JP2005526070A - オキソ−アザ二環系化合物 - Google Patents
オキソ−アザ二環系化合物 Download PDFInfo
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- JP2005526070A JP2005526070A JP2003574636A JP2003574636A JP2005526070A JP 2005526070 A JP2005526070 A JP 2005526070A JP 2003574636 A JP2003574636 A JP 2003574636A JP 2003574636 A JP2003574636 A JP 2003574636A JP 2005526070 A JP2005526070 A JP 2005526070A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 393
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 38
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 29
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 25
- 239000002253 acid Substances 0.000 claims abstract description 23
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 19
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 19
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 11
- 150000007513 acids Chemical class 0.000 claims abstract description 10
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 80
- -1 hydroxy, cyano, tetrazolyl Chemical group 0.000 claims description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- 238000004519 manufacturing process Methods 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 27
- 230000003197 catalytic effect Effects 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
- 239000011593 sulfur Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 238000000926 separation method Methods 0.000 claims description 13
- 239000007858 starting material Substances 0.000 claims description 13
- 125000002619 bicyclic group Chemical group 0.000 claims description 12
- 201000008482 osteoarthritis Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000004434 sulfur atom Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 11
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 11
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 10
- ICGYHHIJQXSEQH-UHFFFAOYSA-N 4-[[4-oxo-6-(3-phenylprop-1-ynyl)quinazolin-3-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=CC=C2N=C1 ICGYHHIJQXSEQH-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 8
- 206010003246 arthritis Diseases 0.000 claims description 7
- 208000002780 macular degeneration Diseases 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
- 208000001132 Osteoporosis Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 6
- 208000028169 periodontal disease Diseases 0.000 claims description 6
- OJHFOZDTLSSJAG-UHFFFAOYSA-N 3-[(3-fluorophenyl)methyl]-n-[(3-methoxyphenyl)methyl]-4-oxopyrido[3,4-d]pyrimidine-6-carboxamide Chemical compound COC1=CC=CC(CNC(=O)C=2N=CC3=C(C(N(CC=4C=C(F)C=CC=4)C=N3)=O)C=2)=C1 OJHFOZDTLSSJAG-UHFFFAOYSA-N 0.000 claims description 5
- HGWNWHHVVVGHQI-UHFFFAOYSA-N 4-[[6-[3-(4-methoxyphenyl)prop-1-ynyl]-4-oxoquinazolin-3-yl]methyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1CC#CC1=CC=C(N=CN(CC=2C=CC(=CC=2)C(O)=O)C2=O)C2=C1 HGWNWHHVVVGHQI-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- GWHYYUGLKSZLLD-UHFFFAOYSA-N 3-[(3-fluorophenyl)methyl]-n-[(4-methoxyphenyl)methyl]-4-oxopyrido[3,4-d]pyrimidine-6-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC(C(N(CC=2C=C(F)C=CC=2)C=N2)=O)=C2C=N1 GWHYYUGLKSZLLD-UHFFFAOYSA-N 0.000 claims description 4
- FBQYESDSNNRJGM-UHFFFAOYSA-N 4-[[4-oxo-6-(3-phenylprop-1-ynyl)pyrido[3,4-d]pyrimidin-3-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=NC=C2N=C1 FBQYESDSNNRJGM-UHFFFAOYSA-N 0.000 claims description 4
