DK170669B1 - Analogifremgangsmåde til fremstilling af (piperidinylalkyl)quinazolinderivater - Google Patents
Analogifremgangsmåde til fremstilling af (piperidinylalkyl)quinazolinderivater Download PDFInfo
- Publication number
- DK170669B1 DK170669B1 DK007280A DK7280A DK170669B1 DK 170669 B1 DK170669 B1 DK 170669B1 DK 007280 A DK007280 A DK 007280A DK 7280 A DK7280 A DK 7280A DK 170669 B1 DK170669 B1 DK 170669B1
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- DK
- Denmark
- Prior art keywords
- formula
- parts
- compound
- lower alkyl
- group
- Prior art date
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- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims description 29
- 238000002360 preparation method Methods 0.000 title claims description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 84
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 125000003118 aryl group Chemical group 0.000 claims abstract description 21
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 11
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- 125000001475 halogen functional group Chemical group 0.000 claims abstract description 4
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 4
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims abstract description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 74
- -1 lower all kyloxy Chemical group 0.000 claims description 63
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 42
- 238000003756 stirring Methods 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 238000007363 ring formation reaction Methods 0.000 claims description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 10
- 239000000376 reactant Substances 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 239000002609 medium Substances 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 150000003246 quinazolines Chemical class 0.000 claims description 4
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- ABERUOJGWHYBJL-UHFFFAOYSA-N (4-fluorophenyl)-piperidin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)C1CCNCC1 ABERUOJGWHYBJL-UHFFFAOYSA-N 0.000 claims description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 239000012736 aqueous medium Substances 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- HWFSVCPXNLEACG-UHFFFAOYSA-N 3-(2-chloroethyl)-1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)N(CCCl)C(=O)NC2=C1 HWFSVCPXNLEACG-UHFFFAOYSA-N 0.000 claims description 2
- 238000006214 Clemmensen reduction reaction Methods 0.000 claims description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 2
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 16
- 150000002431 hydrogen Chemical class 0.000 abstract description 8
- 229940076279 serotonin Drugs 0.000 abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- 239000000203 mixture Substances 0.000 description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- 239000000243 solution Substances 0.000 description 54
- 239000011541 reaction mixture Substances 0.000 description 44
- 239000000047 product Substances 0.000 description 40
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 33
- 229960001701 chloroform Drugs 0.000 description 33
- 239000003480 eluent Substances 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000543 intermediate Substances 0.000 description 26
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
- 238000010992 reflux Methods 0.000 description 20
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 18
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical group CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 16
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 15
