SK75094A3 - Naphthyridine derivatives - Google Patents
Naphthyridine derivatives Download PDFInfo
- Publication number
- SK75094A3 SK75094A3 SK750-94A SK75094A SK75094A3 SK 75094 A3 SK75094 A3 SK 75094A3 SK 75094 A SK75094 A SK 75094A SK 75094 A3 SK75094 A3 SK 75094A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- formula
- alkyl
- carbon atoms
- hydrogen atom
- Prior art date
Links
- 150000005054 naphthyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 188
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 94
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 58
- 239000001257 hydrogen Substances 0.000 claims abstract description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 28
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 9
- 125000003277 amino group Chemical group 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 6
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 4
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims abstract 3
- 125000005019 carboxyalkenyl group Chemical group 0.000 claims abstract 3
- 125000005080 alkoxycarbonylalkenyl group Chemical group 0.000 claims abstract 2
- -1 or C 1 -C 6 alkanoyl Chemical group 0.000 claims description 83
- 125000004432 carbon atom Chemical group C* 0.000 claims description 78
- 125000005843 halogen group Chemical group 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 238000010438 heat treatment Methods 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000002585 base Substances 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 9
- 208000025747 Rheumatic disease Diseases 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- AQZNKLJRHSWVOV-UHFFFAOYSA-N ethyl 6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 AQZNKLJRHSWVOV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 2
- MFQRHPQDMCQXGL-UHFFFAOYSA-N 6-ethoxy-n-(4-methoxyphenyl)-7-methyl-1,8-naphthyridin-4-amine Chemical compound C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 MFQRHPQDMCQXGL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 239000011260 aqueous acid Substances 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
- 125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- UXBIXOXDACBTDG-UHFFFAOYSA-N 1-adamantyl radical Chemical compound C1C(C2)CC3C[C]1CC2C3 UXBIXOXDACBTDG-UHFFFAOYSA-N 0.000 claims 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims 1
- KHVFTTVPXONUEK-UHFFFAOYSA-N 4-[(6-ethoxy-7-methyl-1,8-naphthyridin-4-yl)amino]-2,6-dimethylphenol Chemical compound C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC(C)=C(O)C(C)=C1 KHVFTTVPXONUEK-UHFFFAOYSA-N 0.000 claims 1
- 239000012380 dealkylating agent Substances 0.000 claims 1
- 150000003053 piperidines Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 122
- 239000003435 antirheumatic agent Substances 0.000 abstract description 6
- 125000004414 alkyl thio group Chemical group 0.000 abstract description 2
- 125000001589 carboacyl group Chemical group 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 3
- 125000002723 alicyclic group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 112
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 239000007787 solid Substances 0.000 description 29
- 238000003756 stirring Methods 0.000 description 28
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 239000005662 Paraffin oil Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- AQSRRZGQRFFFGS-UHFFFAOYSA-N 2-methylpyridin-3-ol Chemical compound CC1=NC=CC=C1O AQSRRZGQRFFFGS-UHFFFAOYSA-N 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 230000003628 erosive effect Effects 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- CGXLVFZJJOXEDF-UHFFFAOYSA-N 1,8-naphthyridine-3-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CN=C21 CGXLVFZJJOXEDF-UHFFFAOYSA-N 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 201000008482 osteoarthritis Diseases 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- BATUATIMONERQY-UHFFFAOYSA-N 5-ethoxy-6-methylpyridin-2-amine Chemical compound CCOC1=CC=C(N)N=C1C BATUATIMONERQY-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
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 235000019271 petrolatum Nutrition 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 3
- ADHVKJKRZSDQSU-UHFFFAOYSA-N 5-chloro-3-ethoxy-2-methyl-1,8-naphthyridine Chemical compound C1=CN=C2N=C(C)C(OCC)=CC2=C1Cl ADHVKJKRZSDQSU-UHFFFAOYSA-N 0.000 description 3
