NO814239L - Analogifremgangsmaate for fremstilling av terapeutisk aktive pyrimidinon-derivater - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive pyrimidinon-derivaterInfo
- Publication number
- NO814239L NO814239L NO814239A NO814239A NO814239L NO 814239 L NO814239 L NO 814239L NO 814239 A NO814239 A NO 814239A NO 814239 A NO814239 A NO 814239A NO 814239 L NO814239 L NO 814239L
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- methyl
- hydroxy
- group
- dihydro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 5
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 title claims description 3
- 230000001225 therapeutic effect Effects 0.000 title 1
- -1 linear Chemical group 0.000 claims description 106
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 235000005985 organic acids Nutrition 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- FBKXNMHCMNDATN-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-[2-(2-methoxyphenyl)ethylamino]propoxy]phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1)=CC=C1OCC(O)CNCCC1=CC=CC=C1OC FBKXNMHCMNDATN-UHFFFAOYSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical class CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 claims description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- 238000002844 melting Methods 0.000 description 51
- 230000008018 melting Effects 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- 239000000047 product Substances 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 15
- 239000005457 ice water Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- SJIFURHIJRUXOG-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(O)C=C1 SJIFURHIJRUXOG-UHFFFAOYSA-N 0.000 description 6
- XZHGJBCNXCBNTD-UHFFFAOYSA-N 6-methoxy-3-methyl-2-[4-(3-methyloxiran-2-yl)oxyphenyl]quinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1)=CC=C1OC1OC1C XZHGJBCNXCBNTD-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 229910000831 Steel Inorganic materials 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000010959 steel Substances 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- CGEOYYBCLBIBLG-UHFFFAOYSA-N (4-carbonochloridoylphenyl) acetate Chemical compound CC(=O)OC1=CC=C(C(Cl)=O)C=C1 CGEOYYBCLBIBLG-UHFFFAOYSA-N 0.000 description 4
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- NWADIWMATDRHTP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methylpyrido[3,2-d]pyrimidin-4-one Chemical compound N=1C2=CC=CN=C2C(=O)N(C)C=1C1=CC=C(O)C=C1 NWADIWMATDRHTP-UHFFFAOYSA-N 0.000 description 3
- SXOPCLUOUFQBJV-UHFFFAOYSA-N 3-methoxyanthranilic acid Chemical compound COC1=CC=CC(C(O)=O)=C1N SXOPCLUOUFQBJV-UHFFFAOYSA-N 0.000 description 3
- UTJQFGMKKDBGCY-UHFFFAOYSA-N 8-methoxy-3-methyl-2-[4-(3-methyloxiran-2-yl)oxyphenyl]quinazolin-4-one Chemical compound COC1=CC=CC(C(N2C)=O)=C1N=C2C(C=C1)=CC=C1OC1OC1C UTJQFGMKKDBGCY-UHFFFAOYSA-N 0.000 description 3
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 3
- 150000002118 epoxides Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- DEWXUJSUQQMEGM-UHFFFAOYSA-N 1-amino-3-(2-methylphenoxy)propan-2-ol Chemical compound CC1=CC=CC=C1OCC(O)CN DEWXUJSUQQMEGM-UHFFFAOYSA-N 0.000 description 2
