FI66609C - Foerfarande foer framstaellning av nya terapeutiskt anvaendbara (piperidinylalkyl)kinazolinderivat - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt anvaendbara (piperidinylalkyl)kinazolinderivat Download PDFInfo
- Publication number
- FI66609C FI66609C FI800047A FI800047A FI66609C FI 66609 C FI66609 C FI 66609C FI 800047 A FI800047 A FI 800047A FI 800047 A FI800047 A FI 800047A FI 66609 C FI66609 C FI 66609C
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- Finland
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- formula
- compound
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- lower alkyl
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- 150000001875 compounds Chemical class 0.000 claims abstract description 94
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 125000001424 substituent group Chemical group 0.000 claims abstract description 13
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 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 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 125000001544 thienyl 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
- -1 sulfonyloxy group Chemical group 0.000 claims description 88
- 238000003756 stirring Methods 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 24
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 16
- 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
- 239000000376 reactant Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 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 claims description 10
- 239000002585 base Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004442 acylamino group Chemical group 0.000 claims description 5
- 239000002609 medium Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 239000004202 carbamide Substances 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000012736 aqueous medium Substances 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims 1
- 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 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 14
- 150000002431 hydrogen Chemical class 0.000 abstract description 7
- 229940076279 serotonin Drugs 0.000 abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- 239000000203 mixture Substances 0.000 description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- 239000011541 reaction mixture Substances 0.000 description 44
- 239000000047 product Substances 0.000 description 43
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 42
- 239000003480 eluent Substances 0.000 description 35
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 229960001701 chloroform Drugs 0.000 description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 29
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
- 239000000243 solution Substances 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 21
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- 229910000029 sodium carbonate Inorganic materials 0.000 description 14
- 150000002148 esters Chemical group 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000007126 N-alkylation reaction Methods 0.000 description 12
- 241000700159 Rattus Species 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- NAYYNDKKHOIIOD-UHFFFAOYSA-N phthalamide Chemical compound NC(=O)C1=CC=CC=C1C(N)=O NAYYNDKKHOIIOD-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- 239000012258 stirred mixture Substances 0.000 description 10
- 150000002828 nitro derivatives Chemical class 0.000 description 9
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 208000014674 injury Diseases 0.000 description 7