- YLWLDKVTAXTNDI-UHFFFAOYSA-N 6-ethoxy-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound C1=CN=C2N=C(C)C(OCC)=CC2=C1O YLWLDKVTAXTNDI-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- NSNHWTBQMQIDCF-UHFFFAOYSA-N dihydrate;hydrochloride Chemical compound O.O.Cl NSNHWTBQMQIDCF-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000002702 enteric coating Substances 0.000 description 3
- 238000009505 enteric coating Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 201000004595 synovitis Diseases 0.000 description 3
- GHBCHRXBACFGBU-UHFFFAOYSA-N 1-[6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridin-3-yl]butan-1-ol Chemical compound CCCC(O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 GHBCHRXBACFGBU-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 2
- 125000000872 2-diethylaminoethoxy group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 2
- QCGBSQNGOSTBFH-UHFFFAOYSA-N 3-[3-ethoxy-6-ethoxycarbonyl-5-(4-methoxyanilino)-1,8-naphthyridin-2-yl]prop-2-enoic acid Chemical compound CCOC(=O)C1=CN=C2N=C(C=CC(O)=O)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 QCGBSQNGOSTBFH-UHFFFAOYSA-N 0.000 description 2
- YUHXVWQQUNUOGH-UHFFFAOYSA-N 3-ethoxy-2-methylpyridine Chemical compound CCOC1=CC=CN=C1C YUHXVWQQUNUOGH-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- NFYYDQMFURPHCC-UHFFFAOYSA-N 6-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=CC=CC(C(F)(F)F)=N1 NFYYDQMFURPHCC-UHFFFAOYSA-N 0.000 description 2
- YCBVVXQXUTVSDX-UHFFFAOYSA-N 6-bromo-n-(4-methoxyphenyl)-7-methyl-1,8-naphthyridin-4-amine Chemical compound C1=CC(OC)=CC=C1NC1=CC=NC2=NC(C)=C(Br)C=C12 YCBVVXQXUTVSDX-UHFFFAOYSA-N 0.000 description 2
- KGLPWQYXOHFIAB-UHFFFAOYSA-N 6-ethoxy-2,7-dimethyl-1h-1,8-naphthyridin-4-one Chemical compound C1=C(C)N=C2N=C(C)C(OCC)=CC2=C1O KGLPWQYXOHFIAB-UHFFFAOYSA-N 0.000 description 2
- MYIVFWFDKVRXMV-UHFFFAOYSA-N 6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxamide Chemical compound NC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 MYIVFWFDKVRXMV-UHFFFAOYSA-N 0.000 description 2
- PEHFDOOJHVFPRV-UHFFFAOYSA-N 6-ethoxy-n-(4-methoxyphenyl)-3,7-dimethyl-1,8-naphthyridin-4-amine Chemical compound CC1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 PEHFDOOJHVFPRV-UHFFFAOYSA-N 0.000 description 2
- HSVAGTSDJPAWEZ-UHFFFAOYSA-N 6-ethoxy-n-(4-methoxyphenyl)-7-methyl-1,8-naphthyridin-4-amine;hydrochloride Chemical compound Cl.C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 HSVAGTSDJPAWEZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- RIPWOVALKNKSAG-UHFFFAOYSA-N [6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridin-3-yl]methanol Chemical compound OCC1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 RIPWOVALKNKSAG-UHFFFAOYSA-N 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003356 anti-rheumatic effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- PQMDBJDHPGZDDT-UHFFFAOYSA-N ethyl 4-(4-methoxyanilino)-7-(trifluoromethyl)-1,8-naphthyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2N=C(C(F)(F)F)C=CC2=C1NC1=CC=C(OC)C=C1 PQMDBJDHPGZDDT-UHFFFAOYSA-N 0.000 description 2
- QKZONHJYUBHLPC-UHFFFAOYSA-N ethyl 4-(4-methoxyanilino)-7-oxo-8h-1,8-naphthyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2NC(=O)C=CC2=C1NC1=CC=C(OC)C=C1 QKZONHJYUBHLPC-UHFFFAOYSA-N 0.000 description 2
- JJCODSWKMAHWBP-UHFFFAOYSA-N ethyl 4-chloro-6-ethoxy-7-methyl-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(C)C(OCC)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 JJCODSWKMAHWBP-UHFFFAOYSA-N 0.000 description 2
- XSTNPHZJFLKSKX-UHFFFAOYSA-N ethyl 6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 XSTNPHZJFLKSKX-UHFFFAOYSA-N 0.000 description 2
- UCYSCIJWSTXBHG-UHFFFAOYSA-N ethyl 6-ethoxy-7-methyl-4-oxo-1h-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(C)C(OCC)=CC2=C(O)C(C(=O)OCC)=CN=C21 UCYSCIJWSTXBHG-UHFFFAOYSA-N 0.000 description 2
- GNCGFJDCHSKSFZ-UHFFFAOYSA-N ethyl 7-ethoxy-4-(4-methoxyanilino)-1,8-naphthyridine-3-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=C2N=C(OCC)C=CC2=C1NC1=CC=C(OC)C=C1 GNCGFJDCHSKSFZ-UHFFFAOYSA-N 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229960002390 flurbiprofen Drugs 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- QHDNINLNSHGWBR-UHFFFAOYSA-N methyl 5-(4-methoxyanilino)-1,8-naphthyridine-2-carboxylate Chemical compound C=1C=NC2=NC(C(=O)OC)=CC=C2C=1NC1=CC=C(OC)C=C1 QHDNINLNSHGWBR-UHFFFAOYSA-N 0.000 description 2
