NO318609B1 - Kinolin- og kinazolinforbindelser nyttige i terapi, spesielt i behandlingen av benign prostatisk hyperplasi - Google Patents

Kinolin- og kinazolinforbindelser nyttige i terapi, spesielt i behandlingen av benign prostatisk hyperplasi Download PDF

Info

Publication number: NO318609B1
Authority: NO; Norway
Prior art keywords: vol; meoh; compound; product; give
Prior art date: 1997-01-11

Application number

NO19993396A

Other languages

English (en)

Norwegian (no)

Other versions

NO993396D0 (no

NO993396L (no

Inventor

David Nathan Abraham Fox

Original Assignee

Pfizer

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.)

1997-01-11

Filing date

1999-07-09

Publication date

2005-04-18

1999-07-09 Application filed by Pfizer filed Critical Pfizer

1999-07-09 Publication of NO993396D0 publication Critical patent/NO993396D0/no

1999-07-09 Publication of NO993396L publication Critical patent/NO993396L/no

2005-04-18 Publication of NO318609B1 publication Critical patent/NO318609B1/no

Links

206010004446 Benign prostatic hyperplasia Diseases 0.000 title claims description 7
208000004403 Prostatic Hyperplasia Diseases 0.000 title claims description 7
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 5
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 2
238000002560 therapeutic procedure Methods 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 318
-1 1,4-diazepan-1-yl Chemical group 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
229910052740 iodine Inorganic materials 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000002971 oxazolyl group Chemical group 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 487
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 207
239000000047 product Substances 0.000 description 143
239000000243 solution Substances 0.000 description 104
235000019439 ethyl acetate Nutrition 0.000 description 102
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
239000007787 solid Substances 0.000 description 85
238000000034 method Methods 0.000 description 84
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 82
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
230000002829 reductive effect Effects 0.000 description 80
239000000741 silica gel Substances 0.000 description 80
229910002027 silica gel Inorganic materials 0.000 description 80
239000011541 reaction mixture Substances 0.000 description 69
238000006243 chemical reaction Methods 0.000 description 67
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 56
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
239000000203 mixture Substances 0.000 description 44
239000012074 organic phase Substances 0.000 description 44
239000012043 crude product Substances 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
239000006260 foam Substances 0.000 description 29
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
239000003921 oil Substances 0.000 description 26
235000019198 oils Nutrition 0.000 description 26
239000008346 aqueous phase Substances 0.000 description 19
238000001816 cooling Methods 0.000 description 19
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 17
239000012267 brine Substances 0.000 description 16
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 16
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 16
238000010992 reflux Methods 0.000 description 16
229920006395 saturated elastomer Polymers 0.000 description 16
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
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 14
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
230000002411 adverse Effects 0.000 description 13
230000008569 process Effects 0.000 description 13
235000017557 sodium bicarbonate Nutrition 0.000 description 13
229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
238000001665 trituration Methods 0.000 description 10
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 10
239000000284 extract Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
238000007792 addition Methods 0.000 description 8
238000001914 filtration Methods 0.000 description 8
210000001519 tissue Anatomy 0.000 description 8
229910052760 oxygen Inorganic materials 0.000 description 7
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000012071 phase Substances 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
WTFFOOAJSDVASL-UHFFFAOYSA-N tributyl(pyrimidin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CC=N1 WTFFOOAJSDVASL-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
125000000623 heterocyclic group Chemical group 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000001301 oxygen Substances 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
230000004044 response Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
238000012360 testing method Methods 0.000 description 5
239000011592 zinc chloride Substances 0.000 description 5
235000005074 zinc chloride Nutrition 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical compound C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 description 4
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 4
229910021595 Copper(I) iodide Inorganic materials 0.000 description 4
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
239000003054 catalyst Substances 0.000 description 4
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000009472 formulation Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