- 239000012265 solid product Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 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
- KLGQWSOYKYFBTR-UHFFFAOYSA-N 2-nitrobenzamide Chemical class NC(=O)C1=CC=CC=C1[N+]([O-])=O KLGQWSOYKYFBTR-UHFFFAOYSA-N 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 4
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000005069 ears Anatomy 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 229930192474 thiophene Natural products 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- BHWNQRHBJTYLBS-UHFFFAOYSA-N (3-methylphenyl)-(1-methylpiperidin-4-yl)methanone Chemical compound C1CN(C)CCC1C(=O)C1=CC=CC(C)=C1 BHWNQRHBJTYLBS-UHFFFAOYSA-N 0.000 description 2
- ABERUOJGWHYBJL-UHFFFAOYSA-N (4-fluorophenyl)-piperidin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)C1CCNCC1 ABERUOJGWHYBJL-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 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 2
- XPJSGHCKVFWOLW-UHFFFAOYSA-N 1-(2-hydroxyethyl)quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(CCO)C2=C1 XPJSGHCKVFWOLW-UHFFFAOYSA-N 0.000 description 2
- XXGTWVXNXIPFBX-UHFFFAOYSA-N 1-(3-chloropropyl)-2,2-dimethyl-3h-quinazolin-4-one Chemical compound C1=CC=C2N(CCCCl)C(C)(C)NC(=O)C2=C1 XXGTWVXNXIPFBX-UHFFFAOYSA-N 0.000 description 2
- SOCVLUBVKLOUJM-UHFFFAOYSA-N 1-(3-chloropropyl)quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(CCCCl)C2=C1 SOCVLUBVKLOUJM-UHFFFAOYSA-N 0.000 description 2
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 2
- JHASHLIKVNVRHG-UHFFFAOYSA-N 3-(2-hydroxyethyl)-2-phenylquinazolin-4-one Chemical compound N=1C2=CC=CC=C2C(=O)N(CCO)C=1C1=CC=CC=C1 JHASHLIKVNVRHG-UHFFFAOYSA-N 0.000 description 2
- YUIZZKJVRNHLGO-UHFFFAOYSA-N 3-(2-hydroxyethyl)-4-methyl-1,4-dihydroquinazolin-2-one Chemical compound C1=CC=C2C(C)N(CCO)C(=O)NC2=C1 YUIZZKJVRNHLGO-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- MYGXGCCFTPKWIH-UHFFFAOYSA-N 4-chloro-1-methylpiperidine Chemical compound CN1CCC(Cl)CC1 MYGXGCCFTPKWIH-UHFFFAOYSA-N 0.000 description 2
- UDYCZQSEAXVJEL-UHFFFAOYSA-N 4-fluoro-n-(2-hydroxyethyl)-2-nitrobenzamide Chemical compound OCCNC(=O)C1=CC=C(F)C=C1[N+]([O-])=O UDYCZQSEAXVJEL-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- HDMBIFHPGBKECJ-UHFFFAOYSA-N 6-chloro-3-(2-chloroethyl)-4-phenyl-1,4-dihydroquinazolin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N(CCCl)C1C1=CC=CC=C1 HDMBIFHPGBKECJ-UHFFFAOYSA-N 0.000 description 2
- VNEIHOLJEZRVCL-UHFFFAOYSA-N 6-fluoro-3-piperidin-4-yl-1h-indole Chemical compound C=1NC2=CC(F)=CC=C2C=1C1CCNCC1 VNEIHOLJEZRVCL-UHFFFAOYSA-N 0.000 description 2
- OMRCYTJAXDCWQE-UHFFFAOYSA-N 7-chloro-3-(2-hydroxyethyl)-1h-quinazoline-2,4-dione Chemical compound ClC1=CC=C2C(=O)N(CCO)C(=O)NC2=C1 OMRCYTJAXDCWQE-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
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- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- CCAZWUJBLXKBAY-ULZPOIKGSA-N Tutin Chemical compound C([C@]12[C@@H]3O[C@@H]3[C@@]3(O)[C@H]4C(=O)O[C@@H]([C@H]([C@]32C)O)[C@H]4C(=C)C)O1 CCAZWUJBLXKBAY-ULZPOIKGSA-N 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- MRLURGPACCEDSO-UHFFFAOYSA-N [4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]-phenylmethanone Chemical compound C12=CC(F)=CC=C2NC=C1C(CC1)CCN1C(=O)C1=CC=CC=C1 MRLURGPACCEDSO-UHFFFAOYSA-N 0.000 description 1
- GKSLJBLJZUHOHX-UHFFFAOYSA-N [4-(6-fluoro-1h-indol-3-yl)-4h-pyridin-1-yl]-phenylmethanone Chemical compound C=1NC2=CC(F)=CC=C2C=1C(C=C1)C=CN1C(=O)C1=CC=CC=C1 GKSLJBLJZUHOHX-UHFFFAOYSA-N 0.000 description 1
- YIBISYBTMBAQIX-UHFFFAOYSA-N [4-(6-fluoro-1h-indol-3-yl)piperidin-1-yl]-phenylmethanone Chemical compound C=1NC2=CC(F)=CC=C2C=1C(CC1)CCN1C(=O)C1=CC=CC=C1 YIBISYBTMBAQIX-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