- JEAAFRYXYNTZGQ-UHFFFAOYSA-N 4-[[6-[(3-methoxyphenyl)methylcarbamoyl]-4-oxoquinazolin-3-yl]methyl]benzoic acid Chemical compound COC1=CC=CC(CNC(=O)C=2C=C3C(=O)N(CC=4C=CC(=CC=4)C(O)=O)C=NC3=CC=2)=C1 JEAAFRYXYNTZGQ-UHFFFAOYSA-N 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000004678 hydrides Chemical class 0.000 claims description 4
- PSFGVWUWJYYRGT-UHFFFAOYSA-N n-[4-[[4-oxo-6-(3-phenylprop-1-ynyl)quinazolin-3-yl]methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=CC=C2N=C1 PSFGVWUWJYYRGT-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- OQNYIKRMHGRDIQ-UHFFFAOYSA-N 3-[(4-acetylphenyl)methyl]-6-[3-(4-methoxyphenyl)prop-1-ynyl]quinazolin-4-one Chemical compound C1=CC(OC)=CC=C1CC#CC1=CC=C(N=CN(CC=2C=CC(=CC=2)C(C)=O)C2=O)C2=C1 OQNYIKRMHGRDIQ-UHFFFAOYSA-N 0.000 claims description 3
- NWSMPZQPOPCBQU-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-6-(3-phenylprop-1-ynyl)pyrido[3,4-d]pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=NC=C2N=C1 NWSMPZQPOPCBQU-UHFFFAOYSA-N 0.000 claims description 3
- BTVFBQCKHQGEQX-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-6-(3-phenylprop-1-ynyl)quinazolin-4-one Chemical compound C1=CC(F)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=CC=C2N=C1 BTVFBQCKHQGEQX-UHFFFAOYSA-N 0.000 claims description 3
- AURPLPVPCDLQBS-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-n-[(2-methoxypyridin-4-yl)methyl]-4-oxoquinazoline-6-carboxamide Chemical compound C1=NC(OC)=CC(CNC(=O)C=2C=C3C(=O)N(CC=4C=CC(F)=CC=4)C=NC3=CC=2)=C1 AURPLPVPCDLQBS-UHFFFAOYSA-N 0.000 claims description 3
- ZQVGPQMOIOLUQX-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-n-[(3-methoxyphenyl)methyl]-4-oxoquinazoline-6-carboxamide Chemical compound COC1=CC=CC(CNC(=O)C=2C=C3C(=O)N(CC=4C=CC(F)=CC=4)C=NC3=CC=2)=C1 ZQVGPQMOIOLUQX-UHFFFAOYSA-N 0.000 claims description 3
- AOWUKXFBPGVBDW-UHFFFAOYSA-N 4-[[4-oxo-6-(3-phenylprop-1-ynyl)quinazolin-3-yl]methyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=CC=C2N=C1 AOWUKXFBPGVBDW-UHFFFAOYSA-N 0.000 claims description 3
- RCZSEZGNROFIGF-UHFFFAOYSA-N 4-[[4-oxo-6-(3-phenylprop-1-ynyl)quinazolin-3-yl]methyl]benzonitrile Chemical compound C1=NC2=CC=C(C#CCC=3C=CC=CC=3)C=C2C(=O)N1CC1=CC=C(C#N)C=C1 RCZSEZGNROFIGF-UHFFFAOYSA-N 0.000 claims description 3
- XOJGZFAHUIZIPI-UHFFFAOYSA-N 4-[[6-(3-imidazol-1-ylprop-1-ynyl)-4-oxoquinazolin-3-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1C(=O)C2=CC(C#CCN3C=NC=C3)=CC=C2N=C1 XOJGZFAHUIZIPI-UHFFFAOYSA-N 0.000 claims description 3
- CVDUNSMZBHDGHM-UHFFFAOYSA-N 4-[[6-[(4-methoxyphenyl)methylcarbamoyl]-1-methyl-4-oxo-2h-quinazolin-3-yl]methyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(N(C)CN(CC=2C=CC(=CC=2)C(O)=O)C2=O)C2=C1 CVDUNSMZBHDGHM-UHFFFAOYSA-N 0.000 claims description 3
- AKFOYYXBYKQZDK-UHFFFAOYSA-N 6-(3-phenylprop-1-ynyl)-3-(pyridin-4-ylmethyl)quinazolin-4-one Chemical compound C1=NC2=CC=C(C#CCC=3C=CC=CC=3)C=C2C(=O)N1CC1=CC=NC=C1 AKFOYYXBYKQZDK-UHFFFAOYSA-N 0.000 claims description 3
- FWRSYWBCZFQNKX-UHFFFAOYSA-N 6-(3-phenylprop-1-ynyl)-3-[[4-(2h-tetrazol-5-yl)phenyl]methyl]quinazolin-4-one Chemical compound C1=NC2=CC=C(C#CCC=3C=CC=CC=3)C=C2C(=O)N1CC(C=C1)=CC=C1C1=NN=NN1 FWRSYWBCZFQNKX-UHFFFAOYSA-N 0.000 claims description 3