230000000269 nucleophilic effect Effects 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000000746 purification Methods 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
238000005406 washing Methods 0.000 description 4
ZWVMLYRJXORSEP-LURJTMIESA-N (2s)-hexane-1,2,6-triol Chemical compound OCCCC[C@H](O)CO ZWVMLYRJXORSEP-LURJTMIESA-N 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 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
230000009471 action Effects 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
230000037396 body weight Effects 0.000 description 3
230000009989 contractile response Effects 0.000 description 3
239000013078 crystal Substances 0.000 description 3
230000001186 cumulative effect Effects 0.000 description 3
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000007789 gas Substances 0.000 description 3
229960000485 methotrexate Drugs 0.000 description 3
210000000056 organ Anatomy 0.000 description 3
210000002307 prostate Anatomy 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
239000011550 stock solution Substances 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
229930182836 (R)-noradrenaline Natural products 0.000 description 2
SXIYEBVAQTUBOQ-UHFFFAOYSA-N 2-(2,2,2-trifluoroacetyl)-3,4-dihydro-1h-isoquinoline-7-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=C2CN(C(=O)C(F)(F)F)CCC2=C1 SXIYEBVAQTUBOQ-UHFFFAOYSA-N 0.000 description 2
OEJOAMBYMBTZOW-UHFFFAOYSA-N 2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinoline-7-sulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC(=CC=C4CC3)S(N)(=O)=O)=NC(N)=C2C=1C1=CC=CC=N1 OEJOAMBYMBTZOW-UHFFFAOYSA-N 0.000 description 2
NFCBBVSALFZWGG-UHFFFAOYSA-N 2-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)-6,7-dimethoxy-5-pyridin-2-ylquinolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC=CN=C4CC3)=CC(N)=C2C=1C1=CC=CC=N1 NFCBBVSALFZWGG-UHFFFAOYSA-N 0.000 description 2
KAPBSPPXEFJXBS-UHFFFAOYSA-N 2-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)-6,7-dimethoxy-5-pyrimidin-2-ylquinolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC=CN=C4CC3)=CC(N)=C2C=1C1=NC=CC=N1 KAPBSPPXEFJXBS-UHFFFAOYSA-N 0.000 description 2
PWELJXSZVWUHIB-UHFFFAOYSA-N 2-iodo-3,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(I)=C1OC PWELJXSZVWUHIB-UHFFFAOYSA-N 0.000 description 2
LBKFGYZQBSGRHY-UHFFFAOYSA-N 3-hydroxy-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1O LBKFGYZQBSGRHY-UHFFFAOYSA-N 0.000 description 2
FPEAARFNXIWCTP-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1,6-naphthyridine Chemical compound C1=CC=C2CNCCC2=N1 FPEAARFNXIWCTP-UHFFFAOYSA-N 0.000 description 2
JQKSHSJYTGHWEK-UHFFFAOYSA-N 6,7-dimethoxy-2-(2-methyl-7,8-dihydro-5h-1,6-naphthyridin-6-yl)-5-pyridin-2-ylquinolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC=C(C)N=C4CC3)=CC(N)=C2C=1C1=CC=CC=N1 JQKSHSJYTGHWEK-UHFFFAOYSA-N 0.000 description 2
JCJGRGUZTUIIES-UHFFFAOYSA-N 6,7-dimethoxy-2-(5-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)-5-pyridin-2-ylquinolin-4-amine Chemical compound C1CC=2C(OC)=CC=CC=2CN1C(N=C1C=C(OC)C=2OC)=CC(N)=C1C=2C1=CC=CC=N1 JCJGRGUZTUIIES-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
244000025254 Cannabis sativa Species 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
CEIXWJHURKEBMQ-UHFFFAOYSA-N Heliamine Chemical compound C1CNCC2=C1C=C(OC)C(OC)=C2 CEIXWJHURKEBMQ-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
241001465754 Metazoa Species 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
235000019502 Orange oil Nutrition 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
229940123934 Reductase inhibitor Drugs 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
WJOJXBOIORNHIE-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxy-5-pyridin-3-ylquinazolin-2-yl)-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=NC(N)=C2C=1C1=CC=CN=C1 WJOJXBOIORNHIE-UHFFFAOYSA-N 0.000 description 2
VFQGXDBXPPSJMK-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxy-5-thiophen-3-ylquinazolin-2-yl)-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=NC(N)=C2C=1C=1C=CSC=1 VFQGXDBXPPSJMK-UHFFFAOYSA-N 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 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
239000004327 boric acid Substances 0.000 description 2
244000309464 bull Species 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
230000008859 change Effects 0.000 description 2
239000003153 chemical reaction reagent Substances 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
230000002860 competitive effect Effects 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000000375 direct analysis in real time Methods 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000012063 dual-affinity re-targeting Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
210000003191 femoral vein Anatomy 0.000 description 2
CSNXUYRHPXGSJD-UHFFFAOYSA-N isoquinolin-5-ol Chemical compound N1=CC=C2C(O)=CC=CC2=C1 CSNXUYRHPXGSJD-UHFFFAOYSA-N 0.000 description 2
HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 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
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
OLYXPBZBZBVRGD-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)=NC(N)=C2C=1C1=CC=CC=N1 OLYXPBZBZBVRGD-UHFFFAOYSA-N 0.000 description 2
