ES2239216T3 - Compuestos triazolo como inhibidores de mmp. - Google Patents
Compuestos triazolo como inhibidores de mmp.Info
- Publication number
- ES2239216T3 ES2239216T3 ES02702366T ES02702366T ES2239216T3 ES 2239216 T3 ES2239216 T3 ES 2239216T3 ES 02702366 T ES02702366 T ES 02702366T ES 02702366 T ES02702366 T ES 02702366T ES 2239216 T3 ES2239216 T3 ES 2239216T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- compound
- group
- formula
- oxygen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 297
- 229940124761 MMP inhibitor Drugs 0.000 title description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 105
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 85
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 76
- 239000001257 hydrogen Substances 0.000 claims abstract description 76
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 72
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 71
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 69
- 239000001301 oxygen Substances 0.000 claims abstract description 69
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 68
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 61
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 54
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 54
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 47
- 239000011593 sulfur Chemical group 0.000 claims abstract description 47
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 46
- 150000002367 halogens Chemical class 0.000 claims abstract description 45
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 33
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 33
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 29
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 20
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 15
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 22
- -1 benzodioxynil Chemical group 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 98
- 238000000034 method Methods 0.000 claims description 96
- 230000008569 process Effects 0.000 claims description 85
- 125000004429 atom Chemical group 0.000 claims description 44
- 239000002253 acid Substances 0.000 claims description 39
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 36
- 238000004519 manufacturing process Methods 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 22
- 239000011159 matrix material Substances 0.000 claims description 22
- 102000005741 Metalloproteases Human genes 0.000 claims description 19
- 108010006035 Metalloproteases Proteins 0.000 claims description 19
- 150000001204 N-oxides Chemical class 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 16
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 15
- 239000005711 Benzoic acid Substances 0.000 claims description 15
- 235000010233 benzoic acid Nutrition 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000001544 thienyl group Chemical group 0.000 claims description 15
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 claims description 14
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 14
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 14
- 125000002541 furyl group Chemical group 0.000 claims description 14
- 125000002883 imidazolyl group Chemical group 0.000 claims description 14
- 125000001041 indolyl group Chemical group 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 201000008482 osteoarthritis Diseases 0.000 claims description 11
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 claims description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 9
- 229940095102 methyl benzoate Drugs 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 8
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 8
- 150000002829 nitrogen Chemical group 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- TYHCBIKGTCZFTK-UHFFFAOYSA-N quinazoline-7-carboxamide Chemical compound C1=NC=NC2=CC(C(=O)N)=CC=C21 TYHCBIKGTCZFTK-UHFFFAOYSA-N 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 7
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- SRKXVESHUPPYMO-UHFFFAOYSA-N quinazoline-7-carboxylic acid Chemical compound C1=NC=NC2=CC(C(=O)O)=CC=C21 SRKXVESHUPPYMO-UHFFFAOYSA-N 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 150000003246 quinazolines Chemical class 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 239000012190 activator Substances 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
- 230000000414 obstructive effect Effects 0.000 claims description 3
- 208000028169 periodontal disease Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 230000002685 pulmonary effect Effects 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- CKDZEXUCUNHQIY-UHFFFAOYSA-N 2h-tetrazole-5-carbonitrile Chemical compound N#CC=1N=NNN=1 CKDZEXUCUNHQIY-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 229910052705 radium Inorganic materials 0.000 claims description 2