- JTKHBRCNEGBAOH-UHFFFAOYSA-N 6-[3-(4-methoxyphenyl)prop-1-ynyl]-3-(pyridin-4-ylmethyl)quinazolin-4-one Chemical compound C1=CC(OC)=CC=C1CC#CC1=CC=C(N=CN(CC=2C=CN=CC=2)C2=O)C2=C1 JTKHBRCNEGBAOH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- HKGZBEPCCYMWCK-UHFFFAOYSA-N n,3-bis[(4-methoxyphenyl)methyl]-1,2,2-trimethyl-4-oxoquinazoline-6-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(N(C)C(C)(C)N(CC=2C=CC(OC)=CC=2)C2=O)C2=C1 HKGZBEPCCYMWCK-UHFFFAOYSA-N 0.000 claims description 3
- CREMAOVCPZRLIR-UHFFFAOYSA-N n,3-bis[(4-methoxyphenyl)methyl]-1-methyl-4-oxo-2h-quinazoline-6-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(N(C)CN(CC=2C=CC(OC)=CC=2)C2=O)C2=C1 CREMAOVCPZRLIR-UHFFFAOYSA-N 0.000 claims description 3
- XNTSHWMGQYMTPH-UHFFFAOYSA-N n,3-bis[(4-methoxyphenyl)methyl]-2-methyl-4-oxoquinazoline-6-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(N=C(C)N(CC=2C=CC(OC)=CC=2)C2=O)C2=C1 XNTSHWMGQYMTPH-UHFFFAOYSA-N 0.000 claims description 3
- DOADCMDDDNIBIH-UHFFFAOYSA-N n,3-bis[(4-methoxyphenyl)methyl]-4-oxoquinazoline-6-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(N=CN(CC=2C=CC(OC)=CC=2)C2=O)C2=C1 DOADCMDDDNIBIH-UHFFFAOYSA-N 0.000 claims description 3
- GWONXAQVMGMOOH-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-4-oxo-3-[(4-pyrrolidin-1-ylsulfonylphenyl)methyl]quinazoline-6-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(N=CN(CC=2C=CC(=CC=2)S(=O)(=O)N2CCCC2)C2=O)C2=C1 GWONXAQVMGMOOH-UHFFFAOYSA-N 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- UAYISHCOXCDESE-UHFFFAOYSA-N 3-[(3,4-difluorophenyl)methyl]-6-(3-phenylprop-1-ynyl)quinazolin-4-one Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=CC=C2N=C1 UAYISHCOXCDESE-UHFFFAOYSA-N 0.000 claims description 2
- FSDJUBMCBVPVIH-UHFFFAOYSA-N 3-[(3,4-difluorophenyl)methyl]-n-[(2-methoxypyridin-4-yl)methyl]-4-oxoquinazoline-6-carboxamide Chemical compound C1=NC(OC)=CC(CNC(=O)C=2C=C3C(=O)N(CC=4C=C(F)C(F)=CC=4)C=NC3=CC=2)=C1 FSDJUBMCBVPVIH-UHFFFAOYSA-N 0.000 claims description 2
- RHPUXMIIBYSTOZ-UHFFFAOYSA-N 3-[(3-chlorophenyl)methyl]-6-(4-phenylbut-1-ynyl)quinazolin-4-one Chemical compound ClC1=CC=CC(CN2C(C3=CC(=CC=C3N=C2)C#CCCC=2C=CC=CC=2)=O)=C1 RHPUXMIIBYSTOZ-UHFFFAOYSA-N 0.000 claims description 2
- IHAOAKQKZVQAQJ-UHFFFAOYSA-N 4-[[4-oxo-6-(3-phenylprop-1-ynyl)quinazolin-3-yl]methyl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=CC=C2N=C1 IHAOAKQKZVQAQJ-UHFFFAOYSA-N 0.000 claims description 2
- FLGQAENKZGTVFO-UHFFFAOYSA-N 4-[[4-oxo-6-(3-pyrazol-1-ylprop-1-ynyl)quinazolin-3-yl]methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1C(=O)C2=CC(C#CCN3N=CC=C3)=CC=C2N=C1 FLGQAENKZGTVFO-UHFFFAOYSA-N 0.000 claims description 2
- QPJVIYCYTOLCRY-UHFFFAOYSA-N 4-[[6-[(4-methoxyphenyl)methylcarbamoyl]-4-oxo-1,2-dihydroquinazolin-3-yl]methyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C(NCN(CC=2C=CC(=CC=2)C(O)=O)C2=O)C2=C1 QPJVIYCYTOLCRY-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 claims description 2
- 239000012190 activator Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 238000005905 alkynylation reaction Methods 0.000 claims description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 2
- 238000005266 casting Methods 0.000 claims description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- RHWQBDCMIUUGLN-UHFFFAOYSA-N methyl 4-[[4-oxo-6-(3-phenylprop-1-ynyl)quinazolin-3-yl]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C(=O)C2=CC(C#CCC=3C=CC=CC=3)=CC=C2N=C1 RHWQBDCMIUUGLN-UHFFFAOYSA-N 0.000 claims description 2