LFTSWDCFDZVSMC-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-7-yl]morpholine-4-sulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC(NS(=O)(=O)N5CCOCC5)=CC=C4CC3)=NC(N)=C2C=1C1=CC=CC=N1 LFTSWDCFDZVSMC-UHFFFAOYSA-N 0.000 description 2
KYKQRIMQHMVYBI-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyrimidin-2-ylquinolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)=CC(N)=C2C=1C1=NC=CC=N1 KYKQRIMQHMVYBI-UHFFFAOYSA-N 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
150000003246 quinazolines Chemical class 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 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
239000007909 solid dosage form Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
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 2
UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
229910052718 tin Chemical class 0.000 description 2
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
HFODCIWEQMGWCT-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-7-sulfonamide;hydrochloride Chemical compound Cl.C1CNCC2=CC(S(=O)(=O)N)=CC=C21 HFODCIWEQMGWCT-UHFFFAOYSA-N 0.000 description 1
CXXJGLYULLFVJR-UHFFFAOYSA-N 1,4-diazepan-1-yl(morpholin-4-yl)methanone;hydrochloride Chemical compound Cl.C1CCNCCN1C(=O)N1CCOCC1 CXXJGLYULLFVJR-UHFFFAOYSA-N 0.000 description 1
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
YWHLVOBQBCLQDH-UHFFFAOYSA-N 1-(2-methyl-7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethanone Chemical compound CC1=CC=C2CN(C(=O)C)CCC2=N1 YWHLVOBQBCLQDH-UHFFFAOYSA-N 0.000 description 1
IJRSUVXSVJEXFY-UHFFFAOYSA-N 1-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethanone Chemical compound C1=CC=C2CN(C(=O)C)CCC2=N1 IJRSUVXSVJEXFY-UHFFFAOYSA-N 0.000 description 1
SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
AFWHVAFMAIDVTH-UHFFFAOYSA-N 1-methoxyisoquinoline Chemical compound C1=CC=C2C(OC)=NC=CC2=C1 AFWHVAFMAIDVTH-UHFFFAOYSA-N 0.000 description 1
RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 1
NOVIRODZMIZUPA-UHFFFAOYSA-N 2,3-dihydro-1h-isoindole;hydrochloride Chemical compound Cl.C1=CC=C2CNCC2=C1 NOVIRODZMIZUPA-UHFFFAOYSA-N 0.000 description 1
RBPYSBZQDGHCTB-UHFFFAOYSA-N 2-(1,3-dihydroisoindol-2-yl)-6,7-dimethoxy-5-pyridin-2-ylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC=CC=C4C3)=NC(N)=C2C=1C1=CC=CC=N1 RBPYSBZQDGHCTB-UHFFFAOYSA-N 0.000 description 1
UAISNJSAZMHJSZ-UHFFFAOYSA-N 2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)-5-iodo-6,7-dimethoxyquinolin-4-amine Chemical compound IC1=C(OC)C(OC)=CC2=NC(N3CCC=4C=C(C(=CC=4C3)OC)OC)=CC(N)=C21 UAISNJSAZMHJSZ-UHFFFAOYSA-N 0.000 description 1
RMRBAJLPYPRPLZ-UHFFFAOYSA-N 2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)-6,7-dimethoxy-5-pyridin-2-ylquinolin-4-amine Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(N=C1C=C(OC)C=2OC)=CC(N)=C1C=2C1=CC=CC=N1 RMRBAJLPYPRPLZ-UHFFFAOYSA-N 0.000 description 1
QSVSMEJQKHDZAA-UHFFFAOYSA-N 2-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)-6,7-dimethoxy-5-pyrimidin-2-ylquinolin-4-amine Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(N=C1C=C(OC)C=2OC)=CC(N)=C1C=2C1=NC=CC=N1 QSVSMEJQKHDZAA-UHFFFAOYSA-N 0.000 description 1
RXSFXUUMHHFKAL-UHFFFAOYSA-N 2-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)-6,7-dimethoxy-5-pyridin-2-ylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC=CN=C4CC3)=NC(N)=C2C=1C1=CC=CC=N1 RXSFXUUMHHFKAL-UHFFFAOYSA-N 0.000 description 1
UTOWYSASYDVMCN-UHFFFAOYSA-N 2-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)-6,7-dimethoxy-5-pyrimidin-2-ylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC=CN=C4CC3)=NC(N)=C2C=1C1=NC=CC=N1 UTOWYSASYDVMCN-UHFFFAOYSA-N 0.000 description 1
STXKXERUAKXEDI-UHFFFAOYSA-N 2-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)-7-methoxy-5-pyrimidin-2-yl-6-(2,2,2-trifluoroethoxy)quinolin-4-amine Chemical compound FC(F)(F)COC=1C(OC)=CC2=NC(N3CC4=CC=CN=C4CC3)=CC(N)=C2C=1C1=NC=CC=N1 STXKXERUAKXEDI-UHFFFAOYSA-N 0.000 description 1
CQDMQOQCJRLUQN-UHFFFAOYSA-N 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine Chemical compound C1NCCC2=NC(Cl)=CC=C21 CQDMQOQCJRLUQN-UHFFFAOYSA-N 0.000 description 1
FRFOPAQLAUHXAL-UHFFFAOYSA-N 2-chloro-5-iodo-6,7-dimethoxyquinazolin-4-amine Chemical compound ClC1=NC(N)=C2C(I)=C(OC)C(OC)=CC2=N1 FRFOPAQLAUHXAL-UHFFFAOYSA-N 0.000 description 1
KBYIDEJTWRHSAX-UHFFFAOYSA-N 2-chloro-6,7-dimethoxy-5-pyridin-2-ylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(Cl)=NC(N)=C2C=1C1=CC=CC=N1 KBYIDEJTWRHSAX-UHFFFAOYSA-N 0.000 description 1
XKMXPSYZZLWUBZ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxy-5-thiophen-3-ylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(Cl)=NC(N)=C2C=1C=1C=CSC=1 XKMXPSYZZLWUBZ-UHFFFAOYSA-N 0.000 description 1
HPNXLCZBUFZKMX-UHFFFAOYSA-N 2-iodo-3,4-dimethoxy-6-[1-(2-methyl-7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethylideneamino]benzonitrile Chemical compound IC1=C(OC)C(OC)=CC(N=C(C)N2CC3=CC=C(C)N=C3CC2)=C1C#N HPNXLCZBUFZKMX-UHFFFAOYSA-N 0.000 description 1
FFFLIDIKMPYWGQ-UHFFFAOYSA-N 2-iodo-3,4-dimethoxy-6-[1-(5-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)ethylideneamino]benzonitrile Chemical compound C1CC=2C(OC)=CC=CC=2CN1C(C)=NC1=CC(OC)=C(OC)C(I)=C1C#N FFFLIDIKMPYWGQ-UHFFFAOYSA-N 0.000 description 1
RXTNFUDZKNTLJF-UHFFFAOYSA-N 2-iodo-3,4-dimethoxy-6-[1-[4-(morpholine-4-carbonyl)-1,4-diazepan-1-yl]ethylideneamino]benzonitrile Chemical compound IC1=C(OC)C(OC)=CC(N=C(C)N2CCN(CCC2)C(=O)N2CCOCC2)=C1C#N RXTNFUDZKNTLJF-UHFFFAOYSA-N 0.000 description 1