- 108010077055 methylated bovine serum albumin Proteins 0.000 description 2
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- IOELKYCBKDKOAA-UHFFFAOYSA-N 1-(4-chloro-6-ethoxy-7-methyl-2h-1,8-naphthyridin-1-yl)butan-1-one Chemical compound CCOC1=C(C)N=C2N(C(=O)CCC)CC=C(Cl)C2=C1 IOELKYCBKDKOAA-UHFFFAOYSA-N 0.000 description 1
- MKPLMZYDVOYENW-UHFFFAOYSA-N 1-[6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridin-3-yl]butan-1-one Chemical compound CCCC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 MKPLMZYDVOYENW-UHFFFAOYSA-N 0.000 description 1
- PQGJNXVQJFTFHE-UHFFFAOYSA-N 1-[6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridin-3-yl]butan-1-one;hydrochloride Chemical compound Cl.CCCC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 PQGJNXVQJFTFHE-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- NQUIRWXTTAMWIU-UHFFFAOYSA-N 1h-1,8-naphthyridin-4-one Chemical compound C1=CC=C2C(O)=CC=NC2=N1 NQUIRWXTTAMWIU-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- FNORUNUDZNWQFF-UHFFFAOYSA-N 2,6-dimethyl-4-nitrophenol Chemical compound CC1=CC([N+]([O-])=O)=CC(C)=C1O FNORUNUDZNWQFF-UHFFFAOYSA-N 0.000 description 1
- SRCAKTIYISIAIT-UHFFFAOYSA-N 2-(4-aminophenoxy)ethanol Chemical compound NC1=CC=C(OCCO)C=C1 SRCAKTIYISIAIT-UHFFFAOYSA-N 0.000 description 1
- YAPAEYFBLRVUMH-UHFFFAOYSA-N 2-(4-nitrophenoxy)ethanol Chemical compound OCCOC1=CC=C([N+]([O-])=O)C=C1 YAPAEYFBLRVUMH-UHFFFAOYSA-N 0.000 description 1
- ADVQMCQMDHBTHJ-UHFFFAOYSA-N 2-chloro-6-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC(Cl)=N1 ADVQMCQMDHBTHJ-UHFFFAOYSA-N 0.000 description 1
- IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 1
- ZNKSTHRFGWKDQK-UHFFFAOYSA-N 2-methyl-3-propoxypyridine Chemical compound CCCOC1=CC=CN=C1C ZNKSTHRFGWKDQK-UHFFFAOYSA-N 0.000 description 1
- SYEGYWCLXLAFQV-UHFFFAOYSA-N 2-methyl-6-nitro-3-propoxypyridine Chemical compound CCCOC1=CC=C([N+]([O-])=O)N=C1C SYEGYWCLXLAFQV-UHFFFAOYSA-N 0.000 description 1
- HMRIWBBWYXEHRZ-UHFFFAOYSA-N 2-propoxypyridine Chemical compound CCCOC1=CC=CC=N1 HMRIWBBWYXEHRZ-UHFFFAOYSA-N 0.000 description 1
- UHEXNIICCCHZNI-UHFFFAOYSA-N 3-(3-ethoxy-6-ethoxycarbonyl-5-oxo-8h-1,8-naphthyridin-2-yl)prop-2-enoic acid Chemical compound N1=C(C=CC(O)=O)C(OCC)=CC2=C(O)C(C(=O)OCC)=CN=C21 UHEXNIICCCHZNI-UHFFFAOYSA-N 0.000 description 1
- UVXFYVIGAUPIOP-UHFFFAOYSA-N 3-(4-aminophenoxy)propane-1,2-diol Chemical compound NC1=CC=C(OCC(O)CO)C=C1 UVXFYVIGAUPIOP-UHFFFAOYSA-N 0.000 description 1
- YERGZLQRVWFVAZ-UHFFFAOYSA-N 3-(4-nitrophenoxy)propane-1,2-diol Chemical compound OCC(O)COC1=CC=C([N+]([O-])=O)C=C1 YERGZLQRVWFVAZ-UHFFFAOYSA-N 0.000 description 1
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 1
- KSDIXRXFSGLELT-UHFFFAOYSA-N 3-[3-ethoxy-5-(4-methoxyanilino)-1,8-naphthyridin-2-yl]prop-2-enoic acid Chemical compound C1=CN=C2N=C(C=CC(O)=O)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 KSDIXRXFSGLELT-UHFFFAOYSA-N 0.000 description 1
- RRZIKQCSJLKJFF-UHFFFAOYSA-N 3-[4-[(6-ethoxy-7-methyl-1,8-naphthyridin-4-yl)amino]phenoxy]propane-1,2-diol Chemical compound C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OCC(O)CO)C=C1 RRZIKQCSJLKJFF-UHFFFAOYSA-N 0.000 description 1
- ZVKPFYIXILTAKN-UHFFFAOYSA-N 3-[4-[(6-ethoxy-7-methyl-1,8-naphthyridin-4-yl)amino]phenoxy]propane-1,2-diol;hydrochloride Chemical compound Cl.C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OCC(O)CO)C=C1 ZVKPFYIXILTAKN-UHFFFAOYSA-N 0.000 description 1
- BJEZWGZDQXAODC-UHFFFAOYSA-N 3-bromo-6-ethoxy-n-(4-methoxyphenyl)-7-methyl-1,8-naphthyridin-4-amine Chemical compound BrC1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 BJEZWGZDQXAODC-UHFFFAOYSA-N 0.000 description 1
- YLHVVHUHAOIYOX-UHFFFAOYSA-N 3-butanoyl-6-ethoxy-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N1=C(C)C(OCC)=CC2=C(O)C(C(=O)CCC)=CN=C21 YLHVVHUHAOIYOX-UHFFFAOYSA-N 0.000 description 1
- OBDWATZMYGTZDJ-UHFFFAOYSA-N 3-ethoxy-2-methyl-6-nitropyridine Chemical compound CCOC1=CC=C([N+]([O-])=O)N=C1C OBDWATZMYGTZDJ-UHFFFAOYSA-N 0.000 description 1
- ZBGFOTQTSACWJZ-UHFFFAOYSA-N 3-ethoxy-6-ethoxycarbonyl-5-oxo-8h-1,8-naphthyridine-2-carboxylic acid Chemical compound N1=C(C(O)=O)C(OCC)=CC2=C(O)C(C(=O)OCC)=CN=C21 ZBGFOTQTSACWJZ-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- UOKVFMZISSJYNM-UHFFFAOYSA-N 3-methoxy-2-methyl-6-nitropyridine Chemical compound COC1=CC=C([N+]([O-])=O)N=C1C UOKVFMZISSJYNM-UHFFFAOYSA-N 0.000 description 1