- KFQPRNVTVMCYEH-UHFFFAOYSA-N 1-amino-3-(4-methoxyphenoxy)propan-2-ol Chemical compound COC1=CC=C(OCC(O)CN)C=C1 KFQPRNVTVMCYEH-UHFFFAOYSA-N 0.000 description 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 2
- DXYUDCFZHJXQQR-UHFFFAOYSA-N 2-(2-methylphenoxy)ethanamine Chemical compound CC1=CC=CC=C1OCCN DXYUDCFZHJXQQR-UHFFFAOYSA-N 0.000 description 2
- NEWBVXJORIILED-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-6-methoxy-3H-quinazolin-4-one Chemical compound N1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(O)C=C1 NEWBVXJORIILED-UHFFFAOYSA-N 0.000 description 2
- AVWGFHZLPMLKBL-UHFFFAOYSA-N 2-[(4-methoxyphenoxy)methyl]oxirane Chemical compound C1=CC(OC)=CC=C1OCC1OC1 AVWGFHZLPMLKBL-UHFFFAOYSA-N 0.000 description 2
- SNLJHCZFVGHPMU-UHFFFAOYSA-N 2-[4-(3-chloropropoxy)phenyl]-6,7-dimethoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1C1=CC=C(OCCCCl)C=C1 SNLJHCZFVGHPMU-UHFFFAOYSA-N 0.000 description 2
- UYIULMFXOYLZGN-UHFFFAOYSA-N 2-[4-(3-chloropropoxy)phenyl]-8-methoxy-1h-quinazolin-4-one Chemical compound COC1=CC=CC(C(N2)=O)=C1N=C2C1=CC=C(OCCCCl)C=C1 UYIULMFXOYLZGN-UHFFFAOYSA-N 0.000 description 2
- DBBYPRGYMPTFBA-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]-3-methylpyrido[3,2-d]pyrimidin-4-one;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(O)CNC(C)C)=CC=C1C1=NC2=CC=CN=C2C(=O)N1C DBBYPRGYMPTFBA-UHFFFAOYSA-N 0.000 description 2
- RNFBBRXRAZCIBZ-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OCC(O)CNC(C)C)C=C1 RNFBBRXRAZCIBZ-UHFFFAOYSA-N 0.000 description 2
- NJLURZOPCFJTSE-UHFFFAOYSA-N 2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OCC(O)CNC(C)(C)C)C=C1 NJLURZOPCFJTSE-UHFFFAOYSA-N 0.000 description 2
- VNRZBMPXZVTXHP-UHFFFAOYSA-N 2-[4-[3-[[2-hydroxy-3-(3-methylphenoxy)propyl]amino]propoxy]phenyl]-8-methoxy-3-methylquinazolin-4-one Chemical compound COC1=CC=CC(C(N2C)=O)=C1N=C2C(C=C1)=CC=C1OCCCNCC(O)COC1=CC=CC(C)=C1 VNRZBMPXZVTXHP-UHFFFAOYSA-N 0.000 description 2
- ALYFGFPSOPKVNS-UHFFFAOYSA-N 2-[4-[3-[[2-hydroxy-3-(4-methoxyphenoxy)propyl]amino]propoxy]phenyl]-8-methoxy-1h-quinazolin-4-one Chemical compound C1=CC(OC)=CC=C1OCC(O)CNCCCOC1=CC=C(C=2NC3=C(OC)C=CC=C3C(=O)N=2)C=C1 ALYFGFPSOPKVNS-UHFFFAOYSA-N 0.000 description 2
- ZMSOTSKMTKNKDN-UHFFFAOYSA-N 3,6-dimethyl-2-[4-(3-methyloxiran-2-yl)oxyphenyl]quinazolin-4-one Chemical compound CC1OC1OC1=CC=C(C=2N(C(=O)C3=CC(C)=CC=C3N=2)C)C=C1 ZMSOTSKMTKNKDN-UHFFFAOYSA-N 0.000 description 2
- LMZKJYNQAZGRCZ-UHFFFAOYSA-N 3-methyl-2-[4-(3-methyloxiran-2-yl)oxyphenyl]pyrido[3,2-d]pyrimidin-4-one Chemical compound CC1OC1OC1=CC=C(C=2N(C(=O)C3=NC=CC=C3N=2)C)C=C1 LMZKJYNQAZGRCZ-UHFFFAOYSA-N 0.000 description 2
- TYHFXRNZHCEXIB-UHFFFAOYSA-N 3-methyl-2-[4-(3-methyloxiran-2-yl)oxyphenyl]pyrido[4,3-d]pyrimidin-4-one Chemical compound CC1OC1OC1=CC=C(C=2N(C(=O)C3=CN=CC=C3N=2)C)C=C1 TYHFXRNZHCEXIB-UHFFFAOYSA-N 0.000 description 2
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 3H-quinazolinyl-4-one Natural products C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 2
- YBKCTCOYNGKYQF-UHFFFAOYSA-N 6,7-dimethoxy-3-methyl-2-[4-(3-methyloxiran-2-yl)oxyphenyl]quinazolin-4-one Chemical compound CN1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1C(C=C1)=CC=C1OC1OC1C YBKCTCOYNGKYQF-UHFFFAOYSA-N 0.000 description 2