KLYJJSPLEPRPKW-UHFFFAOYSA-N 2-iodo-3,4-dimethoxy-6-nitrobenzoic acid Chemical compound COC1=CC([N+]([O-])=O)=C(C(O)=O)C(I)=C1OC KLYJJSPLEPRPKW-UHFFFAOYSA-N 0.000 description 1
ROAHGYIWORDPKO-UHFFFAOYSA-N 2-iodo-3,4-dimethoxy-6-nitrobenzonitrile Chemical compound COC1=CC([N+]([O-])=O)=C(C#N)C(I)=C1OC ROAHGYIWORDPKO-UHFFFAOYSA-N 0.000 description 1
JTVXKTKBFZQQPX-UHFFFAOYSA-N 2-iodo-3,4-dimethoxybenzonitrile Chemical compound COC1=CC=C(C#N)C(I)=C1OC JTVXKTKBFZQQPX-UHFFFAOYSA-N 0.000 description 1
YIPNABRAPURHFP-UHFFFAOYSA-N 2-iodo-4-methoxy-3-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound COC1=CC=C(C#N)C(I)=C1OCC(F)(F)F YIPNABRAPURHFP-UHFFFAOYSA-N 0.000 description 1
KTCBMTQLVIHSHH-UHFFFAOYSA-N 2-iodo-4-methoxy-6-nitro-3-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound COC1=CC([N+]([O-])=O)=C(C#N)C(I)=C1OCC(F)(F)F KTCBMTQLVIHSHH-UHFFFAOYSA-N 0.000 description 1
WZQRYUYBDJIRBR-UHFFFAOYSA-N 2-methyl-5,6,7,8-tetrahydro-1,6-naphthyridine Chemical compound C1NCCC2=NC(C)=CC=C21 WZQRYUYBDJIRBR-UHFFFAOYSA-N 0.000 description 1
ORJSIFYUPXLPLK-UHFFFAOYSA-N 2-methyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine;hydrochloride Chemical compound Cl.C1NCCC2=NC(C)=NC=C21 ORJSIFYUPXLPLK-UHFFFAOYSA-N 0.000 description 1
RTBMQNOWHTWQDX-UHFFFAOYSA-N 3,4-dimethoxy-6-[1-(2-methyl-7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethylideneamino]-2-pyridin-2-ylbenzonitrile Chemical compound COC=1C(OC)=CC(N=C(C)N2CC3=CC=C(C)N=C3CC2)=C(C#N)C=1C1=CC=CC=N1 RTBMQNOWHTWQDX-UHFFFAOYSA-N 0.000 description 1
DAUAQNGYDSHRET-UHFFFAOYSA-N 3,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1OC DAUAQNGYDSHRET-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
SOIUNFGITAXPDJ-UHFFFAOYSA-N 3-ethoxy-2-iodo-4-methoxy-6-nitrobenzonitrile Chemical compound CCOC1=C(I)C(C#N)=C([N+]([O-])=O)C=C1OC SOIUNFGITAXPDJ-UHFFFAOYSA-N 0.000 description 1
IHJATCRRPOSYQS-UHFFFAOYSA-N 3h-3-benzazepine;hydrochloride Chemical compound Cl.C1=CNC=CC2=CC=CC=C21 IHJATCRRPOSYQS-UHFFFAOYSA-N 0.000 description 1
FKTYRSHBZBEHNA-UHFFFAOYSA-N 4-amino-5-iodo-6,7-dimethoxy-1h-quinazolin-2-one Chemical compound OC1=NC(N)=C2C(I)=C(OC)C(OC)=CC2=N1 FKTYRSHBZBEHNA-UHFFFAOYSA-N 0.000 description 1
HCSPGYISMLEBLZ-UHFFFAOYSA-N 4-methoxy-3-(2,2,2-trifluoroethoxy)benzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1OCC(F)(F)F HCSPGYISMLEBLZ-UHFFFAOYSA-N 0.000 description 1
YXMOQYGYWUTHHS-UHFFFAOYSA-N 4-methoxy-6-[1-[4-(morpholine-4-carbonyl)-1,4-diazepan-1-yl]ethylideneamino]-2-pyridin-2-yl-3-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound N#CC=1C(C=2N=CC=CC=2)=C(OCC(F)(F)F)C(OC)=CC=1N=C(C)N(CC1)CCCN1C(=O)N1CCOCC1 YXMOQYGYWUTHHS-UHFFFAOYSA-N 0.000 description 1
DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical compound N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 description 1
DUOAMFNJOVGYLY-UHFFFAOYSA-N 5-iodo-6,7-dimethoxy-1h-quinazoline-2,4-dione Chemical compound OC1=NC(O)=C2C(I)=C(OC)C(OC)=CC2=N1 DUOAMFNJOVGYLY-UHFFFAOYSA-N 0.000 description 1
MCJYXDLWQYGCIQ-UHFFFAOYSA-N 5-methoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=C1C=CC=C2OC MCJYXDLWQYGCIQ-UHFFFAOYSA-N 0.000 description 1
XPJAFCWEOPGODF-UHFFFAOYSA-N 6,7-dimethoxy-2-(7-piperazin-1-ylsulfonyl-3,4-dihydro-1h-isoquinolin-2-yl)-5-pyridin-2-ylquinazolin-4-amine Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC(=CC=C4CC3)S(=O)(=O)N3CCNCC3)=NC(N)=C2C=1C1=CC=CC=N1 XPJAFCWEOPGODF-UHFFFAOYSA-N 0.000 description 1
RXTXVHONZWEDDZ-UHFFFAOYSA-N 6,7-dimethoxy-2-(7-piperazin-1-ylsulfonyl-3,4-dihydro-1h-isoquinolin-2-yl)-5-pyridin-2-ylquinazolin-4-amine;trihydrochloride Chemical compound Cl.Cl.Cl.COC=1C(OC)=CC2=NC(N3CC4=CC(=CC=C4CC3)S(=O)(=O)N3CCNCC3)=NC(N)=C2C=1C1=CC=CC=N1 RXTXVHONZWEDDZ-UHFFFAOYSA-N 0.000 description 1
AIJSTPCYBXTVRV-UHFFFAOYSA-N 6,7-dimethoxy-5-thiophen-3-yl-1h-quinazoline-2,4-dione Chemical compound COC=1C(OC)=CC2=NC(O)=NC(O)=C2C=1C=1C=CSC=1 AIJSTPCYBXTVRV-UHFFFAOYSA-N 0.000 description 1
TVWCMZDNPBGGGY-UHFFFAOYSA-N 6-[1-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethylideneamino]-2-iodo-3,4-dimethoxybenzonitrile Chemical compound IC1=C(OC)C(OC)=CC(N=C(C)N2CC3=CC=CN=C3CC2)=C1C#N TVWCMZDNPBGGGY-UHFFFAOYSA-N 0.000 description 1
WKWXEPSIHPRTRP-UHFFFAOYSA-N 6-[1-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethylideneamino]-2-iodo-4-methoxy-3-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound IC1=C(OCC(F)(F)F)C(OC)=CC(N=C(C)N2CC3=CC=CN=C3CC2)=C1C#N WKWXEPSIHPRTRP-UHFFFAOYSA-N 0.000 description 1
PZQNDFJURNJNFV-UHFFFAOYSA-N 6-[1-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethylideneamino]-3,4-dimethoxy-2-pyridin-2-ylbenzonitrile Chemical compound COC=1C(OC)=CC(N=C(C)N2CC3=CC=CN=C3CC2)=C(C#N)C=1C1=CC=CC=N1 PZQNDFJURNJNFV-UHFFFAOYSA-N 0.000 description 1
QFDIHAUWYQCDQC-UHFFFAOYSA-N 6-[1-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethylideneamino]-3,4-dimethoxy-2-pyrimidin-2-ylbenzonitrile Chemical compound COC=1C(OC)=CC(N=C(C)N2CC3=CC=CN=C3CC2)=C(C#N)C=1C1=NC=CC=N1 QFDIHAUWYQCDQC-UHFFFAOYSA-N 0.000 description 1
XVMGLBXNUNRPST-UHFFFAOYSA-N 6-[1-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)ethylideneamino]-4-methoxy-2-pyrimidin-2-yl-3-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound FC(F)(F)COC=1C(OC)=CC(N=C(C)N2CC3=CC=CN=C3CC2)=C(C#N)C=1C1=NC=CC=N1 XVMGLBXNUNRPST-UHFFFAOYSA-N 0.000 description 1