- QRCUQLANPHYVEH-UHFFFAOYSA-N 3-methoxy-2-methylpyridine Chemical compound COC1=CC=CN=C1C QRCUQLANPHYVEH-UHFFFAOYSA-N 0.000 description 1
- HHAMGUKELAASPP-UHFFFAOYSA-N 4-(1-adamantyloxy)aniline Chemical compound C1=CC(N)=CC=C1OC1(C2)CC(C3)CC2CC3C1 HHAMGUKELAASPP-UHFFFAOYSA-N 0.000 description 1
- CZGCEKJOLUNIFY-UHFFFAOYSA-N 4-Chloronitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1 CZGCEKJOLUNIFY-UHFFFAOYSA-N 0.000 description 1
- FOWDPOYJLFUTEX-UHFFFAOYSA-N 4-[(6-ethoxy-7-methyl-1,8-naphthyridin-4-yl)amino]-2,6-dimethylphenol;hydrochloride Chemical compound Cl.C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC(C)=C(O)C(C)=C1 FOWDPOYJLFUTEX-UHFFFAOYSA-N 0.000 description 1
- OHRWPLKTKATNCT-UHFFFAOYSA-N 4-[(6-ethoxy-7-methyl-1,8-naphthyridin-4-yl)amino]phenol Chemical compound C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(O)C=C1 OHRWPLKTKATNCT-UHFFFAOYSA-N 0.000 description 1
- OMVFXCQLSCPJNR-UHFFFAOYSA-N 4-amino-2,6-dimethylphenol Chemical compound CC1=CC(N)=CC(C)=C1O OMVFXCQLSCPJNR-UHFFFAOYSA-N 0.000 description 1
- PIVHIKGMNVGPKN-UHFFFAOYSA-N 4-chloro-6-ethoxy-7-methyl-1,8-naphthyridine-3-carboxamide Chemical compound NC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1Cl PIVHIKGMNVGPKN-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- JFXDIXYFXDOZIT-UHFFFAOYSA-N 4-methoxy-n-methylaniline Chemical compound CNC1=CC=C(OC)C=C1 JFXDIXYFXDOZIT-UHFFFAOYSA-N 0.000 description 1
- WOYZXEVUWXQVNV-UHFFFAOYSA-N 4-phenoxyaniline Chemical compound C1=CC(N)=CC=C1OC1=CC=CC=C1 WOYZXEVUWXQVNV-UHFFFAOYSA-N 0.000 description 1
- SEOZHXRTVJPQPZ-UHFFFAOYSA-N 5-bromo-6-methylpyridin-2-amine Chemical compound CC1=NC(N)=CC=C1Br SEOZHXRTVJPQPZ-UHFFFAOYSA-N 0.000 description 1
- YONSQTZAGQQNHL-UHFFFAOYSA-N 5-chloro-3-ethoxy-2,6-dimethyl-1,8-naphthyridine Chemical compound CC1=CN=C2N=C(C)C(OCC)=CC2=C1Cl YONSQTZAGQQNHL-UHFFFAOYSA-N 0.000 description 1
- URVQJNZNQGOKPD-UHFFFAOYSA-N 5-chloro-3-ethoxy-2,7-dimethyl-1,8-naphthyridine Chemical compound C1=C(C)N=C2N=C(C)C(OCC)=CC2=C1Cl URVQJNZNQGOKPD-UHFFFAOYSA-N 0.000 description 1
- WYHJSBYUEPREHU-UHFFFAOYSA-N 5-methoxy-6-methylpyridin-2-amine Chemical compound COC1=CC=C(N)N=C1C WYHJSBYUEPREHU-UHFFFAOYSA-N 0.000 description 1
- BXPFRZBLRNEWCV-UHFFFAOYSA-N 6-bromo-5-chloro-3-ethoxy-2-methyl-1,8-naphthyridine Chemical compound BrC1=CN=C2N=C(C)C(OCC)=CC2=C1Cl BXPFRZBLRNEWCV-UHFFFAOYSA-N 0.000 description 1
- GMWZPVNIMVUDTO-UHFFFAOYSA-N 6-bromo-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound C1=CC(O)=C2C=C(Br)C(C)=NC2=N1 GMWZPVNIMVUDTO-UHFFFAOYSA-N 0.000 description 1
- WSSWHISIPHSDPR-UHFFFAOYSA-N 6-ethoxy-3,7-dimethyl-1h-1,8-naphthyridin-4-one Chemical compound CC1=CN=C2N=C(C)C(OCC)=CC2=C1O WSSWHISIPHSDPR-UHFFFAOYSA-N 0.000 description 1
- MEQTVTFDSGTYGO-UHFFFAOYSA-N 6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 MEQTVTFDSGTYGO-UHFFFAOYSA-N 0.000 description 1
- OIFDMJDJYHFNSH-UHFFFAOYSA-N 6-ethoxy-7-methyl-1,8-naphthyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1 OIFDMJDJYHFNSH-UHFFFAOYSA-N 0.000 description 1
- FJYGNZFBNMBOJO-UHFFFAOYSA-N 6-ethoxy-7-methyl-4-(3,4,5-trimethoxyanilino)-1,8-naphthyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC(OC)=C(OC)C(OC)=C1 FJYGNZFBNMBOJO-UHFFFAOYSA-N 0.000 description 1
- LUNSDBKCXNMDFR-UHFFFAOYSA-N 6-ethoxy-7-methyl-4-oxo-1h-1,8-naphthyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1O LUNSDBKCXNMDFR-UHFFFAOYSA-N 0.000 description 1
- CUCAZUVWRXRMMA-UHFFFAOYSA-N 6-ethoxy-7-methyl-n-(4-phenoxyphenyl)-1,8-naphthyridin-4-amine Chemical compound C1=CN=C2N=C(C)C(OCC)=CC2=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 CUCAZUVWRXRMMA-UHFFFAOYSA-N 0.000 description 1
- NAASENSVISQXTO-UHFFFAOYSA-N 6-ethoxy-n-(4-methoxyphenyl)-2,7-dimethyl-1,8-naphthyridin-4-amine;hydrochloride Chemical compound Cl.C1=C(C)N=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OC)C=C1 NAASENSVISQXTO-UHFFFAOYSA-N 0.000 description 1
- VRZIITVWIJSXOA-UHFFFAOYSA-N 6-ethoxypyridin-2-amine Chemical compound CCOC1=CC=CC(N)=N1 VRZIITVWIJSXOA-UHFFFAOYSA-N 0.000 description 1
- ZOJZGGBQJNUBBJ-UHFFFAOYSA-N 6-hydroxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1NC1=C(C(O)=O)C=NC2=NC(C)=C(O)C=C12 ZOJZGGBQJNUBBJ-UHFFFAOYSA-N 0.000 description 1
- WTSGKMWFXDLBNZ-UHFFFAOYSA-N 6-methyl-5-propoxypyridin-2-amine Chemical compound CCCOC1=CC=C(N)N=C1C WTSGKMWFXDLBNZ-UHFFFAOYSA-N 0.000 description 1