- 241000700159 Rattus Species 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 239000012258 stirred mixture Substances 0.000 description 11
- 239000000284 extract Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 9
- GPKDBZQZPNOBGM-UHFFFAOYSA-N (4-fluorophenyl)-piperidin-4-ylmethanone;hydron;chloride Chemical compound [Cl-].C1=CC(F)=CC=C1C(=O)C1CC[NH2+]CC1 GPKDBZQZPNOBGM-UHFFFAOYSA-N 0.000 description 8
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
- 230000003902 lesion Effects 0.000 description 7
- 239000012265 solid product Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 238000007126 N-alkylation reaction Methods 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
- 229920002055 compound 48/80 Polymers 0.000 description 6
- 150000002475 indoles Chemical class 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 5
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 5
- 230000010933 acylation Effects 0.000 description 5
- 238000005917 acylation reaction Methods 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 230000008602 contraction Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- YGVBZIRSLJOQNG-UHFFFAOYSA-N 1-(2-chloroethyl)quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(CCCl)C2=C1 YGVBZIRSLJOQNG-UHFFFAOYSA-N 0.000 description 4
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 4
- XFPZFCWGIZKSNI-UHFFFAOYSA-N 2-amino-n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]benzamide Chemical compound NC1=CC=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 XFPZFCWGIZKSNI-UHFFFAOYSA-N 0.000 description 4
- GDFXKHPVAYFLJV-UHFFFAOYSA-N 2-amino-n-[3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl]benzamide Chemical compound NC1=CC=CC=C1C(=O)NCCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 GDFXKHPVAYFLJV-UHFFFAOYSA-N 0.000 description 4
- KLGQWSOYKYFBTR-UHFFFAOYSA-N 2-nitrobenzamide Chemical class NC(=O)C1=CC=CC=C1[N+]([O-])=O KLGQWSOYKYFBTR-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 206010011703 Cyanosis Diseases 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 4
- 239000003420 antiserotonin agent Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 150000002828 nitro derivatives Chemical class 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- KQNZYZBXYOSFGX-UHFFFAOYSA-N 3-(2-chloroethyl)-2-phenylquinazolin-4-one Chemical compound N=1C2=CC=CC=C2C(=O)N(CCCl)C=1C1=CC=CC=C1 KQNZYZBXYOSFGX-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- 239000002262 Schiff base Substances 0.000 description 3
- 150000004753 Schiff bases Chemical class 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
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- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000007248 oxidative elimination reaction Methods 0.000 description 3
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 229930192474 thiophene Natural products 0.000 description 3
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000005907 ketalization reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- WZHJKEUHNJHDLS-QTGUNEKASA-N metergoline Chemical compound C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4N(C)C=C(C=34)C2)C1)C)NC(=O)OCC1=CC=CC=C1 WZHJKEUHNJHDLS-QTGUNEKASA-N 0.000 description 1
- 229960004650 metergoline Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
- AXFCSUUUBXBWSN-UHFFFAOYSA-N methyl 2-(2-hydroxyethylamino)benzoate Chemical compound COC(=O)C1=CC=CC=C1NCCO AXFCSUUUBXBWSN-UHFFFAOYSA-N 0.000 description 1
- 229960001186 methysergide Drugs 0.000 description 1
- 229960003955 mianserin Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000000199 molecular distillation Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- UDEPVPXNQKYIQM-UHFFFAOYSA-N n-(2-bromoethyl)-4-methoxy-2-nitrobenzamide Chemical compound COC1=CC=C(C(=O)NCCBr)C([N+]([O-])=O)=C1 UDEPVPXNQKYIQM-UHFFFAOYSA-N 0.000 description 1