- JRHSJXVSLAJGPW-UHFFFAOYSA-N 6-methoxy-2-[4-(3-methyloxiran-2-yl)oxyphenyl]-1h-quinazolin-4-one Chemical compound N1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1)=CC=C1OC1OC1C JRHSJXVSLAJGPW-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000700199 Cavia porcellus Species 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
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- NSVOQZFPGBZRGH-UHFFFAOYSA-N [4-(6-methoxy-3-methyl-4-oxoquinazolin-2-yl)phenyl] acetate Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OC(C)=O)C=C1 NSVOQZFPGBZRGH-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- 239000003416 antiarrhythmic agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ABXRTJHEVCZIAG-UHFFFAOYSA-N 1-(2-bromoethoxy)-2-methylbenzene Chemical compound CC1=CC=CC=C1OCCBr ABXRTJHEVCZIAG-UHFFFAOYSA-N 0.000 description 1
- UIIJKBSUGZNVQN-UHFFFAOYSA-N 1-(2-bromoethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CCBr UIIJKBSUGZNVQN-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- NIDSRGCVYOEDFW-UHFFFAOYSA-N 1-bromo-4-chlorobutane Chemical compound ClCCCCBr NIDSRGCVYOEDFW-UHFFFAOYSA-N 0.000 description 1
- OOZBNYBOYJYSNZ-UHFFFAOYSA-N 1-chloro-3-(4-methoxyphenoxy)propan-2-ol Chemical compound COC1=CC=C(OCC(O)CCl)C=C1 OOZBNYBOYJYSNZ-UHFFFAOYSA-N 0.000 description 1
- WSWPCNMLEVZGSM-UHFFFAOYSA-N 2-(2-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC=C1CCN WSWPCNMLEVZGSM-UHFFFAOYSA-N 0.000 description 1
- HNJWKRMESUMDQE-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-methylethanamine Chemical compound CNCCC1=CC=C(OC)C(OC)=C1 HNJWKRMESUMDQE-UHFFFAOYSA-N 0.000 description 1
- HYZOQOZLIDGFEJ-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3,6-dimethylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(C)=CC=C2N=C1C1=CC=C(O)C=C1 HYZOQOZLIDGFEJ-UHFFFAOYSA-N 0.000 description 1
- BDSLYJMDXOAUET-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-8-methoxy-3H-quinazolin-4-one Chemical compound COC1=CC=CC(C(N2)=O)=C1N=C2C1=CC=C(O)C=C1 BDSLYJMDXOAUET-UHFFFAOYSA-N 0.000 description 1
- YXRCDWIZAGWUBL-UHFFFAOYSA-N 2-(4-methoxyphenoxy)ethanamine Chemical compound COC1=CC=C(OCCN)C=C1 YXRCDWIZAGWUBL-UHFFFAOYSA-N 0.000 description 1
- NWECCUHLXPLHID-UHFFFAOYSA-N 2-[4-(3-chloropropoxy)phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OCCCCl)C=C1 NWECCUHLXPLHID-UHFFFAOYSA-N 0.000 description 1
- PDANCSHZBVIHGP-UHFFFAOYSA-N 2-[4-(3-chloropropoxy)phenyl]-8-methoxy-3-methylquinazolin-4-one Chemical compound COC1=CC=CC(C(N2C)=O)=C1N=C2C1=CC=C(OCCCCl)C=C1 PDANCSHZBVIHGP-UHFFFAOYSA-N 0.000 description 1
- DCYKKWTUBBUHRT-UHFFFAOYSA-N 2-[4-(4-aminobutoxy)phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OCCCCN)C=C1 DCYKKWTUBBUHRT-UHFFFAOYSA-N 0.000 description 1
- ZSYCKIKTULEMNW-UHFFFAOYSA-N 2-[4-(4-chlorobutoxy)phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OCCCCCl)C=C1 ZSYCKIKTULEMNW-UHFFFAOYSA-N 0.000 description 1
- DUZBAEWJJYPOOR-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]-3,6-dimethylquinazolin-4-one Chemical compound C1=CC(OCC(O)CNC(C)C)=CC=C1C1=NC2=CC=C(C)C=C2C(=O)N1C DUZBAEWJJYPOOR-UHFFFAOYSA-N 0.000 description 1
- XSPJRDSSNLLJRZ-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]-3-methylpyrido[4,3-d]pyrimidin-4-one;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(O)CNC(C)C)=CC=C1C1=NC2=CC=NC=C2C(=O)N1C XSPJRDSSNLLJRZ-UHFFFAOYSA-N 0.000 description 1