- QUXLCYFNVNNRBE-UHFFFAOYSA-N 6-methylpyridin-2-amine Chemical compound CC1=CC=CC(N)=N1 QUXLCYFNVNNRBE-UHFFFAOYSA-N 0.000 description 1
- PYCCQLPUMLIPQU-UHFFFAOYSA-N 7-ethoxy-2,6-dimethylpyrido[1,2-a]pyrimidin-4-one Chemical compound CC1=CC(=O)N2C(C)=C(OCC)C=CC2=N1 PYCCQLPUMLIPQU-UHFFFAOYSA-N 0.000 description 1
- JVJJTRYGAHJGAZ-UHFFFAOYSA-N 7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N1C=CC(=O)C=2C1=NC(C)=CC=2 JVJJTRYGAHJGAZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- JSVTWWMMZGLSGC-UHFFFAOYSA-N CCCOC1=C(N=C2C(=C1)C(=O)C(=CN2)C(=O)O)C Chemical compound CCCOC1=C(N=C2C(=C1)C(=O)C(=CN2)C(=O)O)C JSVTWWMMZGLSGC-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 101100495769 Caenorhabditis elegans che-1 gene Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 1
- 229940123907 Disease modifying antirheumatic drug Drugs 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- LJWUOFQCMFLSFZ-UHFFFAOYSA-N O.O.Cl.ClC1=C(C(=CC(=C1)NC1=CC=NC2=NC(=C(C=C12)OCC)C)Cl)O.Cl.Cl.ClC1=C(C(=CC(=C1)NC1=CC=NC2=NC(=C(C=C12)OCC)C)Cl)O.O.O Chemical compound O.O.Cl.ClC1=C(C(=CC(=C1)NC1=CC=NC2=NC(=C(C=C12)OCC)C)Cl)O.Cl.Cl.ClC1=C(C(=CC(=C1)NC1=CC=NC2=NC(=C(C=C12)OCC)C)Cl)O.O.O LJWUOFQCMFLSFZ-UHFFFAOYSA-N 0.000 description 1
- 208000025157 Oral disease Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 241001536563 Panus Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- NAZOBHPZYCUDER-UHFFFAOYSA-N [5-(4-methoxyanilino)-1,8-naphthyridin-2-yl]methanol Chemical compound C1=CC(OC)=CC=C1NC1=CC=NC2=NC(CO)=CC=C12 NAZOBHPZYCUDER-UHFFFAOYSA-N 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 208000037329 crystal arthropathy Diseases 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000011928 denatured alcohol Substances 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 1
- LHUZAYREVYDAGJ-UHFFFAOYSA-N dichloromethane;ethyl acetate;methanol Chemical compound OC.ClCCl.CCOC(C)=O LHUZAYREVYDAGJ-UHFFFAOYSA-N 0.000 description 1
- NFSWCQZFLRFYLJ-UHFFFAOYSA-N diethyl 2-[[(6-ethoxypyridin-2-yl)amino]methylidene]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CNC1=CC=CC(OCC)=N1 NFSWCQZFLRFYLJ-UHFFFAOYSA-N 0.000 description 1
- XXUGXDAGLPHHLG-UHFFFAOYSA-N diethyl 2-[[[6-(trifluoromethyl)pyridin-2-yl]amino]methylidene]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CNC1=CC=CC(C(F)(F)F)=N1 XXUGXDAGLPHHLG-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical class O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002745 epiphysis Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- SNASURYOEVANGE-UHFFFAOYSA-N ethyl 2-[[(5-ethoxy-6-methylpyridin-2-yl)amino]methylidene]-3-oxohexanoate Chemical compound CCCC(=O)C(C(=O)OCC)=CNC1=CC=C(OCC)C(C)=N1 SNASURYOEVANGE-UHFFFAOYSA-N 0.000 description 1
- VVCYNVCCODBCOE-UHFFFAOYSA-N ethyl 2-methyl-3-oxopropanoate Chemical compound CCOC(=O)C(C)C=O VVCYNVCCODBCOE-UHFFFAOYSA-N 0.000 description 1
- VAPKBTQVHMPCQP-UHFFFAOYSA-N ethyl 4-(4-methoxyanilino)-7-methyl-6-propoxy-1,8-naphthyridine-3-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=C2N=C(C)C(OCCC)=CC2=C1NC1=CC=C(OC)C=C1 VAPKBTQVHMPCQP-UHFFFAOYSA-N 0.000 description 1
- RLEWHHBVOBDKRF-UHFFFAOYSA-N ethyl 4-anilino-7-methyl-1,8-naphthyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2N=C(C)C=CC2=C1NC1=CC=CC=C1 RLEWHHBVOBDKRF-UHFFFAOYSA-N 0.000 description 1
- DRCVGBLQNNFBQJ-UHFFFAOYSA-N ethyl 4-chloro-6-ethoxy-1,8-naphthyridine-3-carboxylate Chemical compound N1=CC(OCC)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 DRCVGBLQNNFBQJ-UHFFFAOYSA-N 0.000 description 1
- CJDUUOJXQPYBRE-UHFFFAOYSA-N ethyl 4-chloro-6-methoxy-7-methyl-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(C)C(OC)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 CJDUUOJXQPYBRE-UHFFFAOYSA-N 0.000 description 1
- VULMHERCGQCVAJ-UHFFFAOYSA-N ethyl 4-chloro-7-(trifluoromethyl)-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(C(F)(F)F)C=CC2=C(Cl)C(C(=O)OCC)=CN=C21 VULMHERCGQCVAJ-UHFFFAOYSA-N 0.000 description 1
- LGZCKWHHZMMTML-UHFFFAOYSA-N ethyl 4-chloro-7-ethoxy-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(OCC)C=CC2=C(Cl)C(C(=O)OCC)=CN=C21 LGZCKWHHZMMTML-UHFFFAOYSA-N 0.000 description 1
- QOLGEWOROXUOCJ-UHFFFAOYSA-N ethyl 6-bromo-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=C2N=C(C)C(Br)=CC2=C1NC1=CC=C(OC)C=C1 QOLGEWOROXUOCJ-UHFFFAOYSA-N 0.000 description 1