- VMSPJYJGWZXQDC-UHFFFAOYSA-N 2-[4-[[7-[(4-methoxyphenyl)methylcarbamoyl]-5-oxo-[1,2,4]triazolo[4,3-a]quinazolin-4-yl]methyl]phenyl]acetic acid Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC=C2N3C=NN=C3N(CC=3C=CC(CC(O)=O)=CC=3)C(=O)C2=C1 VMSPJYJGWZXQDC-UHFFFAOYSA-N 0.000 claims 1
- WQDWXMNOPFULEC-UHFFFAOYSA-N pyridin-4-ylmethyl 4-benzyl-5-oxo-[1,2,4]triazolo[4,3-a]quinazoline-7-carboxylate Chemical compound C=1C=C(N2C=NN=C2N(CC=2C=CC=CC=2)C2=O)C2=CC=1C(=O)OCC1=CC=NC=C1 WQDWXMNOPFULEC-UHFFFAOYSA-N 0.000 claims 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 84
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 239000000543 intermediate Substances 0.000 description 27
- 239000000203 mixture Substances 0.000 description 25
- ATQUABCIJINPMX-UHFFFAOYSA-N quinazolin-5-ol Chemical compound C1=NC=C2C(O)=CC=CC2=N1 ATQUABCIJINPMX-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 150000002430 hydrocarbons Chemical group 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000003112 inhibitor Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 13
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
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- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
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- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 5
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- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 5
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- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 4
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 4
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
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- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 2
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 2
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- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- YOPJMKIQSXAMSG-UHFFFAOYSA-N 3-benzyl-6-bromo-2-sulfanylidene-1h-quinazolin-4-one Chemical compound O=C1C2=CC(Br)=CC=C2NC(=S)N1CC1=CC=CC=C1 YOPJMKIQSXAMSG-UHFFFAOYSA-N 0.000 description 2
- UMNZIKCNZQBTLB-UHFFFAOYSA-N 4-benzyl-6-bromoimidazo[1,2-a]quinazolin-5-one Chemical compound BrC1=CC=CC(N2C=CN=C22)=C1C(=O)N2CC1=CC=CC=C1 UMNZIKCNZQBTLB-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
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- Neurology (AREA)
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- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US26875701P | 2001-02-14 | 2001-02-14 | |
| US268757P | 2009-06-16 |
Publications (1)
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| ES2239216T3 true ES2239216T3 (es) | 2005-09-16 |
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| EP (1) | EP1362048B1 (enExample) |
| JP (1) | JP2004521908A (enExample) |
| AR (1) | AR032677A1 (enExample) |
| AT (1) | ATE294805T1 (enExample) |
| BR (1) | BR0207270A (enExample) |
| CA (1) | CA2437588A1 (enExample) |
| DE (1) | DE60203995T2 (enExample) |
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| MX (1) | MXPA03007249A (enExample) |
| PA (1) | PA8539501A1 (enExample) |
| PE (1) | PE20020885A1 (enExample) |
| SV (1) | SV2002000875A (enExample) |
| WO (1) | WO2002064595A1 (enExample) |
Families Citing this family (46)
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| WO2002064598A1 (en) * | 2001-02-14 | 2002-08-22 | Warner-Lambert Company Llc | Thieno'2,3-d pyrimidindione derivatives as matrix metalloproteinase inhibitors |
| PA8539501A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Compuestos triazolo como inhibidores de mmp |
| US6924276B2 (en) | 2001-09-10 | 2005-08-02 | Warner-Lambert Company | Diacid-substituted heteroaryl derivatives as matrix metalloproteinase inhibitors |
| MXPA04002537A (es) | 2001-10-12 | 2004-05-31 | Warner Lambert Co | Alquinos como inhibidores de metaloproteinasa de matriz. |
| US6962922B2 (en) | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| US6747147B2 (en) | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6894057B2 (en) | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US20040006077A1 (en) * | 2002-06-25 | 2004-01-08 | Bernard Gaudilliere | Thiazine and oxazine derivatives as MMP-13 inhibitors |
| AU2003281169A1 (en) * | 2002-07-17 | 2004-02-02 | Warner-Lambert Company Llc | Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib |
| JP2006502114A (ja) * | 2002-07-17 | 2006-01-19 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | マトリクスメタロプロテイナーゼ−１３のアロステリックアルキン阻害薬とセレコキシブまたはバルデコキシブとの組合せ |