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- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000008359 benzonitriles Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
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- 238000006482 condensation reaction Methods 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
- 229960001140 cyproheptadine Drugs 0.000 description 1
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- 238000010511 deprotection reaction Methods 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- PMIVRZGTYMKJMR-UHFFFAOYSA-N ethyl 3,5-dichloro-2-(ethoxycarbonylamino)benzoate Chemical compound CCOC(=O)NC1=C(Cl)C=C(Cl)C=C1C(=O)OCC PMIVRZGTYMKJMR-UHFFFAOYSA-N 0.000 description 1
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 1
- FZEOURQRKPFNQR-UHFFFAOYSA-N ethyl 4-(2-methylbenzoyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C(=O)C1=CC=CC=C1C FZEOURQRKPFNQR-UHFFFAOYSA-N 0.000 description 1
- WMYNMWHPJYJFSI-UHFFFAOYSA-N ethyl 4-(4-bromobenzoyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C(=O)C1=CC=C(Br)C=C1 WMYNMWHPJYJFSI-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000006332 fluoro benzoyl group Chemical group 0.000 description 1
- GTASXTHTWMWIKA-UHFFFAOYSA-N formaldehyde;hydrobromide Chemical compound Br.O=C GTASXTHTWMWIKA-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 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
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000001990 intravenous administration Methods 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
- 150000002576 ketones Chemical class 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 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
- 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
- 229960001186 methysergide Drugs 0.000 description 1
- 229960003955 mianserin Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000000199 molecular distillation Methods 0.000 description 1
- 239000012452 mother liquor Substances 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
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002560 nitrile group Chemical group 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
- 238000010606 normalization Methods 0.000 description 1
- GTDQGKWDWVUKTI-UHFFFAOYSA-N o-aminoacetophenone Chemical compound CC(=O)C1=CC=CC=C1N GTDQGKWDWVUKTI-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 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
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 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
- 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
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 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
- 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
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000004206 stomach function Effects 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003564 thiocarbonyl compounds Chemical class 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 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
- 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
- 208000027185 varicose disease Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 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)
Claims (2)
