ZA200309042B - Quinazoline derivatives which promote the release of parathyroid hormone. - Google Patents
Quinazoline derivatives which promote the release of parathyroid hormone. Download PDFInfo
- Publication number
- ZA200309042B ZA200309042B ZA200309042A ZA200309042A ZA200309042B ZA 200309042 B ZA200309042 B ZA 200309042B ZA 200309042 A ZA200309042 A ZA 200309042A ZA 200309042 A ZA200309042 A ZA 200309042A ZA 200309042 B ZA200309042 B ZA 200309042B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- isopropyl
- quinazolin
- lower alkyl
- formula
- Prior art date
Links
- 102000003982 Parathyroid hormone Human genes 0.000 title claims description 14
- 108090000445 Parathyroid hormone Proteins 0.000 title claims description 14
- 239000000199 parathyroid hormone Substances 0.000 title claims description 14
- 229960001319 parathyroid hormone Drugs 0.000 title claims description 14
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 116
- -1 loweralkynyl Chemical group 0.000 claims description 106
- 150000001875 compounds Chemical class 0.000 claims description 80
- 239000003795 chemical substances by application Substances 0.000 claims description 43
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 125000005843 halogen group Chemical group 0.000 claims description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 150000002148 esters Chemical class 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 210000000988 bone and bone Anatomy 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 9
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 9
- 230000008878 coupling Effects 0.000 claims description 9
- 238000010168 coupling process Methods 0.000 claims description 9
- 238000005859 coupling reaction Methods 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 8
- 230000001737 promoting effect Effects 0.000 claims description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 8
- 239000011575 calcium Substances 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 230000011164 ossification Effects 0.000 claims description 7
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 claims description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- 206010006956 Calcium deficiency Diseases 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- 238000005804 alkylation reaction Methods 0.000 claims description 6
- 125000005002 aryl methyl group Chemical group 0.000 claims description 6
- 229910052791 calcium Inorganic materials 0.000 claims description 6
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 239000002243 precursor Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 230000000638 stimulation Effects 0.000 claims description 6
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 230000029936 alkylation Effects 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 4
- 238000005576 amination reaction Methods 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 4
- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical compound O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 claims description 3
- OZQLEAQCIQBJDA-UHFFFAOYSA-N 1-(cyclohexylmethyl)-6,7-dimethoxy-4-(4-propan-2-ylphenyl)quinazolin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2C(C=2C=CC(=CC=2)C(C)C)=NC(=O)N1CC1CCCCC1 OZQLEAQCIQBJDA-UHFFFAOYSA-N 0.000 claims description 2
- NGXSFBCFLIAENV-UHFFFAOYSA-N 1-(furan-2-ylmethyl)-6-nitro-4-phenylquinazolin-2-one Chemical compound O=C1N=C(C=2C=CC=CC=2)C2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CO1 NGXSFBCFLIAENV-UHFFFAOYSA-N 0.000 claims description 2
- ALRFYFLWLWSCKJ-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]-6,7-dimethoxy-4-(4-propan-2-ylphenyl)quinazolin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2C(C=2C=CC(=CC=2)C(C)C)=NC(=O)N1CC1=CC=CC=C1F ALRFYFLWLWSCKJ-UHFFFAOYSA-N 0.000 claims description 2