| EP1531904A1 (en) * | 2002-07-17 | 2005-05-25 | Warner-Lambert Company LLC | Combination of an allosteric inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib |
| MXPA05000729A (es) * | 2002-07-17 | 2005-04-08 | Warner Lambert Co | Combinacion de un inhibidor alosterico de metaloproteinasa-13 de matriz con celecoxib o valdecoxib. |
| AU2003253165A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Pyrimidine fused bicyclic metalloproteinase inhibitors |
| AU2003250482A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Phthalimide derivatives as matrix metalloproteinase inhibitors |
| WO2004014867A2 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Matrix metalloproteinase inhibitors and methods for identification of lead compounds |
| AU2003249539A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Cyclic compounds containing zinc binding groups as matrix metalloproteinase inhibitors |
| WO2004014354A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | 1,6-fused uracil derivatives as matrix metalloproteinase inhibitors |
| AU2003253186A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Fused tetrahydropyridine derivatives as matrix metalloproteinase inhibitors |
| WO2004014378A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | 3-isoquinolinone derivatives as matrix metalloproteinase inhiitors |
| WO2004014868A2 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Pyrimidine-2,4-dione derivatives as matrix metalloproteinase inhibitors |
| AU2003250475A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | 5,6-fused 3,4-dihydropyrimidine-2-one derivatives as matrix metalloproteinase inhibitors |
| WO2004014908A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Heterobicylcic metalloproteinase inhibitors |
| BR0313384A (pt) | 2002-08-13 | 2005-07-12 | Warner Lambert Co | Derivados de cromona como inibidores de metaloproteinases de matriz |
| WO2004014375A2 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Fused bicyclic metalloproteinase inhibitors |
| CA2492019A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Isoquinoline derivatives as matrix metalloproteinase inhibitors |
| BR0313459A (pt) | 2002-08-13 | 2005-06-21 | Warner Lambert Co | Derivados monocìclicos como inibidores de metaloproteinases de matriz |
| WO2004014866A1 (en) | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Azaisoquinoline derivatives as matrix metalloproteinase inhibitors |
| AU2003250470A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Pyrimidinone fused bicyclic metalloproteinase inhibitors |
| PA8578101A1 (es) | 2002-08-13 | 2004-05-07 | Warner Lambert Co | Derivados de heterobiarilo como inhibidores de metaloproteinasa de la matriz |
| US20040142950A1 (en) * | 2003-01-17 | 2004-07-22 | Bunker Amy Mae | Amide and ester matrix metalloproteinase inhibitors |
| WO2005002585A1 (en) * | 2003-07-02 | 2005-01-13 | Warner-Lambert Company Llc | Combination of an allosteric inhibitor of matrix metalloproteinase-13 and a ligand to an alpha-2-delta receptor |
| WO2005016926A1 (en) * | 2003-08-19 | 2005-02-24 | Warner-Lambert Company Llc | Pyrido [3,4-d] pyrimidine derivatives as matrix metalloproteinase-13 inhibitors |
| US20060247231A1 (en) * | 2003-12-18 | 2006-11-02 | Warner-Lambert Company Llc | Amide and ester matrix metalloproteinase inhibitors |
| AU2006251989B2 (en) * | 2005-05-20 | 2010-05-27 | Alantos-Pharmaceuticals, Inc. | Pyrimidine or triazine fused bicyclic metalloprotease inhibitors |
| US20070155738A1 (en) | 2005-05-20 | 2007-07-05 | Alantos Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
| US7795877B2 (en) * | 2006-11-02 | 2010-09-14 | Current Technologies, Llc | Power line communication and power distribution parameter measurement system and method |
| CA2670083A1 (en) * | 2006-11-20 | 2008-05-29 | Alantos Pharmaceuticals Holding, Inc. | Heterobicyclic metalloprotease inhibitors |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| WO2009088990A1 (en) | 2008-01-04 | 2009-07-16 | Intellikine, Inc. | Certain chemical entities, compositions and methods |
| DE102010031945A1 (de) * | 2010-07-22 | 2012-01-26 | Osram Opto Semiconductors Gmbh | Halbleiterbauelement und Verfahren zur Herstellung eines Halbleiterbauelements |
| NZ612909A (en) | 2011-01-10 | 2015-09-25 | Infinity Pharmaceuticals Inc | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| CA2890105C (en) | 2012-11-01 | 2023-03-21 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| WO2017223422A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| CN115197225B (zh) * | 2021-09-03 | 2023-04-11 | 贵州大学 | 一种五元杂环并喹唑啉酮类化合物及其制备方法 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4455311A (en) * | 1981-08-28 | 1984-06-19 | Hoffmann-La Roche Inc. | Imidazoquinazoline derivatives which inhibit the aggregation of blood platelets, inhibit gastric secretion or have activity on the circulatory system |