- KEYINRMGLHWUCN-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]-6-methoxy-1h-quinazolin-4-one Chemical compound N=1C(=O)C2=CC(OC)=CC=C2NC=1C1=CC=C(OCC(O)CNC(C)C)C=C1 KEYINRMGLHWUCN-UHFFFAOYSA-N 0.000 description 1
- PHRIBAPGGVMXQL-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-[2-(2-methoxyphenyl)ethylamino]propoxy]phenyl]-6-methoxy-3-methylquinazolin-4-one;dihydrochloride Chemical compound Cl.Cl.CN1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1)=CC=C1OCC(O)CNCCC1=CC=CC=C1OC PHRIBAPGGVMXQL-UHFFFAOYSA-N 0.000 description 1
- YZMOFYUUOCIDDG-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-[2-(2-methylphenoxy)ethylamino]propoxy]phenyl]-6,7-dimethoxy-3-methylquinazolin-4-one Chemical group CN1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1C(C=C1)=CC=C1OCC(O)CNCCOC1=CC=CC=C1C YZMOFYUUOCIDDG-UHFFFAOYSA-N 0.000 description 1
- RLRPJUQBOFHHHB-UHFFFAOYSA-N 2-[4-[2-hydroxy-3-[2-(2-methylphenoxy)ethylamino]propoxy]phenyl]-8-methoxy-3-methylquinazolin-4-one Chemical compound COC1=CC=CC(C(N2C)=O)=C1N=C2C(C=C1)=CC=C1OCC(O)CNCCOC1=CC=CC=C1C RLRPJUQBOFHHHB-UHFFFAOYSA-N 0.000 description 1
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- DTHHJNRFHYXJPP-UHFFFAOYSA-N 2-[4-[3-(diethylamino)-2-hydroxypropoxy]phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound C1=CC(OCC(O)CN(CC)CC)=CC=C1C1=NC2=CC=C(OC)C=C2C(=O)N1C DTHHJNRFHYXJPP-UHFFFAOYSA-N 0.000 description 1
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- YDIKNYBOAKPYBD-UHFFFAOYSA-N 2-[4-[3-(diethylamino)propoxy]phenyl]-3-methylquinazolin-4-one;hydroiodide Chemical compound I.C1=CC(OCCCN(CC)CC)=CC=C1C1=NC2=CC=CC=C2C(=O)N1C YDIKNYBOAKPYBD-UHFFFAOYSA-N 0.000 description 1
- QHJGBMKBFISWDX-UHFFFAOYSA-N 2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-6-methoxy-3-propan-2-ylquinazolin-4-one Chemical compound CC(C)N1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OCC(O)CNC(C)(C)C)C=C1 QHJGBMKBFISWDX-UHFFFAOYSA-N 0.000 description 1
- BBXNSDWOXBABKJ-UHFFFAOYSA-N 2-[4-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-hydroxypropoxy]phenyl]-6-methoxy-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1)=CC=C1OCC(O)CN(C)CCC1=CC=C(OC)C(OC)=C1 BBXNSDWOXBABKJ-UHFFFAOYSA-N 0.000 description 1
- VBUXKMVYLBCERW-UHFFFAOYSA-N 2-[4-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]-2-hydroxypropoxy]phenyl]-6-methoxy-3-methylquinazolin-4-one;dihydrochloride Chemical group Cl.Cl.CN1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1)=CC=C1OCC(O)CN(C)CCC1=CC=C(OC)C(OC)=C1 VBUXKMVYLBCERW-UHFFFAOYSA-N 0.000 description 1
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- VTGKBTZAWCWBBG-UHFFFAOYSA-N 6-methoxy-2-[3-methoxy-4-(3-methyloxiran-2-yl)oxyphenyl]-3-methylquinazolin-4-one Chemical compound CN1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1OC)=CC=C1OC1OC1C VTGKBTZAWCWBBG-UHFFFAOYSA-N 0.000 description 1
- PEOVHZUICFZXOP-UHFFFAOYSA-N 6-methoxy-2-[4-(3-methyloxiran-2-yl)oxyphenyl]-3-propan-2-ylquinazolin-4-one Chemical compound CC(C)N1C(=O)C2=CC(OC)=CC=C2N=C1C(C=C1)=CC=C1OC1OC1C PEOVHZUICFZXOP-UHFFFAOYSA-N 0.000 description 1