- BYJPEJVHMINDCK-UHFFFAOYSA-N ethyl 6-bromo-4-chloro-7-methyl-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(C)C(Br)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 BYJPEJVHMINDCK-UHFFFAOYSA-N 0.000 description 1
- XVFXCTUUVPBXOL-UHFFFAOYSA-N ethyl 6-bromo-7-methyl-4-oxo-1h-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(C)C(Br)=CC2=C(O)C(C(=O)OCC)=CN=C21 XVFXCTUUVPBXOL-UHFFFAOYSA-N 0.000 description 1
- PPGJGDZYYVXCGQ-UHFFFAOYSA-N ethyl 6-ethoxy-4-(4-ethoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC1=CC=C(OCC)C=C1 PPGJGDZYYVXCGQ-UHFFFAOYSA-N 0.000 description 1
- ISTZKEUFSSBBRU-UHFFFAOYSA-N ethyl 6-ethoxy-4-(4-methoxyanilino)-1,8-naphthyridine-3-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=C2N=CC(OCC)=CC2=C1NC1=CC=C(OC)C=C1 ISTZKEUFSSBBRU-UHFFFAOYSA-N 0.000 description 1
- USEBZWVSTCHLLX-UHFFFAOYSA-N ethyl 6-ethoxy-7-methyl-4-(4-phenoxyanilino)-1,8-naphthyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 USEBZWVSTCHLLX-UHFFFAOYSA-N 0.000 description 1
- VDGUHBCQBLJKMJ-UHFFFAOYSA-N ethyl 6-ethoxy-7-methyl-4-(4-phenoxyanilino)-1,8-naphthyridine-3-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=C2N=C(C)C(OCC)=CC2=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 VDGUHBCQBLJKMJ-UHFFFAOYSA-N 0.000 description 1
- APFIDGWAWPSMNH-UHFFFAOYSA-N ethyl 6-methoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2N=C(C)C(OC)=CC2=C1NC1=CC=C(OC)C=C1 APFIDGWAWPSMNH-UHFFFAOYSA-N 0.000 description 1
- WZPNONPIONPMHG-UHFFFAOYSA-N ethyl 7-ethoxy-4-oxo-1h-1,8-naphthyridine-3-carboxylate Chemical compound N1=C(OCC)C=CC2=C(O)C(C(=O)OCC)=CN=C21 WZPNONPIONPMHG-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 229960004279 formaldehyde Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002344 gold compounds Chemical class 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- ZXRCAYWYTOIRQS-UHFFFAOYSA-N hydron;phenol;chloride Chemical compound Cl.OC1=CC=CC=C1 ZXRCAYWYTOIRQS-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- YEVGPCAJXICMQD-UHFFFAOYSA-N methyl 5-chloro-1,8-naphthyridine-2-carboxylate Chemical compound ClC1=CC=NC2=NC(C(=O)OC)=CC=C21 YEVGPCAJXICMQD-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- ZLZZAXUKBHFTHA-UHFFFAOYSA-N n,n-diethyl-2-(4-nitrophenoxy)ethanamine Chemical compound CCN(CC)CCOC1=CC=C([N+]([O-])=O)C=C1 ZLZZAXUKBHFTHA-UHFFFAOYSA-N 0.000 description 1
- FSRDUCSLELWORM-UHFFFAOYSA-N n-[4-(1-adamantyloxy)phenyl]-6-ethoxy-7-methyl-1,8-naphthyridin-4-amine;hydrochloride Chemical compound Cl.C1C(C2)CC(C3)CC2CC13OC(C=C1)=CC=C1NC1=C2C=C(OCC)C(C)=NC2=NC=C1 FSRDUCSLELWORM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000007944 soluble tablet Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- MQAYPFVXSPHGJM-UHFFFAOYSA-M trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=CC=CC=C1 MQAYPFVXSPHGJM-UHFFFAOYSA-M 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919127252A GB9127252D0 (en) | 1991-12-23 | 1991-12-23 | Therapeutic agents |
| PCT/EP1992/002901 WO1993013097A1 (en) | 1991-12-23 | 1992-12-12 | Anti-rheumatic naphthyridine derivatives |
| CN93109454A CN1096784A (zh) | 1991-12-23 | 1993-06-22 | 含取代4(5)-氨基-1,8-二氨杂萘的治疗剂 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK75094A3 true SK75094A3 (en) | 1995-04-12 |
Family
ID=36822317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK750-94A SK75094A3 (en) | 1991-12-23 | 1992-12-12 | Naphthyridine derivatives |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US5464781A (enExample) |
| EP (1) | EP0618916B1 (enExample) |
| JP (1) | JP2527917B2 (enExample) |
| CN (1) | CN1096784A (enExample) |
| AT (1) | ATE171452T1 (enExample) |
| AU (1) | AU656832B2 (enExample) |
| BG (1) | BG98813A (enExample) |
| CA (1) | CA2125858A1 (enExample) |
| CZ (1) | CZ153594A3 (enExample) |
| DE (1) | DE69227125T2 (enExample) |
| FI (1) | FI943019A0 (enExample) |
| GB (1) | GB9127252D0 (enExample) |
| HR (1) | HRP921455A2 (enExample) |
| HU (1) | HUT66971A (enExample) |
| IL (1) | IL104169A0 (enExample) |
| IN (1) | IN174405B (enExample) |
| MX (1) | MX9207494A (enExample) |
| NO (1) | NO942376L (enExample) |
| NZ (1) | NZ246156A (enExample) |
| SI (1) | SI9200408A (enExample) |
| SK (1) | SK75094A3 (enExample) |
| WO (1) | WO1993013097A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9312891D0 (en) * | 1993-06-22 | 1993-08-04 | Boots Co Plc | Therapeutic agents |
| GB9318931D0 (en) * | 1993-09-14 | 1993-10-27 | Boots Co Plc | Therapeutic agents |