- XXGORQGEJBODGD-UHFFFAOYSA-N 1-[(2-hydroxyphenyl)methyl]-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound C1=CC(C(C)C)=CC=C1C(C1=CC(OCC#C)=CC=C11)=NC(=O)N1CC1=CC=CC=C1O XXGORQGEJBODGD-UHFFFAOYSA-N 0.000 claims description 2
- IUKAZTOCWYYOFU-UHFFFAOYSA-N 1-[(2-hydroxyphenyl)methyl]-6,7-dimethoxy-4-(4-propan-2-ylphenyl)quinazolin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2C(C=2C=CC(=CC=2)C(C)C)=NC(=O)N1CC1=CC=CC=C1O IUKAZTOCWYYOFU-UHFFFAOYSA-N 0.000 claims description 2
- QANGLGODWVGURB-UHFFFAOYSA-N 1-[(3-hydroxyphenyl)methyl]-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound C1=CC(C(C)C)=CC=C1C(C1=CC(OCC#C)=CC=C11)=NC(=O)N1CC1=CC=CC(O)=C1 QANGLGODWVGURB-UHFFFAOYSA-N 0.000 claims description 2
- QTRNIOXDTOAYBF-UHFFFAOYSA-N 1-[[2-(6-imidazol-1-ylhexoxy)phenyl]methyl]-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound C1=CC(C(C)C)=CC=C1C(C1=CC(OCC#C)=CC=C11)=NC(=O)N1CC1=CC=CC=C1OCCCCCCN1C=NC=C1 QTRNIOXDTOAYBF-UHFFFAOYSA-N 0.000 claims description 2
- QKQDJYPQUARWEL-UHFFFAOYSA-N 1-[[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]phenyl]methyl]-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound COCCOCCOCCOC1=CC=CC=C1CN1C(=O)N=C(C=2C=CC(=CC=2)C(C)C)C2=CC(OCC#C)=CC=C21 QKQDJYPQUARWEL-UHFFFAOYSA-N 0.000 claims description 2
- AMLKCBXPVBOXAU-UHFFFAOYSA-N 1-[[3-(2-hydroxyethoxy)phenyl]methyl]-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound C1=CC(C(C)C)=CC=C1C(C1=CC(OCC#C)=CC=C11)=NC(=O)N1CC1=CC=CC(OCCO)=C1 AMLKCBXPVBOXAU-UHFFFAOYSA-N 0.000 claims description 2
- TUHIUWRABNYGEQ-UHFFFAOYSA-N 1-[[3-[2-(2-methoxyethoxy)ethoxy]phenyl]methyl]-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound COCCOCCOC1=CC=CC(CN2C(N=C(C3=CC(OCC#C)=CC=C32)C=2C=CC(=CC=2)C(C)C)=O)=C1 TUHIUWRABNYGEQ-UHFFFAOYSA-N 0.000 claims description 2
- OWWYZJFKHPNBBU-UHFFFAOYSA-N 1-[[3-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]phenyl]methyl]-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound COCCOCCOCCOC1=CC=CC(CN2C(N=C(C3=CC(OCC#C)=CC=C32)C=2C=CC(=CC=2)C(C)C)=O)=C1 OWWYZJFKHPNBBU-UHFFFAOYSA-N 0.000 claims description 2
- IUGDOAHHRSWINI-UHFFFAOYSA-N 1-benzyl-4-(3-chloro-4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one Chemical compound C1=C(Cl)C(C(C)C)=CC=C1C(C1=CC(OCC#C)=CC=C11)=NC(=O)N1CC1=CC=CC=C1 IUGDOAHHRSWINI-UHFFFAOYSA-N 0.000 claims description 2
- HQACTZJXOWFQGB-UHFFFAOYSA-N 1-benzyl-6-nitro-4-phenylquinazolin-2-one Chemical compound O=C1N=C(C=2C=CC=CC=2)C2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 HQACTZJXOWFQGB-UHFFFAOYSA-N 0.000 claims description 2
- ORDNSHRYPJOLOS-UHFFFAOYSA-N 2-[4-(2-methoxyethyl)piperazin-1-yl]-n-[3-[[2-oxo-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-1-yl]methyl]phenyl]acetamide Chemical compound C1CN(CCOC)CCN1CC(=O)NC1=CC=CC(CN2C(N=C(C3=CC(OCC#C)=CC=C32)C=2C=CC(=CC=2)C(C)C)=O)=C1 ORDNSHRYPJOLOS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- WJXFXVTYWJNFFA-UHFFFAOYSA-N 6-nitro-4-phenyl-1-(pyridin-2-ylmethyl)quinazolin-2-one Chemical compound O=C1N=C(C=2C=CC=CC=2)C2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=N1 WJXFXVTYWJNFFA-UHFFFAOYSA-N 0.000 claims description 2
- XTIZUTQBXFZEAW-UHFFFAOYSA-N 6-nitro-4-phenyl-1-(thiophen-2-ylmethyl)quinazolin-2-one Chemical compound O=C1N=C(C=2C=CC=CC=2)C2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CS1 XTIZUTQBXFZEAW-UHFFFAOYSA-N 0.000 claims description 2
- 125000006323 alkenyl amino group Chemical group 0.000 claims description 2
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000006319 alkynyl amino group Chemical group 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- FVACZQHQBKPPMX-UHFFFAOYSA-N quinazolin-2-one Chemical compound C1=C[CH]C2=NC(=O)N=CC2=C1 FVACZQHQBKPPMX-UHFFFAOYSA-N 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- SCGDDMDYSQTMGW-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-n-[3-[[2-oxo-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-1-yl]methyl]phenyl]acetamide Chemical compound C1=CC(C(C)C)=CC=C1C(C1=CC(OCC#C)=CC=C11)=NC(=O)N1CC1=CC=CC(NC(=O)CN2CCN(C)CC2)=C1 SCGDDMDYSQTMGW-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 42