KKQRWFUZTJBFEX-UHFFFAOYSA-N 6-amino-2-iodo-3,4-dimethoxybenzoic acid Chemical compound COC1=CC(N)=C(C(O)=O)C(I)=C1OC KKQRWFUZTJBFEX-UHFFFAOYSA-N 0.000 description 1
LFSYMBZTFIVRSE-UHFFFAOYSA-N 6-amino-2-iodo-3,4-dimethoxybenzonitrile Chemical compound COC1=CC(N)=C(C#N)C(I)=C1OC LFSYMBZTFIVRSE-UHFFFAOYSA-N 0.000 description 1
GHESWFDTJIYIGG-UHFFFAOYSA-N 6-amino-2-iodo-4-methoxy-3-(2,2,2-trifluoroethoxy)benzonitrile Chemical compound COC1=CC(N)=C(C#N)C(I)=C1OCC(F)(F)F GHESWFDTJIYIGG-UHFFFAOYSA-N 0.000 description 1
KSLNBPVLLJOPPQ-UHFFFAOYSA-N 6-amino-3-ethoxy-2-iodo-4-methoxybenzonitrile Chemical compound CCOC1=C(I)C(C#N)=C(N)C=C1OC KSLNBPVLLJOPPQ-UHFFFAOYSA-N 0.000 description 1
VORCFXXVVSBBTM-UHFFFAOYSA-N 6-benzhydryl-2-chloro-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1CC2=NC(Cl)=CC=C2CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 VORCFXXVVSBBTM-UHFFFAOYSA-N 0.000 description 1
SZWKETFREPZUDD-UHFFFAOYSA-N 6-benzyl-1,3,4,5,7,8-hexahydro-1,6-naphthyridin-2-one Chemical compound N1C(=O)CCC(C2)=C1CCN2CC1=CC=CC=C1 SZWKETFREPZUDD-UHFFFAOYSA-N 0.000 description 1
BPAUBEUYIXYWAV-UHFFFAOYSA-N 6-benzyl-2-chloro-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1CC2=NC(Cl)=CC=C2CN1CC1=CC=CC=C1 BPAUBEUYIXYWAV-UHFFFAOYSA-N 0.000 description 1
GFFYNOLYZYYAIA-UHFFFAOYSA-N 7-trityl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine Chemical compound C1CC2=CN=CN=C2CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 GFFYNOLYZYYAIA-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
XDMFJGLXMGEGPU-STBIYBPSSA-N C1CC=2C(OC)=CC=CC=2CN1C(\C)=N\C(C=1C#N)=CC(OC)=C(OC)C=1C1=CC=CC=N1 Chemical compound C1CC=2C(OC)=CC=CC=2CN1C(\C)=N\C(C=1C#N)=CC(OC)=C(OC)C=1C1=CC=CC=N1 XDMFJGLXMGEGPU-STBIYBPSSA-N 0.000 description 1
FTWGZTXKFAOYGC-UXHLAJHPSA-N CCOC1=C(OC)C=C(\N=C(/C)N2CC3=C(C(=CC=C3)NS(C)(=O)=O)CC2)C(C#N)=C1C1=CC=CC=N1 Chemical compound CCOC1=C(OC)C=C(\N=C(/C)N2CC3=C(C(=CC=C3)NS(C)(=O)=O)CC2)C(C#N)=C1C1=CC=CC=N1 FTWGZTXKFAOYGC-UXHLAJHPSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
208000010228 Erectile Dysfunction Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
208000031226 Hyperlipidaemia Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
WJAJPNHVVFWKKL-UHFFFAOYSA-N Methoxamine Chemical compound COC1=CC=C(OC)C(C(O)C(C)N)=C1 WJAJPNHVVFWKKL-UHFFFAOYSA-N 0.000 description 1
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
NUQYMXWFCUXDDT-UHFFFAOYSA-N N-quinolin-5-ylmethanesulfonamide Chemical compound C1=CC=C2C(NS(=O)(=O)C)=CC=CC2=N1 NUQYMXWFCUXDDT-UHFFFAOYSA-N 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229910019213 POCl3 Inorganic materials 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
206010070834 Sensitisation Diseases 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
229910052770 Uranium Inorganic materials 0.000 description 1
GPVDHNVGGIAOQT-UHFFFAOYSA-N Veratric acid Natural products COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
OKNOASKSKHKTME-UHFFFAOYSA-N [4-(4-amino-5-iodo-6,7-dimethoxyquinazolin-2-yl)-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound N=1C(N)=C2C(I)=C(OC)C(OC)=CC2=NC=1N(CC1)CCCN1C(=O)N1CCOCC1 OKNOASKSKHKTME-UHFFFAOYSA-N 0.000 description 1
CMBPHJUXDXPUCR-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=NC(N)=C2C=1C1=CC=CC=N1 CMBPHJUXDXPUCR-UHFFFAOYSA-N 0.000 description 1
SIEZMKFCWOZNLH-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinolin-2-yl)-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=CC(N)=C2C=1C1=CC=CC=N1 SIEZMKFCWOZNLH-UHFFFAOYSA-N 0.000 description 1
JBLDPUDNYNVDFO-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxy-5-thiophen-2-ylquinolin-2-yl)-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=CC(N)=C2C=1C1=CC=CS1 JBLDPUDNYNVDFO-UHFFFAOYSA-N 0.000 description 1
SIHIQSOUYQGVOI-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxy-5-thiophen-3-ylquinolin-2-yl)-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=CC(N)=C2C=1C=1C=CSC=1 SIHIQSOUYQGVOI-UHFFFAOYSA-N 0.000 description 1
IRPJMQAXJJCXNX-UHFFFAOYSA-N [4-[4-amino-5-(furan-2-yl)-6,7-dimethoxyquinolin-2-yl]-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=CC(N)=C2C=1C1=CC=CO1 IRPJMQAXJJCXNX-UHFFFAOYSA-N 0.000 description 1
UQWGPRNGAXDRQE-UHFFFAOYSA-N [4-[4-amino-5-(furan-3-yl)-6,7-dimethoxyquinolin-2-yl]-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=CC(N)=C2C=1C=1C=COC=1 UQWGPRNGAXDRQE-UHFFFAOYSA-N 0.000 description 1
PWHDGYLJKZMWQU-UHFFFAOYSA-N [4-[4-amino-6,7-dimethoxy-5-(1,3-oxazol-2-yl)quinolin-2-yl]-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=CC(N)=C2C=1C1=NC=CO1 PWHDGYLJKZMWQU-UHFFFAOYSA-N 0.000 description 1
GHNMDDCBHQRIGX-UHFFFAOYSA-N [4-[4-amino-7-methoxy-5-pyridin-2-yl-6-(2,2,2-trifluoroethoxy)quinolin-2-yl]-1,4-diazepan-1-yl]-morpholin-4-ylmethanone Chemical compound FC(F)(F)COC=1C(OC)=CC2=NC(N3CCN(CCC3)C(=O)N3CCOCC3)=CC(N)=C2C=1C1=CC=CC=N1 GHNMDDCBHQRIGX-UHFFFAOYSA-N 0.000 description 1
ZDVDCDLBOLSVGM-UHFFFAOYSA-N [chloro(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(Cl)C1=CC=CC=C1 ZDVDCDLBOLSVGM-UHFFFAOYSA-N 0.000 description 1
XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
239000000556 agonist Substances 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
230000008485 antagonism Effects 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
210000002376 aorta thoracic Anatomy 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000036760 body temperature Effects 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