1. Förfarande för framställning av nya, terapeutiskt användbara (piperidinylalkyl)kinazolinderivat med den allmänna formeIn I R Q-Alk- A, „ och de farmaceutiskt godtagbara syraadditionssalterna därav, varvid Alk är en alkylenkedja med 1-4 kolatomer; Q är en kinazolinylgrupp, vars 1-, 2-, 3- eller 4-ställning är förenad med alkylensidokedjän, och kinazolinylgruppen i ena eller vardera av 2- och 4-ställningarna bär en karbonyl- eller tiokarbonylgrupp och bensenringen i kinazolinylgruppen är even-tuellt substituerad med 1-3 substituenter, vilka oberoende av varandra betecknar halogen, lägre alkyl, lägre alkyloxi, nitro eller trifluormetyl, och pyrimidinoringen av kinazolinylgruppen kan vara partiellt eller helt mättad och eventuellt substituerad med 1-3 substituenter, vilka oberoende av varandra betecknar lägre alkyl eller Ar som betecknar fenyl, substituerad fenyl eller pyridinyl, varvid den substituerade fenylgruppen har 1-3 substituenter som oberoende av varandra betecknar halogen, lägre alkyl eller lägre alkyloxi; R är väte, hydroxi eller lägre alkyl; och Z är en grupp med formeln -X-Ar eller \—/ 1, väri X är en grupp med formeln R 57 6 6 6 0 9 2 /'‘K >C = 0, ^?CH0H, >CH-0-C-Ra, eller >C (CH2>2 väri R är lägre alkyl; och 8 ® R är väte, halogen, lägre alkyl eller lägre alkyloxi; och Ar är fenyl, substituerad fenyl, tienyl eller pyridinyl, varvid den substituerade fenylgruppen har 1-3 substituenter som oberoen-de av varandra betecknar halogen, lägre alkyl, lägre alkyloxi, trifluormetyl eller amino, kännnetecknat därav, att a) man omsätter en förening med formeln (II) Q-Alk-W (II) väri W är en reaktiv esterrest, säsom halogen, eller en sulfon-yloxigrupp, säsom metylsulfonyloxigrupp, eller 4-metylfenyl-sulfonyloxigrupp, med en förening med formeln (III) Z (HI) vid en förhöjd temperatur i ett lämpligt reaktionsinert organiskt lösningsmedel och i närvaro av en lämplig bas, eller b) för framställning av en förening med formeln (I-a) K* 2 3 4 5 väri en av gruppen R , R , R och R är D och D är en grupp med formeln 58 6 6 6 0 9 R -Alk-{^—x'Ar
2. U 5 och var och en av de äterstdende grupperna R , R , R och R oberoende av de andra betecknar väte, lägre alkyl, aryl eller aryl(lägre alkyl); R^ är halogen, lägre alkyl, lägre alkyloxi, trifluormetyl, nitro eller cyan; varje Y är 0 eller S; och n är ett heltal 0-3, man cykliserar en förening med formeln (IV-a) Y . C-NH-R2 (Rl)n—(IV-a) I 3 ΪΤ med en förening med formeln (V) u R Y = (V) \r5 genom omrörande av reaktanterna tillsammans i ett lämpligt lös-ningsmedel vid en förhöjd temperatur, och ifall önskvärt, kan i cykliseringsreaktionen föreningen med formeln (V) ersättas med ett lämpligt funktionellt ekvivalent derivat därav, säsom ett di(lägre alkyDacetal eller ett cykliskt acetal, eller c) för framställning av en förening med formeln (I-b) <v-o6c R4 man cykliserar en förening med formeln (VI) 59 6 6 6 0 9 Y Il 2 C-NH-R CRl)_fY <VI) H Y
2 H väri den ena av gruppernaR och R är D och den andra är väte , lägre alkyl, aryl eller aryl(lägre alkyl), genom omröring och upp-värmning av 2-(acylamino)bensamid eller -bensentioamid (VI) i ett lämpligt reaktionsinert lösningsmedel i närvaro av en lämp-lig bas, eller d) för framställning av en förening med formeln (I-c) (Ri)n"CxVR2 (i'c) i3 Rd 2 3 väri den ena av gruppema R och R är D, och D betecknar detsamma som ovan, och den andra är väte, lägre alkyl, aryl eller aryl-(lägre alkyl), R^ och n betecknar detsamma som ovan och varje Y betecknar självständigt 0 eller S, man cykliserar en förening med formeln (IV-a) säsom ovan definierats, med urea eller tio-urea genom omrörande av reaktanterna tillsammans vid en förhöjd temperatur i närvaro av ett lämpligt lösningsmedel, eller e) för framställning av en förening med formeln (I-c-1) ‘"‘’"“OÖr TM H 1 man cyklicerar en förening med formeln (IV-c) so 66609 γ <κ\-£ίζ av-c) ^N = C-Y med en förening med formeln (VIII-a) D-NH2 (VII)-a)