| IL66835A (en) * | 1981-09-24 | 1988-05-31 | Roussel Uclaf | 1,4-disubstituted(1,2,4)triazolo(4,3-alpha)quinazolin-5(4h)-one derivatives and their salts,their preparation and pharmaceutical compositions containing them |
| DE3677445D1 (de) * | 1985-09-30 | 1991-03-14 | Ciba Geigy Ag | 2-substituierte-e-kondensierte(1,5-c)-pyrimidine, pharmazeutische zubereitungen und ihre verwendung. |
| US6008243A (en) | 1996-10-24 | 1999-12-28 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
| MXPA99001974A (es) | 1996-12-09 | 2002-03-27 | Warner Lambert Co | Metodo para tratar y prevenir fallas cardiacas y dilatacion ventricular. |
| JPH11199512A (ja) | 1997-10-24 | 1999-07-27 | Pfizer Prod Inc | 変形性関節症および他のｍｍｐ媒介疾患の治療のためのｍｍｐ−１３選択的阻害剤の使用 |
| UA59453C2 (uk) | 1998-08-12 | 2003-09-15 | Пфайзер Продактс Інк. | Похідні гідроксипіпеколат гідроксамової кислоти як інгібітори матричних металопротеїназ |
| FR2792938B1 (fr) * | 1999-04-28 | 2001-07-06 | Warner Lambert Co | NOUVELLES 1-AMINO TRIAZOLO [4,3-a] QUINAZOLINE-5-ONES INHIBITRICES DE PHOSPHODIESTERASES IV |
| PA8498701A1 (es) | 1999-08-12 | 2002-08-26 | Pfizer Prod Inc | Pirimidina-2,4,6-trionas inhibidores de metaloproteinasas |
| US6934639B1 (en) | 2000-02-25 | 2005-08-23 | Wyeth | Methods for designing agents that interact with MMP-13 |
| EP1138680A1 (en) | 2000-03-29 | 2001-10-04 | Pfizer Products Inc. | Gem substituted sulfonyl hydroxamic acids as MMP inhibitors |
| KR20040004412A (ko) | 2000-10-26 | 2004-01-13 | 화이자 프로덕츠 인크. | 스피로-피리미딘-2,4,6-트리온 메탈로프로테이나제 억제제 |
| KR20030061825A (ko) | 2000-10-26 | 2003-07-22 | 화이자 프로덕츠 인크. | 피리미딘-2,4,6-트리온 메탈로프로테이나제 억제제 |
| 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 |
| PA8539501A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Compuestos triazolo como inhibidores de mmp |
| MXPA04003008A (es) | 2001-10-12 | 2004-07-16 | Warner Lambert Co | Compuestos pirimidina de anillo fusionado alquinilado como inhibidores de metaloproteasa 13 de la matriz. |
| US6962922B2 (en) * | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| MXPA04002537A (es) | 2001-10-12 | 2004-05-31 | Warner Lambert Co | Alquinos como inhibidores de metaloproteinasa de matriz. |
| US6747147B2 (en) * | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6894057B2 (en) * | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| WO2003076416A1 (en) | 2002-03-08 | 2003-09-18 | Warner-Lambert Company Llc | Oxo azabicyclic compounds |
| AU2002333256A1 (en) | 2002-06-25 | 2004-01-06 | Warner-Lambert Company Llc | Thiazine and oxazine derivatives as mmp-13 inhibitors for treating arthritis |
| US20040006077A1 (en) * | 2002-06-25 | 2004-01-08 | Bernard Gaudilliere | Thiazine and oxazine derivatives as MMP-13 inhibitors |
| AU2003249539A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Cyclic compounds containing zinc binding groups as matrix metalloproteinase inhibitors |
-
2002
- 2002-02-08 PA PA20028539501A patent/PA8539501A1/es unknown
- 2002-02-11 BR BR0207270-0A patent/BR0207270A/pt not_active IP Right Cessation
- 2002-02-11 DE DE60203995T patent/DE60203995T2/de not_active Expired - Fee Related
- 2002-02-11 MX MXPA03007249A patent/MXPA03007249A/es unknown
- 2002-02-11 AT AT02702366T patent/ATE294805T1/de not_active IP Right Cessation
- 2002-02-11 ES ES02702366T patent/ES2239216T3/es not_active Expired - Lifetime
- 2002-02-11 EP EP02702366A patent/EP1362048B1/en not_active Expired - Lifetime
- 2002-02-11 CA CA002437588A patent/CA2437588A1/en not_active Abandoned
- 2002-02-11 JP JP2002564526A patent/JP2004521908A/ja not_active Abandoned
- 2002-02-11 WO PCT/EP2002/001961 patent/WO2002064595A1/en not_active Ceased
- 2002-02-13 HN HN2002000038A patent/HN2002000038A/es unknown
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- 2002-02-13 AR ARP020100471A patent/AR032677A1/es not_active Application Discontinuation
- 2002-02-13 SV SV2002000875A patent/SV2002000875A/es not_active Application Discontinuation
- 2002-02-14 US US10/075,654 patent/US6849637B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002064595A1 (en) | 2002-08-22 |
| DE60203995T2 (de) | 2005-09-22 |
| PE20020885A1 (es) | 2002-10-26 |
| US20020151558A1 (en) | 2002-10-17 |
| JP2004521908A (ja) | 2004-07-22 |
| MXPA03007249A (es) | 2005-02-14 |
| EP1362048A1 (en) | 2003-11-19 |
| AR032677A1 (es) | 2003-11-19 |
| DE60203995D1 (de) | 2005-06-09 |
| CA2437588A1 (en) | 2002-08-22 |
| US6849637B2 (en) | 2005-02-01 |
| PA8539501A1 (es) | 2002-09-30 |
| BR0207270A (pt) | 2004-02-10 |
| ATE294805T1 (de) | 2005-05-15 |
| SV2002000875A (es) | 2002-10-04 |
| EP1362048B1 (en) | 2005-05-04 |
| HN2002000038A (es) | 2002-09-05 |
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