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- 230000015572 biosynthetic process Effects 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
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- 238000010438 heat treatment Methods 0.000 description 9
- 239000012043 crude product Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000010626 work up procedure Methods 0.000 description 8
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000003810 Jones reagent Substances 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
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- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
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- 238000000746 purification Methods 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- WNYUUNBIOJZMSE-UHFFFAOYSA-N (3-methoxyphenyl)-(4-propan-2-ylphenyl)methanone Chemical compound COC1=CC=CC(C(=O)C=2C=CC(=CC=2)C(C)C)=C1 WNYUUNBIOJZMSE-UHFFFAOYSA-N 0.000 description 3
- BIEXCZDNZZTCST-UHFFFAOYSA-N (5-methoxy-2-nitrophenyl)-(4-propan-2-ylphenyl)methanone Chemical compound COC1=CC=C([N+]([O-])=O)C(C(=O)C=2C=CC(=CC=2)C(C)C)=C1 BIEXCZDNZZTCST-UHFFFAOYSA-N 0.000 description 3
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 3
- AQBZCTHAHIVXDI-UHFFFAOYSA-N 1-(4-methoxyphenyl)-1-propan-2-ylurea Chemical compound COC1=CC=C(N(C(C)C)C(N)=O)C=C1 AQBZCTHAHIVXDI-UHFFFAOYSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 3
- ZVAXFKMPKLESSD-UHFFFAOYSA-N 4-methoxy-n-propan-2-ylaniline Chemical compound COC1=CC=C(NC(C)C)C=C1 ZVAXFKMPKLESSD-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 150000008366 benzophenones Chemical class 0.000 description 3
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- WTWBUQJHJGUZCY-UHFFFAOYSA-N cuminaldehyde Chemical compound CC(C)C1=CC=C(C=O)C=C1 WTWBUQJHJGUZCY-UHFFFAOYSA-N 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
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Classifications
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- A61P9/12—Antihypertensives
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/88—Nicotinoylhydrazones
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- 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
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
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- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
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- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
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- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GB0114702A GB0114702D0 (en) | 2001-06-15 | 2001-06-15 | Organic compounds |
GB0114701A GB0114701D0 (en) | 2001-06-15 | 2001-06-15 | Organic compounds |
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ZA200309042B true ZA200309042B (en) | 2004-05-21 |
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ZA200309042A ZA200309042B (en) | 2001-06-15 | 2003-11-20 | Quinazoline derivatives which promote the release of parathyroid hormone. |
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US (1) | US8476286B2 (cs) |
EP (2) | EP1401451B1 (cs) |
JP (2) | JP4118801B2 (cs) |
KR (1) | KR100699959B1 (cs) |
CN (1) | CN1516587A (cs) |
AR (1) | AR038658A1 (cs) |
AT (1) | ATE447958T1 (cs) |
AU (1) | AU2002325242B2 (cs) |
BR (1) | BR0210920A (cs) |
CA (1) | CA2449234C (cs) |
CO (1) | CO5550443A2 (cs) |
CY (1) | CY1109767T1 (cs) |
CZ (1) | CZ20033389A3 (cs) |
DE (1) | DE60234341D1 (cs) |
DK (1) | DK1401451T3 (cs) |
ES (1) | ES2336197T3 (cs) |
HU (1) | HUP0400205A3 (cs) |
IL (2) | IL159000A0 (cs) |
MX (1) | MXPA03011626A (cs) |
MY (1) | MY145325A (cs) |
NO (1) | NO326384B1 (cs) |
NZ (1) | NZ529716A (cs) |
PE (1) | PE20030121A1 (cs) |
PL (1) | PL364474A1 (cs) |
PT (1) | PT1401451E (cs) |
RU (1) | RU2302244C2 (cs) |
SI (1) | SI1401451T1 (cs) |