0 T varvid R betecknar en lämplig avglende grupp och R , n och Y betecknar detsanuna som ovan, genom omrörande av reaktanterna tillsammans vid en förhöjd temperatur i närvaro av ett lämpligt lösningsmedel, eller f) för framställning av en förening med formeln (I-e) R8 R / Q-Alk-li^^/7!- R9 '-f (I-e) nh2 8 9 väri R och R självständigt är väte, halogen, lägre alkyl, lägre alkyloxi, trifluormetyl eller amino, man hydrolyserar en förening med formeln (XIII) R r8 Q.Alk./K_S_^_R9 <XIII) NfiCHO i ett surt medium, eller g) för framställning av en förening med formeln (I-f) / OH Q-Alk-N^y—CH-Ar (I-f)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US149379A | 1979-01-08 | 1979-01-08 | |
| US149379 | 1979-01-08 | ||
| US06/084,272 US4335127A (en) | 1979-01-08 | 1979-10-12 | Piperidinylalkyl quinazoline compounds, composition and method of use |
| US8427279 | 1979-10-12 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI800047A FI800047A (fi) | 1980-07-09 |
| FI66609B FI66609B (fi) | 1984-07-31 |
| FI66609C true FI66609C (fi) | 1984-11-12 |
Family
ID=26669096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI800047A FI66609C (fi) | 1979-01-08 | 1980-01-07 | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara (piperidinylalkyl)kinazolinderivat |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4335127A (sv) |
| EP (1) | EP0013612B1 (sv) |
| JP (1) | JPS55105679A (sv) |
| KR (3) | KR850000684B1 (sv) |
| AT (1) | ATE5258T1 (sv) |
| AU (1) | AU536175B2 (sv) |
| CA (1) | CA1132557A (sv) |
| CS (1) | CS223977B2 (sv) |
| CY (1) | CY1252A (sv) |
| DE (1) | DE3065489D1 (sv) |
| DK (1) | DK170669B1 (sv) |
| ES (1) | ES487537A0 (sv) |
| FI (1) | FI66609C (sv) |
| GR (1) | GR67304B (sv) |
| HK (1) | HK76284A (sv) |
| HU (1) | HU184222B (sv) |
| IE (1) | IE49351B1 (sv) |
| IL (1) | IL59084A (sv) |
| LU (1) | LU88219I2 (sv) |
| MA (1) | MA18694A1 (sv) |
| MY (1) | MY8700555A (sv) |
| NL (1) | NL930018I2 (sv) |
| NO (1) | NO155243C (sv) |
| NZ (1) | NZ192551A (sv) |
| PH (1) | PH17114A (sv) |
| PL (1) | PL125789B1 (sv) |
| PT (1) | PT70662A (sv) |
| RO (1) | RO79148A (sv) |
| SG (1) | SG48684G (sv) |
| SU (1) | SU1041034A3 (sv) |
| YU (1) | YU42957B (sv) |
| ZA (1) | ZA8082B (sv) |
Families Citing this family (112)
| 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 |
| ZA841728B (en) * | 1983-03-09 | 1984-11-28 | Ciba Geigy Ag | Novel carboxamides |
| 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 |
| 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 |
| US4874766A (en) * | 1986-09-22 | 1989-10-17 | Janssen Pharmaceutica N.V. | Method of promoting wound-healing |
| EP0268309B1 (en) * | 1986-09-22 | 1996-12-11 | Janssen Pharmaceutica N.V. | Serotonin antagonists for treating wounds |
| JP2660407B2 (ja) * | 1986-09-26 | 1997-10-08 | 住友製薬株式会社 | 新規なイミド誘導体 |
| JPH0434361Y2 (sv) * | 1986-12-25 | 1992-08-17 | ||
| DE3738844A1 (de) * | 1987-11-16 | 1989-05-24 | Merck Patent Gmbh | Analgetikum |
| NZ228447A (en) * | 1988-03-28 | 1990-08-28 | Janssen Pharmaceutica Nv | Cosmetic or pharmaceutical composition possessing serotonin antogonistic activity |
| 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 |
| JP2744634B2 (ja) * | 1989-04-14 | 1998-04-28 | 三菱重工業株式会社 | ゴミ焼却装置 |
| US5561128A (en) * | 1989-05-19 | 1996-10-01 | Hoechst-Roussel Pharmaceuticals, Inc. | N-[(4-(heteroaryl)-1-piperidinyl)alkyl]-10,11-dihydro-5H-dibenz[B,F]azepines and related compounds and their therapeutic utility |
| US5364866A (en) * | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
| US5776963A (en) * | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
| IE913473A1 (en) * | 1990-10-15 | 1992-04-22 | Fujisawa Pharmaceutical Co | Quinazoline derivatives and their preparation |