- LQOWVHDXZIRHGD-UHFFFAOYSA-N methyl 4-[[6-[(4-methoxyphenyl)methylcarbamoyl]-1-methyl-4-oxo-2h-quinazolin-3-yl]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C(=O)C2=CC(C(=O)NCC=3C=CC(OC)=CC=3)=CC=C2N(C)C1 LQOWVHDXZIRHGD-UHFFFAOYSA-N 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 239000003586 protic polar solvent Substances 0.000 claims description 2
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 3
- RCNNSSVVIZELDU-UHFFFAOYSA-N 3-[(3,4-difluorophenyl)methyl]-6-(3-pyridin-4-yloxyprop-1-ynyl)quinazolin-4-one Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)C2=CC(C#CCOC=3C=CN=CC=3)=CC=C2N=C1 RCNNSSVVIZELDU-UHFFFAOYSA-N 0.000 claims 1
- LYWCXUOOHZOGQT-UHFFFAOYSA-N 3-[(3,4-difluorophenyl)methyl]-6-[3-(4-methoxyphenyl)prop-1-ynyl]quinazolin-4-one Chemical compound C1=CC(OC)=CC=C1CC#CC1=CC=C(N=CN(CC=2C=C(F)C(F)=CC=2)C2=O)C2=C1 LYWCXUOOHZOGQT-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229940127554 medical product Drugs 0.000 claims 1
- 239000002585 base Substances 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 4
- 230000003287 optical effect Effects 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 2
- 239000013000 chemical inhibitor Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 41
- 238000005481 NMR spectroscopy Methods 0.000 description 40
- 238000002360 preparation method Methods 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 22
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (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)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2002/003240 WO2003076416A1 (en) | 2002-03-08 | 2002-03-08 | Oxo azabicyclic compounds |
| PCT/EP2003/002277 WO2003076417A2 (en) | 2002-03-08 | 2003-03-06 | Oxo-azabicyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2005526070A true JP2005526070A (ja) | 2005-09-02 |
Family
ID=27798761
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003574636A Withdrawn JP2005526070A (ja) | 2002-03-08 | 2003-03-06 | オキソ−アザ二環系化合物 |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP1492775A2 (xx) |
| JP (1) | JP2005526070A (xx) |
| KR (1) | KR20040095270A (xx) |
| CN (1) | CN1738806A (xx) |
| AP (1) | AP2004003125A0 (xx) |
| AR (1) | AR039562A1 (xx) |
| AU (2) | AU2002249275A1 (xx) |
| BR (1) | BR0308280A (xx) |
| CA (1) | CA2478706A1 (xx) |
| CO (1) | CO5601020A2 (xx) |
| EA (1) | EA200401053A1 (xx) |
| EC (1) | ECSP045278A (xx) |
| IL (1) | IL163818A0 (xx) |
| IS (1) | IS7414A (xx) |
| MA (1) | MA27183A1 (xx) |
| MX (1) | MXPA04008681A (xx) |
| NO (1) | NO20044041L (xx) |
| OA (1) | OA12782A (xx) |
| PA (1) | PA8568501A1 (xx) |
| PE (1) | PE20031018A1 (xx) |
| PL (1) | PL372622A1 (xx) |
| SV (1) | SV2003001495A (xx) |
| TN (1) | TNSN04169A1 (xx) |
| UY (1) | UY27700A1 (xx) |
| WO (2) | WO2003076416A1 (xx) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PA8539501A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Compuestos triazolo como inhibidores de mmp |
| US6962922B2 (en) | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| US6894057B2 (en) | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| WO2004014892A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Monocyclic derivatives as matrix metalloproteinase inhibitors |