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 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 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- OESPTPIGTFOPAP-UHFFFAOYSA-N [4-(6-methoxy-4-oxo-3,1-benzoxazin-2-yl)phenyl] acetate Chemical compound O1C(=O)C2=CC(OC)=CC=C2N=C1C1=CC=C(OC(C)=O)C=C1 OESPTPIGTFOPAP-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
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- 150000001350 alkyl halides Chemical class 0.000 description 1
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- 125000003368 amide group Chemical group 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
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- 239000011230 binding agent Substances 0.000 description 1
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- 229910052794 bromium Inorganic materials 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- QYJXDIUNDMRLAO-UHFFFAOYSA-N butyl 4-methylbenzenesulfonate Chemical compound CCCCOS(=O)(=O)C1=CC=C(C)C=C1 QYJXDIUNDMRLAO-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
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- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
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- 208000035475 disorder Diseases 0.000 description 1
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- 238000000921 elemental analysis Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
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- XQUMBKMAOXEAKZ-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)ethyl]propan-1-amine Chemical compound CCCNCCC1=CC=C(OC)C(OC)=C1 XQUMBKMAOXEAKZ-UHFFFAOYSA-N 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 229960001333 nicotinyl methylamide Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
-
- 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
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/20—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 4
- C07D265/22—Oxygen atoms
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19803046871 DE3046871A1 (de) | 1980-12-12 | 1980-12-12 | Neue chinazolinone, ihre herstellung und ihre verwendung als arzneimittel |
| DE19813115447 DE3115447A1 (de) | 1981-04-16 | 1981-04-16 | Neue pyrimidinone, ihre herstellung und ihre verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO814239L true NO814239L (no) | 1982-06-14 |
Family
ID=25789685
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO814239A NO814239L (no) | 1980-12-12 | 1981-12-11 | Analogifremgangsmaate for fremstilling av terapeutisk aktive pyrimidinon-derivater |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US4379788A (es) |
| EP (1) | EP0054132B1 (es) |
| AR (1) | AR227567A1 (es) |
| AU (1) | AU543568B2 (es) |
| CA (1) | CA1217767A (es) |
| CS (1) | CS227024B2 (es) |
| DD (1) | DD208151A5 (es) |
| DE (1) | DE3166627D1 (es) |
| DK (1) | DK525481A (es) |
| ES (2) | ES507761A0 (es) |
| FI (1) | FI813971L (es) |
| GB (1) | GB2090249B (es) |
| GR (1) | GR76952B (es) |
| HU (1) | HU187384B (es) |
| IL (1) | IL64504A (es) |
| MY (1) | MY8700562A (es) |
| NO (1) | NO814239L (es) |
| NZ (1) | NZ199254A (es) |
| PH (1) | PH18930A (es) |
| PL (1) | PL135330B1 (es) |
| PT (1) | PT74116B (es) |