| US5158953A (en) * | 1991-08-13 | 1992-10-27 | National Science Council | 2-substituted methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (thiones), the preparation and use thereof |
| DE4138756A1 (de) * | 1991-11-26 | 1993-05-27 | Troponwerke Gmbh & Co Kg | Kombination mit neuroprotektiver wirkung |
| US5266571A (en) * | 1992-01-09 | 1993-11-30 | Amer Moh Samir | Treatment of hemorrhoids with 5-HT2 antagonists |
| GB9202915D0 (en) * | 1992-02-12 | 1992-03-25 | Wellcome Found | Chemical compounds |
| AU669156B2 (en) * | 1992-02-13 | 1996-05-30 | Merrell Dow Pharmaceuticals Inc. | Piperidinyl thiacyclic derivatives |
| FR2696744B1 (fr) * | 1992-10-12 | 1994-12-30 | Logeais Labor Jacques | Dérivés de 2-pyrrolidone, leur procédé de préparation et leurs applications en thérapeutique. |
| DE69415391T2 (de) * | 1993-05-26 | 1999-08-26 | Sumitomo Pharmaceuticals Co. | Chinazolinonderivate |
| ES2236700T3 (es) * | 1993-11-19 | 2005-07-16 | Janssen Pharmaceutica N.V. | 1,2-benzazoles microencapsulados. |
| EP0661266A1 (en) * | 1993-12-27 | 1995-07-05 | Toa Eiyo Ltd. | Substituted cyclic amine compounds as 5HT2 antagonists |
| US6184377B1 (en) | 1997-12-15 | 2001-02-06 | Sepracor Inc. | Compositions containing N-amino- and N-hydroxy-quinazolinones and methods for preparing libraries thereof |
| DE69926776T2 (de) * | 1998-10-16 | 2006-06-08 | Sumitomo Pharmaceuticals Co., Ltd. | Quinalozinon-derivate |
| GB9903784D0 (en) * | 1999-02-18 | 1999-04-14 | Lilly Co Eli | Pharmaceutical compounds |
| PL350904A1 (en) | 1999-03-26 | 2003-02-10 | Astrazeneca Ab | Novel compounds |
| US6476041B1 (en) * | 1999-10-29 | 2002-11-05 | Merck & Co., Inc. | 1,4 substituted piperidinyl NMDA/NR2B antagonists |
| US6844338B2 (en) | 2000-05-18 | 2005-01-18 | Eli Lilly And Company | Piperidyindoles as serotonin receptor ligands |
| GB2362381A (en) * | 2000-05-18 | 2001-11-21 | Lilly Co Eli | Pharmaceutically active indolyl-piperidines |
| GB0013060D0 (en) * | 2000-05-31 | 2000-07-19 | Astrazeneca Ab | Chemical compounds |
| GB0021670D0 (en) * | 2000-09-04 | 2000-10-18 | Astrazeneca Ab | Chemical compounds |
| DE10101324C1 (de) * | 2001-01-13 | 2001-12-13 | Ibfb Gmbh Privates Inst Fuer B | 1-Dimercaptoalkylchinazolin-2,4-(1H,3H)-dione als Matrix-Metalloproteinase(MMP)-Inhibitoren |
| GB0117899D0 (en) * | 2001-07-23 | 2001-09-12 | Astrazeneca Ab | Chemical compounds |
| SE0102809D0 (sv) * | 2001-08-22 | 2001-08-22 | Astrazeneca Ab | Novel compounds |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| TW200813014A (en) * | 2002-03-28 | 2008-03-16 | Astrazeneca Ab | Quinazoline derivatives |
| US6924285B2 (en) * | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| EP1560814A1 (en) * | 2002-11-13 | 2005-08-10 | Synthon B.V. | Process for making risperidone and intermediates therefor |
| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| WO2004094415A1 (en) * | 2003-04-22 | 2004-11-04 | Synthon B.V. | Risperidone monohydrochloride |
| GB0309850D0 (en) * | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| US20080234263A1 (en) * | 2003-09-16 | 2008-09-25 | Laurent Francois Andre Hennequin | Quinazoline Derivatives |
| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| DK1667991T3 (da) * | 2003-09-16 | 2008-08-18 | Astrazeneca Ab | Quinazolinderivater som tyrosinkinaseinhibitorer |
| CN1882573A (zh) * | 2003-09-16 | 2006-12-20 | 阿斯利康(瑞典)有限公司 | 作为酪氨酸激酶抑制剂的喹唑啉衍生物 |
| DK1667992T3 (da) * | 2003-09-19 | 2007-04-30 | Astrazeneca Ab | Quinazolinderivater |
| WO2005028470A1 (en) * | 2003-09-19 | 2005-03-31 | Astrazeneca Ab | Quinazoline derivatives |
| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| BRPI0414735A (pt) * | 2003-09-25 | 2006-11-21 | Astrazeneca Ab | derivado de quinazolina, composto, composição farmacêutica, uso de derivado de quinazolina, método para produzir um efeito anti-proliferativo em um animal de sangue quente, e, processo para a preparação de um derivado de quinazolina |
| MXPA06004304A (es) * | 2003-10-24 | 2006-06-05 | Hoffmann La Roche | Antagonistas del receptor ccr-3. |
| GB0326459D0 (en) * | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| CA2546002C (en) * | 2003-11-20 | 2012-09-18 | Janssen Pharmaceutica N.V. | 7-phenylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors |
| CA2546300C (en) | 2003-11-20 | 2012-10-02 | Janssen Pharmaceutica N.V. | 6-alkenyl and 6-phenylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors |
| JP4806353B2 (ja) * | 2003-12-05 | 2011-11-02 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ポリ（ａｄｐ−リボース）ポリメラーゼインヒビターとしての６−置換２−キノリノンおよび２−キノキサリノン |
| EP1713781B1 (en) * | 2004-02-03 | 2008-11-05 | AstraZeneca AB | Quinazoline derivatives |
| CN1993349A (zh) * | 2004-06-04 | 2007-07-04 | 阿斯利康(瑞典)有限公司 | 作为erbb受体酪氨酸激酶的喹唑啉衍生物 |
| ES2563954T3 (es) * | 2004-06-30 | 2016-03-16 | Janssen Pharmaceutica Nv | Derivados de ftalazina como inhibidores de PARP |
| CN1980913B (zh) | 2004-06-30 | 2011-12-14 | 詹森药业有限公司 | 作为parp抑制剂的喹唑啉二酮衍生物 |
| MXPA06014543A (es) * | 2004-06-30 | 2007-03-23 | Janssen Pharmaceutica Nv | Derivados de quinazolinona como inhibidores de la poli(adp-ribosa)polimerasa-i. |
| ATE501148T1 (de) | 2004-12-14 | 2011-03-15 | Astrazeneca Ab | Pyrazolopyrimidinverbindungen als antitumormittel |
| US8735410B2 (en) * | 2005-02-26 | 2014-05-27 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| EP1928861B1 (en) * | 2005-09-20 | 2010-11-17 | AstraZeneca AB | 4- (ih-indazol-5-yl-amino)-quinazoline compounds as erbb receptor tyrosine kinase inhibitors for the treatment of cancer |
| JP2009508917A (ja) * | 2005-09-20 | 2009-03-05 | アストラゼネカ アクチボラグ | 抗癌剤としてのキナゾリン誘導体 |
| US20090029968A1 (en) * | 2005-12-02 | 2009-01-29 | Bernard Christophe Barlaam | Quinazoline derivatives used as inhibitors of erbb tyrosine kinase |
| WO2007063291A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| EP1921070A1 (de) * | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| MX2009007610A (es) * | 2007-02-06 | 2009-07-24 | Boehringer Ingelheim Int | Heterociclicos biciclicos, medicamentos que contienen estos compuestos, su utilizacion y procedimientos para su preparacion. |
| WO2008107478A1 (en) | 2007-03-08 | 2008-09-12 | Janssen Pharmaceutica Nv | Quinolinone derivatives as parp and tank inhibitors |
| JP5525447B2 (ja) * | 2007-10-26 | 2014-06-18 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｐａｒｐ阻害剤としてのキノリノン誘導体 |
| WO2009098061A1 (de) * | 2008-02-07 | 2009-08-13 | Boehringer Ingelheim International Gmbh | Spirocyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| JP5464609B2 (ja) * | 2008-03-27 | 2014-04-09 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | チューブリン重合阻害剤としてのキナゾリノン誘導体 |
| WO2009118382A1 (en) | 2008-03-27 | 2009-10-01 | Janssen Pharmaceutica Nv | Tetrahydrophenanthridinones and tetrahydrocyclopentaquinolinones as parp and tubulin polymerization inhibitors |
| NZ589883A (en) | 2008-05-13 | 2012-06-29 | Astrazeneca Ab | Fumarate salt of 4- (3-chloro-2-fluoroanilino) -7-methoxy-6- { [1- (n-methylcarbamoylmethyl) piperidin- 4-yl] oxy} quinazoline |
| JP5539351B2 (ja) * | 2008-08-08 | 2014-07-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | シクロヘキシルオキシ置換ヘテロ環、これらの化合物を含有する医薬、およびそれらを生成するための方法 |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| CU24130B1 (es) | 2009-12-22 | 2015-09-29 | Novartis Ag | Isoquinolinonas y quinazolinonas sustituidas |
