IL135495A - Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acid - Google Patents
Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acidInfo
- Publication number
- IL135495A IL135495A IL13549596A IL13549596A IL135495A IL 135495 A IL135495 A IL 135495A IL 13549596 A IL13549596 A IL 13549596A IL 13549596 A IL13549596 A IL 13549596A IL 135495 A IL135495 A IL 135495A
- Authority
- IL
- Israel
- Prior art keywords
- mmol
- glycine
- melting point
- carbonyl
- product
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 115
- 238000002360 preparation method Methods 0.000 title description 8
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 title description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910052801 chlorine Chemical group 0.000 claims abstract description 25
- 239000000460 chlorine Chemical group 0.000 claims abstract description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 13
- -1 carbamoyl carbamoyl carbamoyl Chemical group 0.000 claims description 107
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 15
- 150000003254 radicals Chemical class 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- KKFDJZZADQONDE-UHFFFAOYSA-N (hydridonitrato)hydroxidocarbon(.) Chemical compound O[C]=N KKFDJZZADQONDE-UHFFFAOYSA-N 0.000 claims 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
- 125000005277 alkyl imino group Chemical group 0.000 claims 1
- 150000005840 aryl radicals Chemical class 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 41
- 239000001257 hydrogen Substances 0.000 abstract description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 17
- 150000002431 hydrogen Chemical class 0.000 abstract description 17
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical class NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 138
- 238000002844 melting Methods 0.000 description 94
- 230000008018 melting Effects 0.000 description 94
- 239000000047 product Substances 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
- 239000004471 Glycine Substances 0.000 description 72
- 229960002449 glycine Drugs 0.000 description 72
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 33
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 30
- 239000003208 petroleum Substances 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 23
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 23
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 23
- 229910052794 bromium Inorganic materials 0.000 description 23
- 239000012043 crude product Substances 0.000 description 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 18
- 229910052731 fluorine Inorganic materials 0.000 description 18
- 239000011737 fluorine Substances 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 210000004185 liver Anatomy 0.000 description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 15
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 15