SK (1) | SK287802B6 (cs) |
TW (1) | TWI330179B (cs) |
WO (1) | WO2002102782A2 (cs) |
ZA (1) | ZA200309042B (cs) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR038658A1 (es) | 2001-06-15 | 2005-01-26 | Novartis Ag | Derivados de 4-aril-2(1h) quinazolinona y 4-aril-quinazolina 2-sustituidas, un proceso para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la preparacion de un medicamento |
GB0230015D0 (en) * | 2002-12-23 | 2003-01-29 | Novartis Ag | Organic compounds |
AU2007231842B2 (en) * | 2002-12-23 | 2011-04-14 | Novartis Ag | Derivatives of aryl-quinazoline/aryl-2-amino-phenyl methanone which promote the release of parathyroid hormone |
ATE452121T1 (de) | 2003-04-23 | 2010-01-15 | Japan Tobacco Inc | Casr-antagonist |
DE102005022977A1 (de) | 2005-05-19 | 2006-12-07 | Merck Patent Gmbh | Phenylchinazolinderivate |
GB0511410D0 (en) * | 2005-06-03 | 2005-07-13 | James Black Foundation | Benzotrizepinone derivatives |
GB0516723D0 (en) * | 2005-08-15 | 2005-09-21 | Novartis Ag | Organic compounds |
GB0610018D0 (en) * | 2006-05-19 | 2006-06-28 | James Black Foundation | Benzotriazepinone derivatives |
KR100974081B1 (ko) * | 2008-07-24 | 2010-08-04 | 이화여자대학교 산학협력단 | 착탈식 치아 교정기구 |
JP5643233B2 (ja) * | 2009-02-10 | 2014-12-17 | 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Janssen Pharmaceutica Naamloze Vennootschap | プロリルヒドロキシラーゼ阻害物質としてのキナゾリノン |
ES2525353T3 (es) | 2009-04-28 | 2014-12-22 | Chugai Seiyaku Kabushiki Kaisha | Derivado de espiroimidazolona |
AU2012328763A1 (en) | 2011-10-25 | 2014-05-01 | Janssen Pharmaceutica Nv | Meglumine salt formulations of 1-(5,6-dichloro-1H-benzo(d)imidazol-2-yl)-1H-pyrazole-4-carboxylic acid |
MA38250B1 (fr) * | 2012-12-10 | 2017-10-31 | Chugai Pharmaceutical Co Ltd | Nouveau dérivés d'hydantoïne pour leurs utilisations dans le traitement de maladies, comme l'osteoporose et la thrombocytopenie |
CA2949023C (en) | 2014-06-09 | 2021-10-12 | Hiroshi Noda | Hydantoin derivative-containing pharmaceutical composition |
US20230257359A1 (en) * | 2020-06-10 | 2023-08-17 | Ideaya Biosciences, Inc. | 4-arylquinazoline derivatives as methionine adenosyltransferase 2a inhibitors |
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JPS518287A (en) | 1974-07-13 | 1976-01-23 | Sumitomo Chemical Co | Kinazorinonjudotaioyobi sonoenno seizoho |
JPS5125193A (en) * | 1974-08-26 | 1976-03-01 | Sumitomo Chemical Co | Kinazorinjudotaino biryoteiryoho |
JPS5251379A (en) | 1975-10-24 | 1977-04-25 | Sumitomo Chem Co Ltd | Preparation 3,4-dihydro-2(1h)-quinazoline derivates |
JPS5271483A (en) * | 1975-12-11 | 1977-06-14 | Sumitomo Chem Co Ltd | Synthesis of 2(1h)-quinazolinone derivatives |
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JPS5795966A (en) | 1980-12-04 | 1982-06-15 | Sumitomo Chem Co Ltd | Novel 2(1h)-quinazolinone derivative |
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US5773663A (en) | 1996-05-01 | 1998-06-30 | American Cyanamid Company | Fungicidal methods, compounds and compositions containing benzophenones |
DE19524398C1 (de) * | 1995-07-04 | 1996-11-21 | Adalbert Gubo | Verfahren zum Archivieren von Dokumenten |
CN1136547C (zh) | 1995-08-22 | 2004-01-28 | 松下电器产业株式会社 | 光盘记录和/或重放装置及设定记录功率及清除功率的方法 |
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JP4974437B2 (ja) | 2000-09-25 | 2012-07-11 | 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 | ファルネシルトランスフェラーゼを阻害する6−[(置換フェニル)メチル]−キノリンおよびキナゾリン誘導体 |
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AR038658A1 (es) * | 2001-06-15 | 2005-01-26 | Novartis Ag | Derivados de 4-aril-2(1h) quinazolinona y 4-aril-quinazolina 2-sustituidas, un proceso para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la preparacion de un medicamento |
GB0230015D0 (en) | 2002-12-23 | 2003-01-29 | Novartis Ag | Organic compounds |
US7776035B2 (en) * | 2004-10-08 | 2010-08-17 | Covidien Ag | Cool-tip combined electrode introducer |
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