| AU2003249539A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Cyclic compounds containing zinc binding groups as matrix metalloproteinase inhibitors |
| PA8578101A1 (es) | 2002-08-13 | 2004-05-07 | Warner Lambert Co | Derivados de heterobiarilo como inhibidores de metaloproteinasa de la matriz |
| AU2003250470A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Pyrimidinone fused bicyclic metalloproteinase inhibitors |
| EP1553949B1 (en) | 2002-08-13 | 2007-04-18 | Warner-Lambert Company LLC | Pyrimidine-2,4-dione derivatives as matrix metalloproteinase inhibitors |
| WO2004014378A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | 3-isoquinolinone derivatives as matrix metalloproteinase inhiitors |
| BR0313724A (pt) | 2002-08-13 | 2005-06-28 | Warner Lambert Co | Derivados de azaisoquinolina como inibidores de metaloproteinase de matriz |
| MXPA05001785A (es) | 2002-08-13 | 2005-04-25 | Warner Lambert Co | Derivados de cromona como inhibidores de las metaloproteinasas de matriz. |
| AU2003253186A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Fused tetrahydropyridine derivatives as matrix metalloproteinase inhibitors |
| WO2004014375A2 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Fused bicyclic metalloproteinase inhibitors |
| WO2005016926A1 (en) * | 2003-08-19 | 2005-02-24 | Warner-Lambert Company Llc | Pyrido [3,4-d] pyrimidine derivatives as matrix metalloproteinase-13 inhibitors |
| DE10360835A1 (de) * | 2003-12-23 | 2005-07-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Imidazolverbindungen, deren Herstellung und deren Verwendung als Arzneimittel |
| BRPI0510305A (pt) * | 2004-04-30 | 2007-10-02 | Takeda Pharmaceutical | composto ou um sal do mesmo, pródroga ou um sal da mesma, agente farmacêutico, método de produção do composto ou um sal do mesmo, inibidor de metaloproteinase de matriz ou um sal do mesmo ou uma pródroga do mesmo, método de inibir uma metaloproteinase de matriz, e, uso de um composto ou de um sal do mesmo ou de uma pródroga do mesmo |
| JP2008502666A (ja) * | 2004-06-15 | 2008-01-31 | アストラゼネカ アクチボラグ | 抗癌剤としての置換キナゾロン類 |
| CA2665476A1 (en) | 2006-10-05 | 2008-04-10 | Cv Therapeutics, Inc. | Bicyclic nitrogen-containing heterocyclic compounds for use as stearoyl coa desaturase inhibitors |
| AR083475A1 (es) | 2010-10-18 | 2013-02-27 | Merz Pharma Gmbh & Co Kgaa | Moduladores de receptores de glutamato metabotropicos |
| CN103524431B (zh) * | 2013-09-24 | 2016-01-13 | 西安交通大学 | 3-苄基-4-喹唑啉酮类化合物及其合成方法和应用 |
| JO3512B1 (ar) | 2014-03-26 | 2020-07-05 | Astex Therapeutics Ltd | مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز |
| HUE057090T2 (hu) | 2015-09-23 | 2022-04-28 | Janssen Pharmaceutica Nv | BI-heteroaril-szubsztituált 1,4-benzodiazepinek és alkalmazásuk rák kezelésében |
| BR112018005637B1 (pt) | 2015-09-23 | 2023-11-28 | Janssen Pharmaceutica Nv | Compostos derivados de quinoxalina, quinolina e quinazolinona,composições farmacêuticas que os compreende, e uso dos referidos compostos |
| FR3046793B1 (fr) * | 2016-01-14 | 2018-01-05 | Les Laboratoires Servier | Nouveaux derives de phosphinanes et azaphosphinanes, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU5380398A (en) * | 1996-12-17 | 1998-07-15 | E.I. Du Pont De Nemours And Company | Fungicidal quinazolinones |