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 229960000443 hydrochloric acid Drugs 0.000 description 15
- 235000011167 hydrochloric acid Nutrition 0.000 description 15
- 108010035532 Collagen Proteins 0.000 description 14
- 102000008186 Collagen Human genes 0.000 description 14
- 229920001436 collagen Polymers 0.000 description 14
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 11
- JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 description 11
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- GBCAVSYHPPARHX-UHFFFAOYSA-M n'-cyclohexyl-n-[2-(4-methylmorpholin-4-ium-4-yl)ethyl]methanediimine;4-methylbenzenesulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1.C1CCCCC1N=C=NCC[N+]1(C)CCOCC1 GBCAVSYHPPARHX-UHFFFAOYSA-M 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 235000011181 potassium carbonates Nutrition 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical class ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- WJKJXKRHMUXQSL-UHFFFAOYSA-N benzyl glycinate 4-methylbenzenesulfonate salt Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.NCC(=O)OCC1=CC=CC=C1 WJKJXKRHMUXQSL-UHFFFAOYSA-N 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 229960002429 proline Drugs 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 238000005245 sintering Methods 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical class CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 7
- JHFOWEGCZWLHNW-UHFFFAOYSA-N 4-fluoro-2-methyl-1-nitrobenzene Chemical compound CC1=CC(F)=CC=C1[N+]([O-])=O JHFOWEGCZWLHNW-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 125000001624 naphthyl group Chemical group 0.000 description 6
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 239000005711 Benzoic acid Substances 0.000 description 5
- 235000010233 benzoic acid Nutrition 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000005911 haloform reaction Methods 0.000 description 5
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 5
- 239000013067 intermediate product Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- 150000001204 N-oxides Chemical class 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000036570 collagen biosynthesis Effects 0.000 description 4
- 229960002591 hydroxyproline Drugs 0.000 description 4
- HZOJBKMCYYWXAE-UHFFFAOYSA-N magnesium pentane-2,4-dione Chemical compound [Mg+2].CC(=O)CC([CH2-])=O.CC(=O)CC([CH2-])=O HZOJBKMCYYWXAE-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012286 potassium permanganate Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 description 3
- 150000005341 2-nitrobenzoic acids Chemical class 0.000 description 3
- ODWVFIWBWJXDMT-UHFFFAOYSA-N 3-(hydroxymethyl)-4-nitrophenol Chemical compound OCC1=CC(O)=CC=C1[N+]([O-])=O ODWVFIWBWJXDMT-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 108010042086 Collagen Type IV Proteins 0.000 description 3