- WORRCRFZVMCBNK-UHFFFAOYSA-N n-(2-chloroethyl)-4-fluoro-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(F)=CC=C1C(=O)NCCCl WORRCRFZVMCBNK-UHFFFAOYSA-N 0.000 description 1
- GCBVUHVWTDLZNH-UHFFFAOYSA-N n-(3-bromopropyl)-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC=CC=C1C(=O)NCCCBr GCBVUHVWTDLZNH-UHFFFAOYSA-N 0.000 description 1
- RIOVDGGXFWHPHE-UHFFFAOYSA-N n-[2-[1-[2-(2,4-dioxo-1h-quinazolin-3-yl)ethyl]piperidine-4-carbonyl]-5-fluorophenyl]formamide Chemical compound O=CNC1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 RIOVDGGXFWHPHE-UHFFFAOYSA-N 0.000 description 1
- JOAIJPABRQMYFS-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-2-nitrobenzamide Chemical class [O-][N+](=O)C1=CC=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 JOAIJPABRQMYFS-UHFFFAOYSA-N 0.000 description 1
- WQRICKXNWYVMSJ-UHFFFAOYSA-N n-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-4-methoxy-2-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC(OC)=CC=C1C(=O)NCCN1CCC(C(=O)C=2C=CC(F)=CC=2)CC1 WQRICKXNWYVMSJ-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 229940098462 oral drops Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- WURFKUQACINBSI-UHFFFAOYSA-M ozonide Chemical compound [O]O[O-] WURFKUQACINBSI-UHFFFAOYSA-M 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- AXKPFOAXAHJUAG-UHFFFAOYSA-N pipamperone Chemical compound C1CC(C(=O)N)(N2CCCCC2)CCN1CCCC(=O)C1=CC=C(F)C=C1 AXKPFOAXAHJUAG-UHFFFAOYSA-N 0.000 description 1
- 229960002776 pipamperone Drugs 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- JUOYGTQAFOURCO-UHFFFAOYSA-N piperidin-4-yl(thiophen-2-yl)methanone;hydrobromide Chemical compound Br.C=1C=CSC=1C(=O)C1CCNCC1 JUOYGTQAFOURCO-UHFFFAOYSA-N 0.000 description 1
- BUDPPMIPWUJUJX-UHFFFAOYSA-N piperidine-4-carbaldehyde;hydrochloride Chemical compound Cl.O=CC1CCNCC1 BUDPPMIPWUJUJX-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- FIADGNVRKBPQEU-UHFFFAOYSA-N pizotifen Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CCC2=C1C=CS2 FIADGNVRKBPQEU-UHFFFAOYSA-N 0.000 description 1
- 229960004572 pizotifen Drugs 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- CSIGAEASXSGNKS-UHFFFAOYSA-N propane-1,1,3-triol Chemical compound OCCC(O)O CSIGAEASXSGNKS-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000006476 reductive cyclization reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 1
- 229950001675 spiperone Drugs 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003564 thiocarbonyl compounds Chemical class 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- 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
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US149379A | 1979-01-08 | 1979-01-08 | |
| US8427279 | 1979-10-12 | ||
| US06/084,272 US4335127A (en) | 1979-01-08 | 1979-10-12 | Piperidinylalkyl quinazoline compounds, composition and method of use |
| US149379 | 1980-05-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK7280A DK7280A (da) | 1980-07-09 |
| DK170669B1 true DK170669B1 (da) | 1995-11-27 |
Family
ID=26669096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK007280A DK170669B1 (da) | 1979-01-08 | 1980-01-07 | Analogifremgangsmåde til fremstilling af (piperidinylalkyl)quinazolinderivater |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4335127A (cs) |
| EP (1) | EP0013612B1 (cs) |
| JP (1) | JPS55105679A (cs) |
| KR (3) | KR850000684B1 (cs) |
| AT (1) | ATE5258T1 (cs) |
| AU (1) | AU536175B2 (cs) |
| CA (1) | CA1132557A (cs) |
| CS (1) | CS223977B2 (cs) |
| CY (1) | CY1252A (cs) |
| DE (1) | DE3065489D1 (cs) |
| DK (1) | DK170669B1 (cs) |
| ES (1) | ES487537A0 (cs) |
| FI (1) | FI66609C (cs) |
| GR (1) | GR67304B (cs) |
| HK (1) | HK76284A (cs) |
| HU (1) | HU184222B (cs) |