150000001638 boron Chemical class 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
125000001626 borono group Chemical group [H]OB([*])O[H] 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229960003920 cocaine Drugs 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
238000010276 construction Methods 0.000 description 1
230000008602 contraction Effects 0.000 description 1
230000001595 contractor effect Effects 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
150000001923 cyclic compounds Chemical class 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
OJKBCQOJVMAHDX-UHFFFAOYSA-N diethyl(pyridin-3-yl)borane Chemical compound CCB(CC)C1=CC=CN=C1 OJKBCQOJVMAHDX-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000011833 dog model Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
210000000981 epithelium Anatomy 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
239000012054 flavored emulsion Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
230000027119 gastric acid secretion Effects 0.000 description 1
239000008103 glucose Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
201000001881 impotence Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000002350 laparotomy Methods 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229960005192 methoxamine Drugs 0.000 description 1
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 1
YDJRHNKOVNTVTL-UHFFFAOYSA-N methyl 4-methoxy-3-(2,2,2-trifluoroethoxy)benzoate Chemical compound COC(=O)C1=CC=C(OC)C(OCC(F)(F)F)=C1 YDJRHNKOVNTVTL-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
VIXRVBRUSDQWJD-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-5-yl)methanesulfonamide;hydrochloride Chemical compound Cl.C1NCCC2=C1C=CC=C2NS(=O)(=O)C VIXRVBRUSDQWJD-UHFFFAOYSA-N 0.000 description 1
OINVTXITOIBAOF-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-7-yl)morpholine-4-sulfonamide Chemical compound C=1C=C2CCNCC2=CC=1NS(=O)(=O)N1CCOCC1 OINVTXITOIBAOF-UHFFFAOYSA-N 0.000 description 1
WQAGJECWVGDANY-UHFFFAOYSA-N n-(2-acetyl-3,4-dihydro-1h-isoquinolin-5-yl)methanesulfonamide Chemical compound C1=CC=C(NS(C)(=O)=O)C2=C1CN(C(=O)C)CC2 WQAGJECWVGDANY-UHFFFAOYSA-N 0.000 description 1
OGEJUEKBJWVDGO-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide;hydrochloride Chemical compound Cl.COC=1C(OC)=CC2=NC(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)=CC(N)=C2C=1C1=CC=CC=N1 OGEJUEKBJWVDGO-UHFFFAOYSA-N 0.000 description 1
UOHFXMCVBVOFJF-UHFFFAOYSA-N n-[2-(4-amino-6-ethoxy-7-methoxy-5-pyridin-2-ylquinolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound CCOC1=C(OC)C=C2N=C(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)C=C(N)C2=C1C1=CC=CC=N1 UOHFXMCVBVOFJF-UHFFFAOYSA-N 0.000 description 1
RWWTXLPXVASJDM-UHFFFAOYSA-N n-[2-[n-(2-cyano-3-iodo-4,5-dimethoxyphenyl)-c-methylcarbonimidoyl]-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound IC1=C(OC)C(OC)=CC(N=C(C)N2CC3=C(C(=CC=C3)NS(C)(=O)=O)CC2)=C1C#N RWWTXLPXVASJDM-UHFFFAOYSA-N 0.000 description 1
HFHWJPPXFDPZKE-UHFFFAOYSA-N n-[2-[n-(2-cyano-4,5-dimethoxy-3-pyrimidin-2-ylphenyl)-c-methylcarbonimidoyl]-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound COC=1C(OC)=CC(N=C(C)N2CC3=C(C(=CC=C3)NS(C)(=O)=O)CC2)=C(C#N)C=1C1=NC=CC=N1 HFHWJPPXFDPZKE-UHFFFAOYSA-N 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
229910000069 nitrogen hydride 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
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet 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
230000002572 peristaltic 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
VRJHQPZVIGNGMX-UHFFFAOYSA-N piperidine-4-one Natural products O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
238000007790 scraping Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
230000008313 sensitization 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
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
230000003068 static effect Effects 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000010414 supernatant solution Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
WDPWEXWMQDRXAL-UHFFFAOYSA-N tert-butyl 1,4-diazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCNCC1 WDPWEXWMQDRXAL-UHFFFAOYSA-N 0.000 description 1
CWQHKGSNPFVPJN-UHFFFAOYSA-N tert-butyl 4-(1,2,3,4-tetrahydroisoquinolin-7-ylsulfonyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)C1=CC=C(CCNC2)C2=C1 CWQHKGSNPFVPJN-UHFFFAOYSA-N 0.000 description 1
RKEKDCDFCAEABK-UHFFFAOYSA-N tert-butyl 4-(morpholine-4-carbonyl)-1,4-diazepane-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCCN1C(=O)N1CCOCC1 RKEKDCDFCAEABK-UHFFFAOYSA-N 0.000 description 1
RVDSVNBBJMUXOY-UHFFFAOYSA-N tert-butyl 4-[[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-7-yl]sulfonyl]piperazine-1-carboxylate Chemical compound COC=1C(OC)=CC2=NC(N3CC4=CC(=CC=C4CC3)S(=O)(=O)N3CCN(CC3)C(=O)OC(C)(C)C)=NC(N)=C2C=1C1=CC=CC=N1 RVDSVNBBJMUXOY-UHFFFAOYSA-N 0.000 description 1
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
MQAYPFVXSPHGJM-UHFFFAOYSA-M trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=CC=CC=C1 MQAYPFVXSPHGJM-UHFFFAOYSA-M 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
239000003981 vehicle Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Chemical class 0.000 description 1
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1