- 102000004266 Collagen Type IV Human genes 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940113088 dimethylacetamide Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000004761 fibrosis Effects 0.000 description 3
- 230000003176 fibrotic effect Effects 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 238000005187 foaming Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 2
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 description 2
- JMGKOWLVRNNJCO-UHFFFAOYSA-N 1-(3-hydroxyquinolin-2-yl)ethanone Chemical class C1=CC=C2C=C(O)C(C(=O)C)=NC2=C1 JMGKOWLVRNNJCO-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 102000008490 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Human genes 0.000 description 2
- 108010020504 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Proteins 0.000 description 2
- GQEIKAXUKWLVPL-UHFFFAOYSA-N 2-nitro-5-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC(OC(F)(F)F)=CC=C1[N+]([O-])=O GQEIKAXUKWLVPL-UHFFFAOYSA-N 0.000 description 2
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 2
- BCRPUBPRQSGJFL-UHFFFAOYSA-N 3-(2-nitrobenzoyl)pentane-2,4-dione Chemical compound CC(=O)C(C(C)=O)C(=O)C1=CC=CC=C1[N+]([O-])=O BCRPUBPRQSGJFL-UHFFFAOYSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- BJWCXGSEOMOVMN-UHFFFAOYSA-N 3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound OC(=O)C1=NC2=CC=CC=C2C=C1OCC1=CC=CC=C1 BJWCXGSEOMOVMN-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
- RUFWBMHXSJVLHE-UHFFFAOYSA-N 4-(benzenesulfonyl)-2-methyl-1-nitrobenzene Chemical compound C1=C([N+]([O-])=O)C(C)=CC(S(=O)(=O)C=2C=CC=CC=2)=C1 RUFWBMHXSJVLHE-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 108010050808 Procollagen Proteins 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000037319 collagen production Effects 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 1
- XTGAHWLIOPRXOC-UHFFFAOYSA-N (2-nitro-5-propan-2-yloxyphenyl)methanol Chemical compound CC(C)OC1=CC=C([N+]([O-])=O)C(CO)=C1 XTGAHWLIOPRXOC-UHFFFAOYSA-N 0.000 description 1
- 125000006702 (C1-C18) alkyl group Chemical group 0.000 description 1
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 1
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- 125000006636 (C3-C8) cycloalkylcarbonyl group Chemical group 0.000 description 1
- HPFWZNWHCWZFBD-UHFFFAOYSA-N 1,1,2,2,3,3,4-heptafluorobutan-1-ol Chemical compound OC(F)(F)C(F)(F)C(F)(F)CF HPFWZNWHCWZFBD-UHFFFAOYSA-N 0.000 description 1
- CSUFEOXMCRPQBB-UHFFFAOYSA-N 1,1,2,2-tetrafluoropropan-1-ol Chemical compound CC(F)(F)C(O)(F)F CSUFEOXMCRPQBB-UHFFFAOYSA-N 0.000 description 1
- AOTWCYSQDSKAQT-UHFFFAOYSA-N 1,2-dichloro-4-methyl-5-nitrobenzene Chemical compound CC1=CC(Cl)=C(Cl)C=C1[N+]([O-])=O AOTWCYSQDSKAQT-UHFFFAOYSA-N 0.000 description 1
- HBXSEAWAXAQKRO-UHFFFAOYSA-N 1-(3-hydroxy-6-methylquinolin-2-yl)ethanone Chemical compound C1=C(C)C=C2C=C(O)C(C(=O)C)=NC2=C1 HBXSEAWAXAQKRO-UHFFFAOYSA-N 0.000 description 1
