-N 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 1
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DYIRRTHNXPHLAZ-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-phenylquinazolin-2-yl)-1,3-dihydroisoindol-4-yl]methanesulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=C(NS(C)(=O)=O)C=CC=C4C3)=NC(N)=C2C=1C1=CC=CC=C1 DYIRRTHNXPHLAZ-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
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AVPKHOTUOHDTLW-UHFFFAOYSA-N oxane-4-carboxylic acid Chemical compound OC(=O)C1CCOCC1 AVPKHOTUOHDTLW-UHFFFAOYSA-N 0.000 description 1
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239000003182 parenteral nutrition solution Substances 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
KDHKOJFFKXGPKZ-UHFFFAOYSA-N piperidin-3-one;hydrochloride Chemical compound Cl.O=C1CCCNC1 KDHKOJFFKXGPKZ-UHFFFAOYSA-N 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000013014 purified material Substances 0.000 description 1
HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
230000001235 sensitizing effect Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000010414 supernatant solution Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
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
LMWUQZZRCADOGH-UHFFFAOYSA-N tert-butyl-dimethyl-pyrrolidin-1-yloxysilane Chemical compound CC(C)(C)[Si](C)(C)ON1CCCC1 LMWUQZZRCADOGH-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
210000000626 ureter Anatomy 0.000 description 1
210000003708 urethra Anatomy 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
- A61P9/06—Antiarrhythmics
- 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
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C—CHEMISTRY; METALLURGY
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Quinoline Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

APAP/P/1996/000900A 1995-12-23 1996-12-19 Quinoline and quinazoline compounds useful in therapy. AP715A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB9526546.8A GB9526546D0 (en)	1995-12-23	1995-12-23	Compounds useful in therapy

Publications (2)

Publication Number	Publication Date
AP9600900A0 AP9600900A0 (en)	1997-01-31
AP715A true AP715A (en)	1998-12-30

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ID=10786091

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1996/000900A AP715A (en)	1995-12-23	1996-12-19	Quinoline and quinazoline compounds useful in therapy.

Country Status (34)

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US (3)	US6103738A (cs)
EP (1)	EP0877734B1 (cs)
JP (1)	JP3070958B2 (cs)
KR (1)	KR19990076693A (cs)
AP (1)	AP715A (cs)
AR (1)	AR005166A1 (cs)
AT (1)	ATE194598T1 (cs)
AU (1)	AU708979B2 (cs)
BG (1)	BG102559A (cs)
BR (1)	BR9612263A (cs)
CA (1)	CA2236814C (cs)
CO (1)	CO4480106A1 (cs)
CZ (1)	CZ197698A3 (cs)
DE (1)	DE69609353T2 (cs)
DK (1)	DK0877734T3 (cs)
ES (1)	ES2151192T3 (cs)
GB (1)	GB9526546D0 (cs)
GR (1)	GR3034225T3 (cs)
HN (1)	HN1996000082A (cs)
HR (1)	HRP960616A2 (cs)
HU (1)	HUP9903560A3 (cs)
IS (1)	IS4731A (cs)
MA (1)	MA26414A1 (cs)
NO (1)	NO982913L (cs)
NZ (1)	NZ325248A (cs)
OA (1)	OA10703A (cs)
PL (1)	PL327610A1 (cs)
PT (1)	PT877734E (cs)
SK (1)	SK81698A3 (cs)
TN (1)	TNSN96161A1 (cs)
TR (1)	TR199801195T2 (cs)
WO (1)	WO1997023462A1 (cs)
YU (1)	YU68896A (cs)
ZA (1)	ZA9610784B (cs)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9526546D0 (en) *	1995-12-23	1996-02-28	Pfizer Ltd	Compounds useful in therapy
GB9700504D0 (en) *	1997-01-11	1997-02-26	Pfizer Ltd	Pharmaceutical compounds
GB9708917D0 (en) *	1997-05-01	1997-06-25	Pfizer Ltd	Compounds useful in therapy
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Also Published As

Publication number	Publication date
CO4480106A1 (es)	1997-07-09
IS4731A (is)	1998-04-29
AU1371997A (en)	1997-07-17
AU708979B2 (en)	1999-08-19
BG102559A (en)	1999-03-31
HN1996000082A (es)	1997-06-30
GB9526546D0 (en)	1996-02-28
CA2236814A1 (en)	1997-07-03
AR005166A1 (es)	1999-04-14
NO982913D0 (no)	1998-06-22
WO1997023462A1 (en)	1997-07-03
US20020049322A1 (en)	2002-04-25
GR3034225T3 (en)	2000-12-29
DE69609353T2 (de)	2000-12-07
ATE194598T1 (de)	2000-07-15
HRP960616A2 (en)	1998-06-30
HUP9903560A3 (en)	2000-07-28
ES2151192T3 (es)	2000-12-16
TR199801195T2 (xx)	1998-10-21
US6750214B2 (en)	2004-06-15
US6642242B2 (en)	2003-11-04
US6103738A (en)	2000-08-15
JP3070958B2 (ja)	2000-07-31
CZ197698A3 (cs)	1999-03-17
SK81698A3 (en)	2000-04-10
US20030220332A1 (en)	2003-11-27
DK0877734T3 (da)	2000-11-20
DE69609353D1 (de)	2000-08-17
CA2236814C (en)	2001-09-18
KR19990076693A (ko)	1999-10-15
ZA9610784B (en)	1998-06-22
PL327610A1 (en)	1998-12-21
EP0877734A1 (en)	1998-11-18
OA10703A (en)	2002-11-28
BR9612263A (pt)	1999-07-13
YU68896A (sh)	1999-07-28
AP9600900A0 (en)	1997-01-31
NO982913L (no)	1998-07-30
PT877734E (pt)	2000-12-29
JPH11501668A (ja)	1999-02-09
TNSN96161A1 (fr)	2005-03-15
NZ325248A (en)	1999-09-29
EP0877734B1 (en)	2000-07-12
MA26414A1 (fr)	2004-12-20
HUP9903560A2 (hu)	2000-05-28

Publication	Publication Date	Title
EP0877734B1 (en)	2000-07-12	Quinoline and quinazoline compounds useful in therapy
US6653302B2 (en)	2003-11-25	Quinoline and quinazoline compounds useful in therapy
US6417194B1 (en)	2002-07-09	Quinolines and quinazolines useful in therapy
US6649620B2 (en)	2003-11-18	Quinoline and quinazoline compounds useful in therapy
MXPA98005122A (en)	1999-04-06	Compounds of quinoline and quinazoline useful in tera
MXPA98003607A (en)	2000-01-01	Compounds of quinoline and quinazoline useful in tera