| IE (1) | IE49351B1 (cs) |
| IL (1) | IL59084A (cs) |
| LU (1) | LU88219I2 (cs) |
| MA (1) | MA18694A1 (cs) |
| MY (1) | MY8700555A (cs) |
| NL (1) | NL930018I2 (cs) |
| NO (1) | NO155243C (cs) |
| NZ (1) | NZ192551A (cs) |
| PH (1) | PH17114A (cs) |
| PL (1) | PL125789B1 (cs) |
| PT (1) | PT70662A (cs) |
| RO (1) | RO79148A (cs) |
| SG (1) | SG48684G (cs) |
| SU (1) | SU1041034A3 (cs) |
| YU (1) | YU42957B (cs) |
| ZA (1) | ZA8082B (cs) |
Families Citing this family (111)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA806501B (en) * | 1979-10-27 | 1981-10-28 | Richardson Merrell Inc | 4-(4-alkyl-aroyl-1-piperidino)butyrophenone antipsychotic agents |
| CA1183847A (en) * | 1981-10-01 | 1985-03-12 | Georges Van Daele | N-(3-hydroxy-4-piperidinyl)benzamide derivatives |
| US4355037A (en) * | 1981-11-12 | 1982-10-19 | Hoechst-Roussel Pharmaceuticals | 3-(4-Piperidyl)-1,2-benzisoxales |
| DK159420C (da) * | 1983-03-09 | 1991-03-11 | Ciba Geigy Ag | N-(piperidinyl-alkyl)-carboxamider og salte deraf, farmaceutiske praeparater indeholdende disse forbindelser samt anvendelsen af forbindelserne til fremstilling af antipsykotiske farmaceutiske praeparater |
| ZA841728B (en) * | 1983-03-09 | 1984-11-28 | Ciba Geigy Ag | Novel carboxamides |
| JPS608274A (ja) * | 1983-06-27 | 1985-01-17 | Fujisawa Pharmaceut Co Ltd | 新規キナゾリノン誘導体およびその製造法・並びに抗アレルギ−剤 |
| PH23995A (en) * | 1984-01-09 | 1990-02-09 | Janssen Pharmaceutica Nv | 4((bicycle heterocyclyl)-methyl and hetero)piperidines |
| CS247557B1 (en) * | 1984-04-06 | 1987-01-15 | Ludmila Fisnerova | Esters of 3-(2-hydroxyethyl)-4(3h)-quinazolinone |
| EP0177078A1 (en) * | 1984-09-12 | 1986-04-09 | Duphar International Research B.V | Spasmolytically active tertiary amine derivatives and method of preparing the same |
| US4634769A (en) * | 1984-09-25 | 1987-01-06 | Ortho Pharmaceutical Corporation | Process for the preparation of 8-halo-5,6-dialkoxyquinazoline-2,4-diones and their salts |
| US4665075A (en) * | 1984-12-05 | 1987-05-12 | Janssen Pharmaceutica N.V. | Derivatives of hydroxy- or amino-substituted (piperidinylalkyl)quinazolines |
| CA1246074A (en) * | 1984-12-05 | 1988-12-06 | Albertus H.M.T. Van Heertum | Derivatives of hydroxy- or amino-substituted (piperidinylalkyl)quinazolines |
| US4804663A (en) * | 1985-03-27 | 1989-02-14 | Janssen Pharmaceutica N.V. | 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles |
| JPH0615529B2 (ja) * | 1985-04-01 | 1994-03-02 | エーザイ株式会社 | 新規ピペリジン誘導体 |
| FR2581993B1 (fr) * | 1985-05-14 | 1988-03-18 | Synthelabo | Derives de (benzoyl-4 piperidino)-2 phenyl-1 alcanols, leur preparation et leur application en therapeutique |
| US4710502A (en) * | 1985-11-04 | 1987-12-01 | American Cyanamid Company | 3-heteroarylalkyl-4-quinazolinones |
| US4753944A (en) * | 1985-11-04 | 1988-06-28 | American Cyanamid Company | Pharmaceutical methods of using 3-heteroarylalkyl-4-quinazolinones |
| DK623586A (da) * | 1985-12-27 | 1987-06-28 | Eisai Co Ltd | Piperidinderivater eller salte deraf og farmaceutiske kompositioner indeholdende forbindelserne |
| DE3751974T2 (de) * | 1986-09-22 | 1997-04-10 | Janssen Pharmaceutica Nv | Serotonin-Antagonisten zur Behandlung von Wunden |
| US4874766A (en) * | 1986-09-22 | 1989-10-17 | Janssen Pharmaceutica N.V. | Method of promoting wound-healing |
| AU593194B2 (en) * | 1986-09-26 | 1990-02-01 | Sumitomo Pharmaceuticals Company, Limited | Imide derivatives ,and their production and use |
| DE3738844A1 (de) * | 1987-11-16 | 1989-05-24 | Merck Patent Gmbh | Analgetikum |
| EP0335442B1 (en) * | 1988-03-28 | 1996-05-15 | Janssen Pharmaceutica N.V. | Agents for preserving or restoring the soundness of the skin |