- BTOXVQJLTUMIEN-UHFFFAOYSA-N 1-(3-hydroxy-6-octoxyquinolin-2-yl)ethanone Chemical compound N1=C(C(C)=O)C(O)=CC2=CC(OCCCCCCCC)=CC=C21 BTOXVQJLTUMIEN-UHFFFAOYSA-N 0.000 description 1
- RCPPXRFOMCZWAE-UHFFFAOYSA-N 1-(3-hydroxy-6-phenoxyquinolin-2-yl)ethanone Chemical compound C1=C2C=C(O)C(C(=O)C)=NC2=CC=C1OC1=CC=CC=C1 RCPPXRFOMCZWAE-UHFFFAOYSA-N 0.000 description 1
- VIBNKESZHRSNQF-UHFFFAOYSA-N 1-(3-hydroxy-6-propan-2-yloxyquinolin-2-yl)ethanone Chemical compound N1=C(C(C)=O)C(O)=CC2=CC(OC(C)C)=CC=C21 VIBNKESZHRSNQF-UHFFFAOYSA-N 0.000 description 1
- AXRTYICXFGDBFQ-UHFFFAOYSA-N 1-(3-phenylmethoxy-6-propan-2-yloxyquinolin-2-yl)ethanone Chemical compound C=1C2=CC(OC(C)C)=CC=C2N=C(C(C)=O)C=1OCC1=CC=CC=C1 AXRTYICXFGDBFQ-UHFFFAOYSA-N 0.000 description 1
- FSOAXUWBQUKXNN-UHFFFAOYSA-N 1-(3-phenylmethoxyquinolin-2-yl)ethanone Chemical compound CC(=O)C1=NC2=CC=CC=C2C=C1OCC1=CC=CC=C1 FSOAXUWBQUKXNN-UHFFFAOYSA-N 0.000 description 1
- RBQLWHDVBKXSKU-UHFFFAOYSA-N 1-(5-phenoxy-3-phenylmethoxyquinolin-2-yl)ethanone Chemical compound C=12C=C(OCC=3C=CC=CC=3)C(C(=O)C)=NC2=CC=CC=1OC1=CC=CC=C1 RBQLWHDVBKXSKU-UHFFFAOYSA-N 0.000 description 1
- USYRXFWXMSHKKD-UHFFFAOYSA-N 1-(6-butoxy-3-hydroxyquinolin-2-yl)ethanone Chemical compound N1=C(C(C)=O)C(O)=CC2=CC(OCCCC)=CC=C21 USYRXFWXMSHKKD-UHFFFAOYSA-N 0.000 description 1
- HGKBGWPQNSFPBN-UHFFFAOYSA-N 1-(6-butoxy-3-phenylmethoxyquinolin-2-yl)ethanone Chemical compound C=1C2=CC(OCCCC)=CC=C2N=C(C(C)=O)C=1OCC1=CC=CC=C1 HGKBGWPQNSFPBN-UHFFFAOYSA-N 0.000 description 1
- HFWDFLHGKWHSTD-UHFFFAOYSA-N 1-(6-chloro-3-hydroxyquinolin-2-yl)ethanone Chemical compound C1=C(Cl)C=C2C=C(O)C(C(=O)C)=NC2=C1 HFWDFLHGKWHSTD-UHFFFAOYSA-N 0.000 description 1
- MXHDBGCOKGSBCC-UHFFFAOYSA-N 1-(6-chloro-3-phenylmethoxyquinolin-2-yl)ethanone Chemical compound CC(=O)C1=NC2=CC=C(Cl)C=C2C=C1OCC1=CC=CC=C1 MXHDBGCOKGSBCC-UHFFFAOYSA-N 0.000 description 1
- OPJCMOGNCSSKAW-UHFFFAOYSA-N 1-(6-methoxy-3-phenylmethoxyquinolin-2-yl)ethanone Chemical compound C=1C2=CC(OC)=CC=C2N=C(C(C)=O)C=1OCC1=CC=CC=C1 OPJCMOGNCSSKAW-UHFFFAOYSA-N 0.000 description 1
- RQCABDQTEGOEBW-UHFFFAOYSA-N 1-(6-octoxy-3-phenylmethoxyquinolin-2-yl)ethanone Chemical compound C=1C2=CC(OCCCCCCCC)=CC=C2N=C(C(C)=O)C=1OCC1=CC=CC=C1 RQCABDQTEGOEBW-UHFFFAOYSA-N 0.000 description 1
- ZGLJHFYNAHGIKS-UHFFFAOYSA-N 1-(7-chloro-3-hydroxyquinolin-2-yl)ethanone Chemical compound ClC1=CC=C2C=C(O)C(C(=O)C)=NC2=C1 ZGLJHFYNAHGIKS-UHFFFAOYSA-N 0.000 description 1
- ZKKXDQCLZYMNCC-UHFFFAOYSA-N 1-(7-chloro-3-phenylmethoxyquinolin-2-yl)ethanone Chemical compound CC(=O)C1=NC2=CC(Cl)=CC=C2C=C1OCC1=CC=CC=C1 ZKKXDQCLZYMNCC-UHFFFAOYSA-N 0.000 description 1
- LBJHMKIIQJOGBJ-UHFFFAOYSA-N 1-[3-hydroxy-6-(2,2,3,3,4,4,5,5-octafluoropentoxy)quinolin-2-yl]ethanone Chemical compound C1=C(OCC(F)(F)C(F)(F)C(F)(F)C(F)F)C=C2C=C(O)C(C(=O)C)=NC2=C1 LBJHMKIIQJOGBJ-UHFFFAOYSA-N 0.000 description 1