Classifications

- 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
- 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
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- 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
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- 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
- C07D401/14—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 three or more hetero rings
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Urology & Nephrology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

NO19993396A 1997-01-11 1999-07-09 Kinolin- og kinazolinforbindelser nyttige i terapi, spesielt i behandlingen av benign prostatisk hyperplasi NO318609B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9700504.5A GB9700504D0 (en)	1997-01-11	1997-01-11	Pharmaceutical compounds
PCT/EP1998/000143 WO1998030560A1 (fr)	1997-01-11	1998-01-06	Composes de quinoleine et de quinazoline presentant une utilite therapeutique en particulier pour le traitement de l'hyperplasie prostatique benigne

Publications (3)

Publication Number	Publication Date
NO993396D0 NO993396D0 (no)	1999-07-09
NO993396L NO993396L (no)	1999-07-09
NO318609B1 true NO318609B1 (no)	2005-04-18

Family

ID=10805838

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19993396A NO318609B1 (no)	1997-01-11	1999-07-09	Kinolin- og kinazolinforbindelser nyttige i terapi, spesielt i behandlingen av benign prostatisk hyperplasi

Country Status (45)

Country	Link
US (4)	US6169093B1 (fr)
EP (1)	EP0968208B1 (fr)
JP (1)	JP3357677B2 (fr)
KR (1)	KR100347472B1 (fr)
CN (2)	CN1191249C (fr)
AP (1)	AP819A (fr)
AR (1)	AR010396A1 (fr)
AT (1)	ATE242238T1 (fr)
AU (1)	AU724990B2 (fr)
BG (1)	BG63918B1 (fr)
BR (1)	BR9807068A (fr)
CA (1)	CA2277473C (fr)
CZ (1)	CZ295580B6 (fr)
DE (1)	DE69815313T2 (fr)
DK (1)	DK0968208T3 (fr)
DZ (1)	DZ2394A1 (fr)
EA (1)	EA002851B1 (fr)
ES (1)	ES2198695T3 (fr)
GB (1)	GB9700504D0 (fr)
HK (1)	HK1054389B (fr)
HN (1)	HN1998000002A (fr)
HR (1)	HRP980010B1 (fr)
HU (1)	HUP0000942A3 (fr)
ID (1)	ID21863A (fr)
IL (1)	IL130762A (fr)
IS (1)	IS2012B (fr)
MA (1)	MA26465A1 (fr)
MY (1)	MY119623A (fr)
NO (1)	NO318609B1 (fr)
NZ (1)	NZ336302A (fr)
OA (1)	OA11074A (fr)
PA (1)	PA8444301A1 (fr)
PE (1)	PE44499A1 (fr)
PL (1)	PL334678A1 (fr)
PT (1)	PT968208E (fr)
SA (1)	SA97180705B1 (fr)
SI (1)	SI0968208T1 (fr)
SK (1)	SK284779B6 (fr)
TN (1)	TNSN98004A1 (fr)
TR (1)	TR199901604T2 (fr)
TW (1)	TW444013B (fr)
UA (1)	UA62945C2 (fr)
WO (1)	WO1998030560A1 (fr)
YU (1)	YU31699A (fr)
ZA (1)	ZA98166B (fr)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
IL141235A (en) *	2000-02-09	2012-04-30	Novartis Int Pharm Ltd	Combined use of an alpha-adrenoceptor antagonist and a muscarinic antagonist in the preparation of a drug for the treatment of non-malignant prostatic hyperplasia
IL150634A0 (en) *	2000-03-03	2003-02-12	Pfizer	4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline mesylate and polymorphs
EP1315714B1 (fr)	2000-08-31	2005-11-09	F. Hoffmann-La Roche Ag	Derives de la quinazoline comme antagonistes adrenergiques alpha-1
WO2002053558A1 (fr) *	2001-01-02	2002-07-11	F.Hoffman-La Roche Ag	Derives quinazolone antagonistes de recepteur alpha 1a/b adrenergique
US6900220B2 (en)	2001-01-02	2005-05-31	Syntex (U.S.A.) Llc	Quinazolone derivatives as alpha 1A/B adrenergic receptor antagonists
US6734303B2 (en)	2001-05-18	2004-05-11	Pfizer Inc.	Process for the production of quinazolines
GB0112061D0 (en) *	2001-05-18	2001-07-11	Pfizer Ltd	Process for the production of quinazolines
GB0118752D0 (en) *	2001-08-01	2001-09-26	Pfizer Ltd	Process for the production of quinazolines
US7163696B2 (en)	2001-10-11	2007-01-16	Pfizer Inc.	Pharmaceutical formulations
GB0124455D0 (en) *	2001-10-11	2001-12-05	Pfizer Ltd	Pharmaceutical formulations
GB0206033D0 (en)	2002-03-14	2002-04-24	Pfizer Ltd	Compounds useful in therapy
US7576074B2 (en)	2002-07-15	2009-08-18	Rice Kenneth D	Receptor-type kinase modulators and methods of use
GB0219961D0 (en)	2002-08-28	2002-10-02	Pfizer Ltd	Oxytocin inhibitors
GB0221579D0 (en) *	2002-09-17	2002-10-23	Pfizer Ltd	Combinations of atorvastatin and, adrenergic receptor antagonists
GB0221582D0 (en) *	2002-09-17	2002-10-23	Pfizer Ltd	Method of treatment
EP1556381B1 (fr)	2002-09-26	2008-02-20	Pfizer Limited	Pyrazole amides destines au traitement d'infections par le vih
GB0225908D0 (en) *	2002-11-06	2002-12-11	Pfizer Ltd	Treatment of female sexual dysfunction
AU2003303041B2 (en)	2002-12-13	2008-07-24	Warner-Lambert Company Llc	Alpha-2-delta ligand to treat lower urinary tract symptoms
CA2530450A1 (fr) *	2003-07-02	2005-01-20	F. Hoffmann-La Roche Ag	Derives de quinazolinone substitues en position 5
US7291640B2 (en)	2003-09-22	2007-11-06	Pfizer Inc.	Substituted triazole derivatives as oxytocin antagonists
EP2210607B1 (fr) *	2003-09-26	2011-08-17	Exelixis Inc.	N-[3-fluoro-4-({6-(méthyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phényl]-N'-(4-fluorophényl)cyclopropane-1,1-dicarboxamide pour le traitement du cancer
KR20050092519A (ko) *	2004-03-16	2005-09-22	화이자 인코포레이티드	아토르바스타틴 및 α1-아드레날린성 수용체 길항제의 조합
WO2005089804A2 (fr) *	2004-03-16	2005-09-29	Pfizer Limited	Combinaisons d'inhibiteurs de la reductase hmg-coa et d'antagonistes du recepteur adrenergique $g(a)1
JP4185154B2 (ja)	2004-04-30	2008-11-26	ワーナー−ランバートカンパニーリミテッドライアビリティーカンパニー	中枢神経系障害治療用の置換モルホリン化合物
WO2008084493A2 (fr) *	2007-01-09	2008-07-17	Unichem Laboratories Limited	Nouveau procédé de préparation de 2-halo-4-aminoquinazolines
JP2009126785A (ja) *	2007-11-19	2009-06-11	Mitsubishi Gas Chem Co Inc	２−ヨード−３，４−ジメトキシベンゾニトリルの製造方法
JP2009126784A (ja) *	2007-11-19	2009-06-11	Mitsubishi Gas Chem Co Inc	２−ヨード−３，４−ジメトキシベンゾニトリルの製造方法。
NZ779754A (en)	2009-01-16	2023-04-28	Exelixis Inc	Malate salt of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl] oxy} phenyl)-n’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer
UA108618C2 (uk)	2009-08-07	2015-05-25		Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку
SG11201607973XA (en) *	2014-03-24	2016-11-29	Guangdong Zhongsheng Pharmaceutical Co Ltd	Quinoline derivatives as smo inhibitors

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US875506A (en) *	1907-03-19	1907-12-31	Berry H Collins	Guiding attachment for penholders.
GB1390014A (en) *	1971-05-07	1975-04-09	Koninklijke Pharma Fab Nv	Process for the preparation of carbocyclic fused pyrimidine derivatives
US4026894A (en) *	1975-10-14	1977-05-31	Abbott Laboratories	Antihypertensive agents
US4098788A (en) *	1977-06-20	1978-07-04	Bristol-Myers Company	Process for preparing quinazolines
GR79603B (fr) *	1982-07-24	1984-10-31	Pfizer
GB8506174D0 (en) *	1985-03-09	1985-04-11	Pfizer Ltd	4-amino-6 7-dimethoxy-2-piperazin-1-ylquinazoline derivatives
IT1270993B (it) *	1994-03-18	1997-05-26	Recordati Chem Pharm	Derivati chinzolilamminici attivi come alfa-antagonisti
NZ325248A (en)	1995-12-23	1999-09-29	Pfizer Res & Dev	Quinoline and quinazoline 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
GB9711650D0 (en)	1997-06-05	1997-07-30	Pfizer Ltd	Compounds useful in therapy