| IL90879A0 (en) * | 1988-09-02 | 1990-02-09 | Janssen Pharmaceutica Nv | 3-piperidinyl-indazole derivatives,their preparation and antihypertensive compositions containing them |
| CA1340821C (en) * | 1988-10-06 | 1999-11-16 | Nobuyuki Fukazawa | Heterocyclic compounds and anticancer-drug reinforcing agents containing them as effective components |
| FR2644786B1 (fr) * | 1989-03-21 | 1993-12-31 | Adir Cie | Nouveaux derives fluoro-4 benzoiques, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent |
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| US3322766A (en) * | 1964-11-13 | 1967-05-30 | Shulton Inc | 3-beta-(4-pyridyl) ethyl-2, 3-dihydro-4(1h)-quinazolinones |
| US3635976A (en) * | 1967-12-20 | 1972-01-18 | Pennwalt Corp | 1 - heterocyclic alkyl-1 2 3 4-tetrahydroquinazolinones and analgesic intermediates thereof |
| US4096144A (en) * | 1970-12-08 | 1978-06-20 | Sumitomo Chemical Company, Limited | Process for preparing quinazolinone derivatives and their 2-(N-mono-substituted amino)-phenyl ketone intermediate derivatives |
| US4099002A (en) * | 1970-12-23 | 1978-07-04 | Sumitomo Chemical Company, Limited | Quinazolinone derivatives and a process for production thereof |
| US4146717A (en) * | 1972-04-07 | 1979-03-27 | Sumitomo Chemical Company, Limited | Nitroquinazolinone compounds having antiviral properties |
| US4035369A (en) * | 1975-10-08 | 1977-07-12 | Janssen Pharmaceutica N.V. | 1-Benzazolylalkyl-4-substituted-piperidines |
-
1979
- 1979-10-12 US US06/084,272 patent/US4335127A/en not_active Expired - Lifetime
- 1979-12-21 GR GR60828A patent/GR67304B/el unknown
-
1980
- 1980-01-04 MA MA18891A patent/MA18694A1/fr unknown
- 1980-01-07 LU LU88219C patent/LU88219I2/xx unknown
- 1980-01-07 DK DK007280A patent/DK170669B1/da not_active IP Right Cessation
- 1980-01-07 FI FI800047A patent/FI66609C/fi not_active IP Right Cessation
- 1980-01-07 EP EP80300059A patent/EP0013612B1/en not_active Expired
- 1980-01-07 IL IL59084A patent/IL59084A/xx unknown
- 1980-01-07 JP JP18680A patent/JPS55105679A/ja active Granted
- 1980-01-07 ZA ZA00800082A patent/ZA8082B/xx unknown
- 1980-01-07 SU SU802863403A patent/SU1041034A3/ru active
- 1980-01-07 DE DE8080300059T patent/DE3065489D1/de not_active Expired
- 1980-01-07 AU AU54381/80A patent/AU536175B2/en not_active Expired
- 1980-01-07 CS CS80157A patent/CS223977B2/cs unknown
- 1980-01-07 CY CY1252A patent/CY1252A/xx unknown
- 1980-01-07 IE IE21/80A patent/IE49351B1/en not_active IP Right Cessation
- 1980-01-07 HU HU8025A patent/HU184222B/hu unknown
- 1980-01-07 AT AT80300059T patent/ATE5258T1/de not_active IP Right Cessation
- 1980-01-07 NO NO800034A patent/NO155243C/no unknown
- 1980-01-07 PL PL1980221249A patent/PL125789B1/pl unknown
- 1980-01-07 CA CA343,181A patent/CA1132557A/en not_active Expired
- 1980-01-07 NZ NZ192551A patent/NZ192551A/en unknown
- 1980-01-07 PT PT70662A patent/PT70662A/pt unknown
- 1980-01-08 ES ES487537A patent/ES487537A0/es active Granted
- 1980-01-08 YU YU46/80A patent/YU42957B/xx unknown
- 1980-01-08 PH PH23489A patent/PH17114A/en unknown
- 1980-01-21 KR KR1019800000201A patent/KR850000684B1/ko not_active Expired
- 1980-02-20 RO RO80100248A patent/RO79148A/ro unknown
-
1984
- 1984-07-06 SG SG486/84A patent/SG48684G/en unknown
- 1984-08-02 KR KR1019840004608A patent/KR850000677B1/ko not_active Expired
- 1984-10-11 HK HK762/84A patent/HK76284A/en not_active IP Right Cessation
- 1984-12-20 KR KR1019840008162A patent/KR850000683B1/ko not_active Expired
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1987
- 1987-12-30 MY MY555/87A patent/MY8700555A/xx unknown
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1993
- 1993-03-02 NL NL930018C patent/NL930018I2/nl unknown
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| B1 | Patent granted (law 1993) | ||
| PUP | Patent expired |