- GZAHKGWGVSRDIA-UHFFFAOYSA-N 1-[3-hydroxy-6-(3-methoxyphenoxy)quinolin-2-yl]ethanone Chemical compound COC1=CC=CC(OC=2C=C3C=C(O)C(C(C)=O)=NC3=CC=2)=C1 GZAHKGWGVSRDIA-UHFFFAOYSA-N 0.000 description 1
- OLBRBTZAYJYWNA-UHFFFAOYSA-N 1-[3-hydroxy-6-(trifluoromethoxy)quinolin-2-yl]ethanone Chemical compound C1=C(OC(F)(F)F)C=C2C=C(O)C(C(=O)C)=NC2=C1 OLBRBTZAYJYWNA-UHFFFAOYSA-N 0.000 description 1
- ITZQXKLKVGCBEU-UHFFFAOYSA-N 1-[3-hydroxy-6-[3-(trifluoromethyl)phenoxy]quinolin-2-yl]ethanone Chemical compound C1=C2C=C(O)C(C(=O)C)=NC2=CC=C1OC1=CC=CC(C(F)(F)F)=C1 ITZQXKLKVGCBEU-UHFFFAOYSA-N 0.000 description 1
- ONJCKUZFKQUDGP-UHFFFAOYSA-N 1-[3-phenylmethoxy-5-(trifluoromethoxy)quinolin-2-yl]ethanone Chemical compound CC(=O)C1=NC2=CC=CC(OC(F)(F)F)=C2C=C1OCC1=CC=CC=C1 ONJCKUZFKQUDGP-UHFFFAOYSA-N 0.000 description 1
- ZJVIUSMHMIAJNN-UHFFFAOYSA-N 1-[3-phenylmethoxy-6-[3-(trifluoromethyl)phenoxy]quinolin-2-yl]ethanone Chemical compound C1=C2C=C(OCC=3C=CC=CC=3)C(C(=O)C)=NC2=CC=C1OC1=CC=CC(C(F)(F)F)=C1 ZJVIUSMHMIAJNN-UHFFFAOYSA-N 0.000 description 1
- IAFBERKGDTYIPC-UHFFFAOYSA-N 1-[6-(2,2,3,3,4,4,5,5-octafluoropentoxy)-3-phenylmethoxyquinolin-2-yl]ethanone Chemical compound CC(=O)C1=NC2=CC=C(OCC(F)(F)C(F)(F)C(F)(F)C(F)F)C=C2C=C1OCC1=CC=CC=C1 IAFBERKGDTYIPC-UHFFFAOYSA-N 0.000 description 1
- NLDYLTHAJHYYKS-UHFFFAOYSA-N 1-[6-(3-ethoxypropoxy)-3-hydroxyquinolin-2-yl]ethanone Chemical compound N1=C(C(C)=O)C(O)=CC2=CC(OCCCOCC)=CC=C21 NLDYLTHAJHYYKS-UHFFFAOYSA-N 0.000 description 1
- OJYPDFULQJHIQB-UHFFFAOYSA-N 1-[6-(3-ethoxypropoxy)-3-phenylmethoxyquinolin-2-yl]ethanone Chemical compound C=1C2=CC(OCCCOCC)=CC=C2N=C(C(C)=O)C=1OCC1=CC=CC=C1 OJYPDFULQJHIQB-UHFFFAOYSA-N 0.000 description 1
- UUDJMNLIICNERT-UHFFFAOYSA-N 1-[6-(3-methoxyphenoxy)-3-phenylmethoxyquinolin-2-yl]ethanone Chemical compound COC1=CC=CC(OC=2C=C3C=C(OCC=4C=CC=CC=4)C(C(C)=O)=NC3=CC=2)=C1 UUDJMNLIICNERT-UHFFFAOYSA-N 0.000 description 1
- BPTCEZWFSBVDPI-UHFFFAOYSA-N 1-[6-(benzenesulfonyl)-3-hydroxyquinolin-2-yl]ethanone Chemical compound C1=C2C=C(O)C(C(=O)C)=NC2=CC=C1S(=O)(=O)C1=CC=CC=C1 BPTCEZWFSBVDPI-UHFFFAOYSA-N 0.000 description 1
- GNEJVTUTTIWISR-UHFFFAOYSA-N 1-[6-(benzenesulfonyl)-3-phenylmethoxyquinolin-2-yl]ethanone Chemical compound CC(=O)C1=NC2=CC=C(S(=O)(=O)C=3C=CC=CC=3)C=C2C=C1OCC1=CC=CC=C1 GNEJVTUTTIWISR-UHFFFAOYSA-N 0.000 description 1
- DLRCHQJGHQVZJY-UHFFFAOYSA-N 1-[7-chloro-3-hydroxy-6-(2,2,2-trifluoroethoxy)quinolin-2-yl]ethanone Chemical compound ClC1=C(OCC(F)(F)F)C=C2C=C(O)C(C(=O)C)=NC2=C1 DLRCHQJGHQVZJY-UHFFFAOYSA-N 0.000 description 1
- CMYVZXJGBZZQCJ-UHFFFAOYSA-N 1-[7-chloro-3-phenylmethoxy-6-(2,2,2-trifluoroethoxy)quinolin-2-yl]ethanone Chemical compound CC(=O)C1=NC2=CC(Cl)=C(OCC(F)(F)F)C=C2C=C1OCC1=CC=CC=C1 CMYVZXJGBZZQCJ-UHFFFAOYSA-N 0.000 description 1
- PBBZBCJJWDJPDV-UHFFFAOYSA-N 1-[7-chloro-6-(2,2,3,3,4,4,4-heptafluorobutoxy)-3-hydroxyquinolin-2-yl]ethanone Chemical compound ClC1=C(OCC(F)(F)C(F)(F)C(F)(F)F)C=C2C=C(O)C(C(=O)C)=NC2=C1 PBBZBCJJWDJPDV-UHFFFAOYSA-N 0.000 description 1