1997
- 1997-01-11 GB GBGB9700504.5A patent/GB9700504D0/en active Pending
- 1997-11-18 TW TW086117203A patent/TW444013B/zh not_active IP Right Cessation
- 1997-12-13 SA SA97180705A patent/SA97180705B1/ar unknown
1998
- 1998-01-05 HN HN1998000002A patent/HN1998000002A/es unknown
- 1998-01-05 PE PE1998000006A patent/PE44499A1/es not_active Application Discontinuation
- 1998-01-06 WO PCT/EP1998/000143 patent/WO1998030560A1/fr not_active Ceased
- 1998-01-06 PT PT98904058T patent/PT968208E/pt unknown
- 1998-01-06 BR BR9807068-1A patent/BR9807068A/pt not_active Application Discontinuation
- 1998-01-06 ES ES98904058T patent/ES2198695T3/es not_active Expired - Lifetime
- 1998-01-06 AT AT98904058T patent/ATE242238T1/de not_active IP Right Cessation
- 1998-01-06 DK DK98904058T patent/DK0968208T3/da active
- 1998-01-06 PL PL98334678A patent/PL334678A1/xx unknown
- 1998-01-06 YU YU31699A patent/YU31699A/sh unknown
- 1998-01-06 NZ NZ336302A patent/NZ336302A/xx unknown
- 1998-01-06 ID IDW990660A patent/ID21863A/id unknown
- 1998-01-06 CA CA002277473A patent/CA2277473C/fr not_active Expired - Fee Related
- 1998-01-06 SI SI9830477T patent/SI0968208T1/xx unknown
- 1998-01-06 PA PA19988444301A patent/PA8444301A1/es unknown
- 1998-01-06 HU HU0000942A patent/HUP0000942A3/hu unknown
- 1998-01-06 JP JP53056598A patent/JP3357677B2/ja not_active Expired - Lifetime
- 1998-01-06 TR TR1999/01604T patent/TR199901604T2/xx unknown
- 1998-01-06 US US09/341,228 patent/US6169093B1/en not_active Expired - Lifetime
- 1998-01-06 CN CNB011432918A patent/CN1191249C/zh not_active Expired - Fee Related
- 1998-01-06 EP EP98904058A patent/EP0968208B1/fr not_active Expired - Lifetime
- 1998-01-06 KR KR1019997006241A patent/KR100347472B1/ko not_active Expired - Fee Related
- 1998-01-06 CN CN98801748A patent/CN1093858C/zh not_active Expired - Fee Related
- 1998-01-06 CZ CZ19992436A patent/CZ295580B6/cs not_active IP Right Cessation
- 1998-01-06 SK SK907-99A patent/SK284779B6/sk unknown
- 1998-01-06 DE DE69815313T patent/DE69815313T2/de not_active Expired - Lifetime
- 1998-01-06 AU AU62088/98A patent/AU724990B2/en not_active Ceased
- 1998-01-06 AP APAP/P/1998/001175A patent/AP819A/en active
- 1998-01-06 IL IL13076298A patent/IL130762A/xx not_active IP Right Cessation
- 1998-01-06 EA EA199900531A patent/EA002851B1/ru not_active IP Right Cessation
- 1998-01-07 TN TNTNSN98004A patent/TNSN98004A1/fr unknown
- 1998-01-07 MA MA24920A patent/MA26465A1/fr unknown
- 1998-01-08 AR ARP980100091A patent/AR010396A1/es unknown
- 1998-01-08 HR HR980010A patent/HRP980010B1/xx not_active IP Right Cessation
- 1998-01-09 ZA ZA98166A patent/ZA98166B/xx unknown
- 1998-01-09 MY MYPI98000094A patent/MY119623A/en unknown
- 1998-06-01 UA UA99073901A patent/UA62945C2/uk unknown
- 1998-06-07 DZ DZ980004A patent/DZ2394A1/fr active
1999
- 1999-06-25 IS IS5093A patent/IS2012B/is unknown
- 1999-07-07 BG BG103560A patent/BG63918B1/bg unknown
- 1999-07-08 OA OA9900152A patent/OA11074A/en unknown
- 1999-07-09 NO NO19993396A patent/NO318609B1/no unknown
2000
- 2000-06-02 US US09/586,503 patent/US6365599B1/en not_active Expired - Fee Related
2001
- 2001-11-13 US US10/007,753 patent/US6521629B2/en not_active Expired - Fee Related
2002
- 2002-12-13 US US10/318,902 patent/US6653302B2/en not_active Expired - Fee Related
2003
- 2003-09-17 HK HK03106677.4A patent/HK1054389B/zh not_active IP Right Cessation

Also Published As

Publication number	Publication date
CN1403453A (zh)	2003-03-19
HK1025327A1 (en)	2000-11-10
EA199900531A1 (ru)	2000-02-28
IS5093A (is)	1999-06-25
EA002851B1 (ru)	2002-10-31
PT968208E (pt)	2003-09-30
ATE242238T1 (de)	2003-06-15
CA2277473C (fr)	2003-08-12
TR199901604T2 (xx)	1999-12-21
YU31699A (sh)	2001-07-10
AU6208898A (en)	1998-08-03
US20020040028A1 (en)	2002-04-04
EP0968208A1 (fr)	2000-01-05
OA11074A (en)	2002-03-13
BG63918B1 (bg)	2003-06-30
CZ9902436A3 (cs)	2000-10-11
AR010396A1 (es)	2000-06-07
MY119623A (en)	2005-06-30
SK284779B6 (sk)	2005-11-03
SI0968208T1 (en)	2003-10-31
NO993396D0 (no)	1999-07-09
BR9807068A (pt)	2000-05-02
BG103560A (en)	2000-06-30
IL130762A (en)	2005-12-18
AP9801175A0 (en)	1998-01-31
IS2012B (is)	2005-05-13
JP2000507966A (ja)	2000-06-27
HK1054389B (zh)	2005-10-14
EP0968208B1 (fr)	2003-06-04
WO1998030560A1 (fr)	1998-07-16
KR100347472B1 (ko)	2002-08-07
KR20000070022A (ko)	2000-11-25
PA8444301A1 (es)	2000-05-24
SK90799A3 (en)	2001-03-12
HRP980010A2 (en)	1998-10-31
DZ2394A1 (fr)	2003-06-04
CN1191249C (zh)	2005-03-02
UA62945C2 (en)	2004-01-15
US6521629B2 (en)	2003-02-18
CN1243513A (zh)	2000-02-02
DE69815313T2 (de)	2003-12-11
DE69815313D1 (de)	2003-07-10
PL334678A1 (en)	2000-03-13
AP819A (en)	2000-04-03
TW444013B (en)	2001-07-01
JP3357677B2 (ja)	2002-12-16
MA26465A1 (fr)	2004-12-20
HK1054389A1 (en)	2003-11-28
HN1998000002A (es)	1999-01-08
HRP980010B1 (en)	2002-06-30
TNSN98004A1 (fr)	2005-03-15
HUP0000942A3 (en)	2002-06-28
SA97180705B1 (ar)	2005-12-26
US20030130259A1 (en)	2003-07-10
CA2277473A1 (fr)	1998-07-16
CN1093858C (zh)	2002-11-06
ID21863A (id)	1999-08-05
IL130762A0 (en)	2001-01-28
DK0968208T3 (da)	2003-07-28
CZ295580B6 (cs)	2005-08-17
ZA98166B (en)	1999-07-09
US6169093B1 (en)	2001-01-02
NZ336302A (en)	2000-08-25
ES2198695T3 (es)	2004-02-01
US6653302B2 (en)	2003-11-25
HUP0000942A2 (hu)	2001-04-28
NO993396L (no)	1999-07-09
GB9700504D0 (en)	1997-02-26
US6365599B1 (en)	2002-04-02
PE44499A1 (es)	1999-05-06
AU724990B2 (en)	2000-10-05

Publication	Publication Date	Title
NO318609B1 (no)	2005-04-18	Kinolin- og kinazolinforbindelser nyttige i terapi, spesielt i behandlingen av benign prostatisk hyperplasi
US6103738A (en)	2000-08-15	Quinoline and quinazoline compounds useful in therapy
JP3163281B2 (ja)	2001-05-08	療法において有用なキノリンおよびキナゾリン
AU746586B2 (en)	2002-05-02	Quinazolinone inhibitors of cGMP phosphodiesterase
IE901258L (en)	1990-10-21	Pyrimidine derivatives
US20030045525A1 (en)	2003-03-06	Quinoline and quinazoline compounds useful in therapy
IE61045B1 (en)	1994-09-07	4-aryl-5-carbamoyl-1, 4-dihydropyridines
MXPA98005122A (en)	1999-04-06	Compounds of quinoline and quinazoline useful in tera