| GB9420168D0 (en) * | 1994-10-06 | 1994-11-23 | Boots Co Plc | Therapeutic agents |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| AU733551B2 (en) * | 1996-09-25 | 2001-05-17 | Astrazeneca Ab | Qinoline derivatives inhibiting the effect of growth factors such as VEGF |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| US6166069A (en) * | 1998-05-12 | 2000-12-26 | American Home Products Corporation | Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia |
| US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| EP1192151B1 (en) | 1999-07-09 | 2007-11-07 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| US7160889B2 (en) | 2000-04-07 | 2007-01-09 | Astrazeneca Ab | Quinazoline compounds |
| US6534656B2 (en) * | 2001-05-31 | 2003-03-18 | North Carolina State University | Short synthesis of pyridine-based pharmaceutical intermediates |
| JP2003329989A (ja) * | 2002-03-06 | 2003-11-19 | Nippon Telegr & Teleph Corp <Ntt> | 光送信装置 |
| GB0230018D0 (en) | 2002-12-23 | 2003-01-29 | Syngenta Ltd | Fungicides |
| WO2005003100A2 (en) | 2003-07-03 | 2005-01-13 | Myriad Genetics, Inc. | 4-arylamino-quinazolines as activators of caspases and inducers of apoptosis |
| WO2006074147A2 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics, Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| US8309562B2 (en) * | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| JP4503022B2 (ja) | 2003-12-23 | 2010-07-14 | ファイザー・インク | 新規キノリン誘導体 |
| US8258145B2 (en) * | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| US7915411B2 (en) * | 2005-12-21 | 2011-03-29 | Abbott Laboratories | Anti-viral compounds |
| US7910595B2 (en) * | 2005-12-21 | 2011-03-22 | Abbott Laboratories | Anti-viral compounds |
| TWI392676B (zh) * | 2005-12-21 | 2013-04-11 | Abbott Lab | 抗病毒化合物、其製備方法及用途 |
| EP2345652A1 (en) | 2005-12-21 | 2011-07-20 | Abbott Laboratories | Antiviral compounds |
| CN102702194A (zh) * | 2005-12-21 | 2012-10-03 | 雅培制药有限公司 | 抗病毒化合物 |
| US8236950B2 (en) | 2006-12-20 | 2012-08-07 | Abbott Laboratories | Anti-viral compounds |
| CA2727103A1 (en) * | 2008-07-03 | 2010-01-07 | Merck Patent Gmbh | Naphthyridinones as aurora kinase inhibitors |
| EP2401275B1 (en) | 2009-02-24 | 2013-07-24 | Respiratorius AB | Naphthyridine derivatives having bronchodilating activity |
| WO2011063398A1 (en) * | 2009-11-23 | 2011-05-26 | Cylene Pharamaceuticals, Inc. | Polymorphs and salts of a kinase inhibitor |
| NZ603332A (en) | 2010-04-02 | 2014-11-28 | Senomyx Inc | Sweet flavor modifier |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4466965A (en) * | 1982-07-26 | 1984-08-21 | American Hospital Supply Corporation | Phthalazine compounds, compositions and use |
| NO174506B (no) * | 1984-10-30 | 1994-02-07 | Usv Pharma Corp | Analogifremgangsmaate ved fremstilling av terapeutisk aktive forbindelser |
| EP0222839A4 (en) * | 1985-05-17 | 1988-11-09 | Univ Australian | ANTI-MALARIA COMPOUNDS. |
| JPS6368568A (ja) * | 1986-09-10 | 1988-03-28 | Otsuka Pharmaceut Factory Inc | ｐ−アミノフエノ−ル誘導体 |
| DE3644825A1 (de) * | 1986-12-31 | 1988-07-14 | Basf Ag | Substituierte 1,8-naphthyridin-derivate und diese enthaltende fungizide |
| JPH07116187B2 (ja) * | 1987-07-22 | 1995-12-13 | シェリング・コーポレーション | 二環式化合物、それらを薬剤として使用すること、それらの製法、およびそれらの製造に有用な中間体 |
| GB8804443D0 (en) * | 1988-02-25 | 1988-03-23 | Smithkline Beckman Intercredit | Compounds |
| US4978661A (en) * | 1988-09-29 | 1990-12-18 | Innocenzo Caruso | Use of 6-halo-4-quinolone compounds and pharmaceutical compositions thereof for the preparation of a medicament for the therapeutical application in rheumatoid arthritis |
| GR900100380A (el) * | 1989-05-20 | 1991-10-10 | Fisons Plc | Μέ?οδος παρασκευής αντι-φλεγμονωδών παραγώγων αμινοφενόλης. |
| AU634561B2 (en) * | 1989-07-27 | 1993-02-25 | Eli Lilly And Company | Naphthyridine derivatives |
| JP2988739B2 (ja) * | 1990-04-16 | 1999-12-13 | 協和醗酵工業株式会社 | １，８−ナフチリジン−２−オン誘導体 |
| JP3157077B2 (ja) * | 1994-02-16 | 2001-04-16 | 内山工業株式会社 | ベアリングシール |
-
1991
- 1991-12-23 GB GB919127252A patent/GB9127252D0/en active Pending
-
1992
- 1992-10-12 US US08/244,369 patent/US5464781A/en not_active Expired - Lifetime
- 1992-12-12 JP JP5511397A patent/JP2527917B2/ja not_active Expired - Fee Related
- 1992-12-12 EP EP93900052A patent/EP0618916B1/en not_active Expired - Lifetime
- 1992-12-12 DE DE69227125T patent/DE69227125T2/de not_active Expired - Fee Related
- 1992-12-12 AU AU31587/93A patent/AU656832B2/en not_active Ceased