| PA8539401A1 (es) * | 2001-02-14 | 2002-10-28 | Warner Lambert Co | Quinazolinas como inhibidores de mmp-13 |
| PA8539301A1 (es) * | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Inhibidores de la metaloproteinasa de la matriz |
-
2002
- 2002-03-08 WO PCT/EP2002/003240 patent/WO2003076416A1/en not_active Application Discontinuation
- 2002-03-08 AU AU2002249275A patent/AU2002249275A1/en not_active Abandoned
-
2003
- 2003-03-04 SV SV2003001495A patent/SV2003001495A/es not_active Application Discontinuation
- 2003-03-06 JP JP2003574636A patent/JP2005526070A/ja not_active Withdrawn
- 2003-03-06 KR KR10-2004-7013994A patent/KR20040095270A/ko not_active Application Discontinuation
- 2003-03-06 BR BR0308280-6A patent/BR0308280A/pt not_active IP Right Cessation
- 2003-03-06 CA CA002478706A patent/CA2478706A1/en not_active Abandoned
- 2003-03-06 MX MXPA04008681A patent/MXPA04008681A/es unknown
- 2003-03-06 AR ARP030100749A patent/AR039562A1/es not_active Application Discontinuation
- 2003-03-06 AU AU2003212307A patent/AU2003212307A1/en not_active Abandoned
- 2003-03-06 AP APAP/P/2004/003125A patent/AP2004003125A0/en unknown
- 2003-03-06 OA OA1200400234A patent/OA12782A/en unknown
- 2003-03-06 PA PA20038568501A patent/PA8568501A1/es unknown
- 2003-03-06 IL IL16381803A patent/IL163818A0/xx unknown
- 2003-03-06 CN CNA038048752A patent/CN1738806A/zh active Pending
- 2003-03-06 WO PCT/EP2003/002277 patent/WO2003076417A2/en not_active Application Discontinuation
- 2003-03-06 PE PE2003000218A patent/PE20031018A1/es not_active Application Discontinuation
- 2003-03-06 UY UY27700A patent/UY27700A1/es not_active Application Discontinuation
- 2003-03-06 EA EA200401053A patent/EA200401053A1/ru unknown
- 2003-03-06 EP EP03708181A patent/EP1492775A2/en not_active Withdrawn
- 2003-03-06 PL PL03372622A patent/PL372622A1/xx not_active Application Discontinuation
-
2004
- 2004-08-19 IS IS7414A patent/IS7414A/is unknown
- 2004-08-25 CO CO04082792A patent/CO5601020A2/es not_active Application Discontinuation
- 2004-08-31 MA MA27842A patent/MA27183A1/fr unknown
- 2004-09-03 EC EC2004005278A patent/ECSP045278A/es unknown
- 2004-09-03 TN TNP2004000169A patent/TNSN04169A1/fr unknown
- 2004-09-24 NO NO20044041A patent/NO20044041L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CO5601020A2 (es) | 2006-01-31 |
| AU2002249275A1 (en) | 2003-09-22 |
| WO2003076417A2 (en) | 2003-09-18 |
| CA2478706A1 (en) | 2003-09-18 |
| WO2003076417A3 (en) | 2003-11-13 |
| PL372622A1 (en) | 2005-07-25 |
| MXPA04008681A (es) | 2004-12-06 |
| IL163818A0 (en) | 2005-12-18 |
| TNSN04169A1 (fr) | 2007-03-12 |
| AR039562A1 (es) | 2005-02-23 |
| EA200401053A1 (ru) | 2005-04-28 |
| SV2003001495A (es) | 2003-11-04 |
| BR0308280A (pt) | 2004-12-28 |
| OA12782A (en) | 2006-07-10 |
| MA27183A1 (fr) | 2005-01-03 |
| PE20031018A1 (es) | 2004-01-09 |
| EP1492775A2 (en) | 2005-01-05 |
| NO20044041L (no) | 2004-10-07 |
| AP2004003125A0 (en) | 2004-09-30 |
| AU2003212307A1 (en) | 2003-09-22 |
| WO2003076416A1 (en) | 2003-09-18 |
| UY27700A1 (es) | 2003-10-31 |
| PA8568501A1 (es) | 2003-12-19 |
| IS7414A (is) | 2004-08-19 |
| ECSP045278A (es) | 2004-10-26 |
| CN1738806A (zh) | 2006-02-22 |
| KR20040095270A (ko) | 2004-11-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20060322 |