| BRPI1003506B1 (pt) | 2010-09-24 | 2019-12-03 | Ache Int Bvi Ltd | composto alquil-piperazino-fenil-4(3h)quinazolinonas e uso do composto alquil-piperazino-fenil-4(3h)quinazolinonas associado aos receptores serotoninérgicos 5-ht1a e 5-ht2a |
| JP6171003B2 (ja) | 2012-05-24 | 2017-07-26 | ノバルティス アーゲー | ピロロピロリジノン化合物 |
| EP2948451B1 (en) | 2013-01-22 | 2017-07-12 | Novartis AG | Substituted purinone compounds |
| EP2948453B1 (en) | 2013-01-22 | 2017-08-02 | Novartis AG | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the p53/mdm2 interaction |
| EP3412675A1 (en) | 2013-05-27 | 2018-12-12 | Novartis AG | Imidazopyrrolidinone derivatives and their use in the treatment of disease |
| US9624247B2 (en) | 2013-05-28 | 2017-04-18 | Novartis Ag | Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease |
| PT3004112T (pt) | 2013-05-28 | 2017-12-11 | Novartis Ag | Derivados de pirazolo-pirrolidin-4-ona e sua utilização no tratamento de doença |
| CN105916857B (zh) | 2013-11-21 | 2018-06-22 | 诺华股份有限公司 | 吡咯并吡咯酮衍生物及其作为bet抑制剂的用途 |
| WO2017003724A1 (en) | 2015-07-01 | 2017-01-05 | Crinetics Pharmaceuticals, Inc. | Somatostatin modulators and uses thereof |
| CN106866625B (zh) * | 2017-01-17 | 2019-12-13 | 上海鼎雅药物化学科技有限公司 | 酮色林的制备方法 |
| WO2019023278A1 (en) | 2017-07-25 | 2019-01-31 | Crinetics Pharmaceuticals, Inc. | MODULATORS OF SOMATOSTATIN AND USES THEREOF |
| CN109157507A (zh) * | 2018-09-14 | 2019-01-08 | 上海禾丰制药有限公司 | 酒石酸酮色林注射液及其制备方法 |
| CN112142760A (zh) * | 2020-10-20 | 2020-12-29 | 江苏法安德医药科技有限公司 | 一种酮色林中间体以及酮色林的制备方法 |
| WO2023133524A1 (en) * | 2022-01-06 | 2023-07-13 | Terran Biosciences, Inc. | A process for synthesizing ketanserin |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 DE DE8080300059T patent/DE3065489D1/de not_active Expired
- 1980-01-07 HU HU8025A patent/HU184222B/hu unknown
- 1980-01-07 FI FI800047A patent/FI66609C/fi not_active IP Right Cessation
- 1980-01-07 NO NO800034A patent/NO155243C/no unknown
- 1980-01-07 IL IL59084A patent/IL59084A/xx unknown
- 1980-01-07 SU SU802863403A patent/SU1041034A3/ru active
- 1980-01-07 CS CS80157A patent/CS223977B2/cs unknown
- 1980-01-07 PL PL1980221249A patent/PL125789B1/pl unknown
- 1980-01-07 EP EP80300059A patent/EP0013612B1/en not_active Expired
- 1980-01-07 IE IE21/80A patent/IE49351B1/en not_active IP Right Cessation
- 1980-01-07 AU AU54381/80A patent/AU536175B2/en not_active Expired
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- 1980-01-07 LU LU88219C patent/LU88219I2/xx unknown
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- 1980-01-07 AT AT80300059T patent/ATE5258T1/de not_active IP Right Cessation
- 1980-01-07 JP JP18680A patent/JPS55105679A/ja active Granted
- 1980-01-07 CA CA343,181A patent/CA1132557A/en not_active Expired
- 1980-01-07 ZA ZA00800082A patent/ZA8082B/xx unknown
- 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 PH PH23489A patent/PH17114A/en unknown
- 1980-01-08 YU YU46/80A patent/YU42957B/xx unknown
- 1980-01-21 KR KR1019800000201A patent/KR850000684B1/ko active
- 1980-02-20 RO RO80100248A patent/RO79148A/ro unknown
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1984
- 1984-07-06 SG SG486/84A patent/SG48684G/en unknown
- 1984-08-02 KR KR1019840004608A patent/KR850000677B1/ko not_active IP Right Cessation
- 1984-10-11 HK HK762/84A patent/HK76284A/xx not_active IP Right Cessation
- 1984-12-20 KR KR1019840008162A patent/KR850000683B1/ko not_active IP Right Cessation
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1987
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1993
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: JANSSEN PHARMACEUTICA N.V. |