- 1992-12-12 CZ CZ941535A patent/CZ153594A3/cs unknown
- 1992-12-12 AT AT93900052T patent/ATE171452T1/de not_active IP Right Cessation
- 1992-12-12 CA CA002125858A patent/CA2125858A1/en not_active Abandoned
- 1992-12-12 HU HU9401877A patent/HUT66971A/hu unknown
- 1992-12-12 SK SK750-94A patent/SK75094A3/sk unknown
- 1992-12-12 NZ NZ246156A patent/NZ246156A/en unknown
- 1992-12-12 WO PCT/EP1992/002901 patent/WO1993013097A1/en not_active Ceased
- 1992-12-17 IN IN758MA1992 patent/IN174405B/en unknown
- 1992-12-18 IL IL104169A patent/IL104169A0/xx unknown
- 1992-12-22 SI SI19929200408A patent/SI9200408A/sl unknown
- 1992-12-22 MX MX9207494A patent/MX9207494A/es unknown
- 1992-12-22 HR HR921455A patent/HRP921455A2/hr not_active Application Discontinuation
-
1993
- 1993-06-22 CN CN93109454A patent/CN1096784A/zh active Pending
-
1994
- 1994-05-31 BG BG98813A patent/BG98813A/bg unknown
- 1994-06-22 NO NO942376A patent/NO942376L/no unknown
- 1994-06-22 FI FI943019A patent/FI943019A0/fi not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| FI943019A7 (fi) | 1994-06-22 |
| EP0618916B1 (en) | 1998-09-23 |
| JP2527917B2 (ja) | 1996-08-28 |
| BG98813A (bg) | 1995-05-31 |
| CN1096784A (zh) | 1994-12-28 |
| FI943019A0 (fi) | 1994-06-22 |
| AU656832B2 (en) | 1995-02-16 |
| NO942376D0 (enExample) | 1994-06-22 |
| JPH07502280A (ja) | 1995-03-09 |
| IL104169A0 (en) | 1993-05-13 |
| WO1993013097A1 (en) | 1993-07-08 |
| SI9200408A (en) | 1993-09-30 |
| CZ153594A3 (en) | 1995-02-15 |
| CA2125858A1 (en) | 1993-07-08 |
| ATE171452T1 (de) | 1998-10-15 |
| US5464781A (en) | 1995-11-07 |
| MX9207494A (es) | 1993-07-01 |
| HU9401877D0 (en) | 1994-09-28 |
| NO942376L (no) | 1994-06-22 |
| HUT66971A (en) | 1995-01-30 |
| DE69227125D1 (de) | 1998-10-29 |
| GB9127252D0 (en) | 1992-02-19 |
| NZ246156A (en) | 1996-01-26 |
| AU3158793A (en) | 1993-07-28 |
| EP0618916A1 (en) | 1994-10-12 |
| IN174405B (enExample) | 1994-11-26 |
| HRP921455A2 (en) | 1994-12-31 |
| DE69227125T2 (de) | 1999-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5464781A (en) | Amino naphthyridine compounds as anti-rhoumatic agents | |
| US5780482A (en) | Condensed 4-aminopyridines with antirheumatic activity | |
| US5747486A (en) | Thienopyridine or thienopyrimidine derivatives and their use | |
| US4753951A (en) | Condensed imidazopyridine derivatives useful as psychotropic agents | |
| DE69524114T2 (de) | Naphthyridinonderivate | |
| UA74850C2 (en) | Amide derivatives as nmda receptor antagonists | |
| WO1999028320A1 (en) | 2-aryl-8-oxodihydropurine derivatives, process for producing the same, medicinal compositions containing the same, and intermediates thereof | |
| SK280822B6 (sk) | Imidazopyridíny, spôsob ich prípravy, farmaceutické prostriedky s ich obsahom a ich použitie | |
| CZ374692A3 (en) | Proteolytic enzymes inhibitors based on saccharin derivatives | |
| CZ289573B6 (cs) | Sacharinové deriváty, farmaceutický prostředek obsahující tyto deriváty a pouľití těchto sacharinových derivátů | |
| JP2005502662A (ja) | ホスホジエステラーゼ阻害剤としての１−アルキルまたは１−シクロアルキルトリアゾロ［４，３−ａ］キナゾリン−５−オン類 | |
| JP4227197B2 (ja) | １Ｈ―ピリド［３，４―ｂ］インドール―４―カルボキサミド誘導体、その製造および治療上の適用 | |
| HU198047B (en) | Process for production of new condensated derivatives of pirrol and medical preparatives containing these compounds as active substances | |
| EP0174858B1 (en) | Isoindolinone derivatives, production and use thereof | |
| HU198048B (en) | Process for production of derivatives of imidazo-piridine and medical preparatives containing these substances | |
| NZ203217A (en) | Pyridobenzodiazepinone derivatives and pharmaceutical compositions | |
| US5102890A (en) | Pyrrole derivatives, their preparation and pharmaceutical compositions which contain them | |
| JPS6229585A (ja) | エーテル化若しくはエステル化しうるジヒドロキシ基により位置２で置換された４―ｏｈキノリンカルボン酸の新規の誘導体、その製造方法、及び医薬としてのその使用 | |
| JPH08225531A (ja) | キノリンまたはキナゾリン誘導体を含んでなる医薬およびそれに用いる新規誘導体 | |
| WO1995007909A1 (en) | Alkyl-1-alkyl-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxylates as anti-rheumatic agents | |
| JPH11279157A (ja) | バルビツール酸誘導体およびそれらからなる骨・軟骨疾患予防・治療薬 | |
| HU193727B (en) | Process for producing pyrazolo/1,5-a/pyridine derivatives | |
| JPH04103572A (ja) | ４―フェニル―２―（１―ピペラジニル）ピリジン誘導体 | |
| SI9300584A (en) | Therapeutic agents for treatment of obesity and affective disorders and processes for their preparation | |
| JPH10503782A (ja) | 新規な５Ｈ−チアゾロ［３，２−ａ］ピリミジン−５−オン誘導体 |