| SU (1) | SU1056900A3 (es) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4460589A (en) * | 1980-10-03 | 1984-07-17 | The Upjohn Company | Process for treating hypertension |
| US4379778A (en) * | 1980-10-10 | 1983-04-12 | Air Products And Chemicals, Inc. | Hydrogen peroxide synthesis |
| DE3428476A1 (de) * | 1984-08-02 | 1986-02-13 | Basf Ag, 6700 Ludwigshafen | 4h-pyrido(2,3-d)(1,3)oxazin-4-on-derivate, verfahren zu ihrer herstellung und ihre verwendung zur bekaempfung unerwuenschten pflanzenwuchses |
| DE3631294A1 (de) * | 1986-09-13 | 1988-03-24 | Thomae Gmbh Dr K | Neue synergistische kombination bestehend aus einem phosphodiesterase-hemmer und einem thromboxan-a(pfeil abwaerts)2(pfeil abwaerts)-antagonisten und deren verwendung bzw. herstellung |
| US5037980A (en) * | 1988-04-18 | 1991-08-06 | American Cyanamid Company | Phenyl imidazo[1,2-a]pyrimidines |
| GB8928346D0 (en) * | 1989-12-15 | 1990-02-21 | Smith Kline French Lab | Chemical compounds |
| GB9126260D0 (en) * | 1991-12-11 | 1992-02-12 | Pfizer Ltd | Therapeutic agents |
| GB9404485D0 (en) * | 1994-03-09 | 1994-04-20 | Cancer Res Campaign Tech | Benzamide analogues |
| CN100430396C (zh) | 1997-11-12 | 2008-11-05 | 拜耳医药保健股份公司 | 用作磷酸二酯酶抑制剂的2-苯基取代的咪唑并三嗪酮 |
| AU2645299A (en) * | 1998-11-18 | 2000-06-05 | Elena Alexandrovna Izaxon | 6-(3-carboxymethylphenyl)-aminouracyl having a biological activity |
| US20040102324A1 (en) | 2002-02-28 | 2004-05-27 | Annis Gary David | Heterocyclic diamide invertebrate pest control agents |
| US6642244B2 (en) | 2001-03-16 | 2003-11-04 | Bristol-Myers Squibb Co. | Pyrazolopyridopyrimidine inhibitors of cGMP phosphodiesterase |
| CN1518447A (zh) * | 2001-04-23 | 2004-08-04 | �������Ǵ�ѧר������� | 作为抗血管生成剂的新的苯邻二甲酰亚胺模拟物的合成和评估 |
| DE50209015D1 (de) * | 2001-05-09 | 2007-02-01 | Bayer Healthcare Ag | NEUE VERWENDUNG VON 2-Ä2-Ethoxy-5-(4-methyl-piperazin-1-sulfonyl)-phenylÜ-5-methyl-7-propyl-3H-imidazoÄ5,1-fÜÄ1,2,4Ütriazin-4-on |
| DE10232113A1 (de) * | 2002-07-16 | 2004-01-29 | Bayer Ag | Vardenafil Hydrochlorid Trihydrat enthaltende Arzneimittel |
| EP1696927A4 (en) * | 2003-12-19 | 2007-10-31 | Merck & Co Inc | MITOTIC INHIBITORS OF KINESIN |
| SE0401342D0 (sv) * | 2004-05-25 | 2004-05-25 | Astrazeneca Ab | Therapeutic compounds |
| SE0401345D0 (sv) * | 2004-05-25 | 2004-05-25 | Astrazeneca Ab | Therapeutic compounds: Pyridine as scaffold |
| JPWO2005115993A1 (ja) * | 2004-05-31 | 2008-03-27 | 萬有製薬株式会社 | キナゾリン誘導体 |
| DE102005001989A1 (de) * | 2005-01-15 | 2006-07-20 | Bayer Healthcare Ag | Intravenöse Formulierungen von PDE-Inhibitoren |
| DE102005009241A1 (de) * | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit kontrollierter Bioverfügbarkeit |
| DE102005009240A1 (de) * | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit verbesserten pharmakokinetischen Eigenschaften |
| EP1931797A2 (en) * | 2005-09-29 | 2008-06-18 | Bayer HealthCare AG | Pde inhibitors and combinations thereof for the treatment of urological disorders |
| CA2663436A1 (en) * | 2006-10-04 | 2008-04-10 | Pfizer Products Inc. | Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists |
| CN101711153A (zh) * | 2007-06-13 | 2010-05-19 | 拜耳先灵制药股份公司 | 用于治疗听觉损伤的pde抑制剂 |
| CN101531638B (zh) * | 2008-03-13 | 2011-12-28 | 中国科学院广州生物医药与健康研究院 | 用作雌激素相关受体调节剂的化合物及其应用 |
| CN102098918A (zh) * | 2008-05-13 | 2011-06-15 | 帕纳德制药公司 | 用于治疗癌症和神经退行性疾病的生物活性化合物 |
| CN101628913B (zh) | 2008-07-18 | 2013-01-23 | 中国科学院广州生物医药与健康研究院 | 用作雌激素相关受体调节剂的化合物及其应用 |
| KR102200628B1 (ko) * | 2012-09-26 | 2021-01-08 | 메르크 파텐트 게엠베하 | Ｐａｒｐ 억제제로서의 퀴나졸리논 유도체 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3265697A (en) * | 1964-09-04 | 1966-08-09 | Shulton Inc | 2-p-dialkylaminoalkoxyphenyl-2, 3-dihydro-4 (1h)-quinazolinones and their derivatives |
| DE1939109A1 (de) * | 1968-08-31 | 1970-03-05 | Troponwerke Dinklage & Co | 2-Methyl-3-[2-(2-diaethylaminoaethoxy)-phenyl]-chinazolinon-(4) und Verfahren zu seiner Herstellung |
| US3862191A (en) * | 1972-09-27 | 1975-01-21 | Pfizer | Pyrido{8 2,3-d{9 pyrimidin-4(3H)-one |
-
1981
- 1981-10-21 EP EP81108623A patent/EP0054132B1/de not_active Expired
- 1981-10-21 DE DE8181108623T patent/DE3166627D1/de not_active Expired
- 1981-11-18 SU SU813354550A patent/SU1056900A3/ru active
- 1981-11-26 DK DK525481A patent/DK525481A/da not_active Application Discontinuation
- 1981-12-04 US US06/327,348 patent/US4379788A/en not_active Expired - Fee Related
- 1981-12-07 ES ES507761A patent/ES507761A0/es active Granted
- 1981-12-07 DD DD81235494A patent/DD208151A5/de unknown
- 1981-12-10 GR GR66768A patent/GR76952B/el unknown
- 1981-12-10 FI FI813971A patent/FI813971L/fi not_active Application Discontinuation
- 1981-12-10 PL PL1981234175A patent/PL135330B1/pl unknown
- 1981-12-10 CS CS819180A patent/CS227024B2/cs unknown
- 1981-12-10 IL IL64504A patent/IL64504A/xx unknown
- 1981-12-11 NO NO814239A patent/NO814239L/no unknown
- 1981-12-11 GB GB8137458A patent/GB2090249B/en not_active Expired
- 1981-12-11 PT PT74116A patent/PT74116B/pt unknown
- 1981-12-11 PH PH26759A patent/PH18930A/en unknown
- 1981-12-11 CA CA000392067A patent/CA1217767A/en not_active Expired
- 1981-12-11 NZ NZ199254A patent/NZ199254A/en unknown
- 1981-12-11 AR AR287776A patent/AR227567A1/es active
- 1981-12-11 AU AU78473/81A patent/AU543568B2/en not_active Ceased
- 1981-12-11 HU HU813747A patent/HU187384B/hu unknown
-
1982
- 1982-04-30 ES ES82511835A patent/ES511835A0/es active Granted
-
1987
- 1987-12-30 MY MY562/87A patent/MY8700562A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DD208151A5 (de) | 1984-03-28 |
| NZ199254A (en) | 1985-02-28 |
| FI813971L (fi) | 1982-06-13 |
| IL64504A (en) | 1985-02-28 |
| PH18930A (en) | 1985-11-11 |
| CA1217767A (en) | 1987-02-10 |
| DE3166627D1 (en) | 1984-11-15 |
| AU543568B2 (en) | 1985-04-26 |
| SU1056900A3 (ru) | 1983-11-23 |
| GR76952B (es) | 1984-09-04 |
| US4379788A (en) | 1983-04-12 |
| ES8207156A1 (es) | 1982-09-01 |
| CS227024B2 (en) | 1984-04-16 |
| GB2090249A (en) | 1982-07-07 |
| AU7847381A (en) | 1982-06-17 |
| ES8304096A1 (es) | 1983-02-16 |
| EP0054132A1 (de) | 1982-06-23 |
| MY8700562A (en) | 1987-12-31 |
| AR227567A1 (es) | 1982-11-15 |
| PL234175A1 (es) | 1982-08-16 |
| IL64504A0 (en) | 1982-03-31 |
| PL135330B1 (en) | 1985-10-31 |
| DK525481A (da) | 1982-06-13 |
| PT74116A (de) | 1982-01-01 |
| PT74116B (de) | 1983-12-19 |
| ES511835A0 (es) | 1983-02-16 |
| GB2090249B (en) | 1984-08-22 |
| ES507761A0 (es) | 1982-09-01 |
| HU187384B (en) | 1985-12-28 |
| EP0054132B1 (de) | 1984-10-10 |
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