- JOZWPJGRGUOZGY-UHFFFAOYSA-N 1-bromo-3-ethoxypropane Chemical compound CCOCCCBr JOZWPJGRGUOZGY-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- DSNVDSYVELRNLU-UHFFFAOYSA-N 1-chloro-4-methyl-5-nitro-2-(2,2,2-trifluoroethoxy)benzene Chemical compound CC1=CC(OCC(F)(F)F)=C(Cl)C=C1[N+]([O-])=O DSNVDSYVELRNLU-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical class CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- HCIAAULRYYHQQS-UHFFFAOYSA-N 2-(quinoline-2-carbonylamino)acetic acid Chemical class C1=CC=CC2=NC(C(=O)NCC(=O)O)=CC=C21 HCIAAULRYYHQQS-UHFFFAOYSA-N 0.000 description 1
- LBWNRYVGBCFJDA-UHFFFAOYSA-N 2-[(3-hydroxy-6-propan-2-yloxyquinoline-2-carbonyl)amino]acetic acid Chemical compound N1=C(C(=O)NCC(O)=O)C(O)=CC2=CC(OC(C)C)=CC=C21 LBWNRYVGBCFJDA-UHFFFAOYSA-N 0.000 description 1
- IZQMRNMMPSNPJM-UHFFFAOYSA-N 2-[(3-hydroxypyridine-2-carbonyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=NC=CC=C1O IZQMRNMMPSNPJM-UHFFFAOYSA-N 0.000 description 1
- JMVWZMFXDTXDFI-UHFFFAOYSA-N 2-[(3-hydroxyquinoline-2-carbonyl)amino]acetic acid Chemical compound C1=CC=C2C=C(O)C(C(=O)NCC(=O)O)=NC2=C1 JMVWZMFXDTXDFI-UHFFFAOYSA-N 0.000 description 1
- WSICOMDXOHFXES-UHFFFAOYSA-N 2-[(5-butoxy-3-hydroxyquinoline-2-carbonyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=C(O)C=C2C(OCCCC)=CC=CC2=N1 WSICOMDXOHFXES-UHFFFAOYSA-N 0.000 description 1
- SJJSBEAYNXNSLH-UHFFFAOYSA-N 2-[(6-butoxy-3-hydroxyquinoline-2-carbonyl)amino]acetic acid Chemical compound N1=C(C(=O)NCC(O)=O)C(O)=CC2=CC(OCCCC)=CC=C21 SJJSBEAYNXNSLH-UHFFFAOYSA-N 0.000 description 1
- AIHGQOGBSILSIS-UHFFFAOYSA-N 2-[(6-hexoxy-3-hydroxyquinoline-2-carbonyl)amino]acetic acid Chemical compound N1=C(C(=O)NCC(O)=O)C(O)=CC2=CC(OCCCCCC)=CC=C21 AIHGQOGBSILSIS-UHFFFAOYSA-N 0.000 description 1
- LJVSASZQPSGZAI-UHFFFAOYSA-N 2-[(6-methoxy-3-phenylmethoxyquinoline-2-carbonyl)amino]acetic acid Chemical compound C=1C2=CC(OC)=CC=C2N=C(C(=O)NCC(O)=O)C=1OCC1=CC=CC=C1 LJVSASZQPSGZAI-UHFFFAOYSA-N 0.000 description 1
- DYDWJNJGNNLBPY-UHFFFAOYSA-N 2-[(7-chloro-3-phenylmethoxyquinoline-2-carbonyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=NC2=CC(Cl)=CC=C2C=C1OCC1=CC=CC=C1 DYDWJNJGNNLBPY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- VXZFMTNKQPTCBU-UHFFFAOYSA-N 2-[[3-hydroxy-6-(trifluoromethoxy)quinoline-2-carbonyl]amino]acetic acid Chemical compound C1=C(OC(F)(F)F)C=C2C=C(O)C(C(=O)NCC(=O)O)=NC2=C1 VXZFMTNKQPTCBU-UHFFFAOYSA-N 0.000 description 1
- AJMLBKBHGRGZRA-UHFFFAOYSA-N 2-[[6-(benzenesulfonyl)-3-hydroxyquinoline-2-carbonyl]amino]acetic acid Chemical compound C1=C2C=C(O)C(C(=O)NCC(=O)O)=NC2=CC=C1S(=O)(=O)C1=CC=CC=C1 AJMLBKBHGRGZRA-UHFFFAOYSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- UPAJHGJZTJECSC-UHFFFAOYSA-N 2-methyl-1-nitro-4-(2,2,3,3,4,4,5,5-octafluoropentoxy)benzene Chemical compound CC1=CC(OCC(F)(F)C(F)(F)C(F)(F)C(F)F)=CC=C1[N+]([O-])=O UPAJHGJZTJECSC-UHFFFAOYSA-N 0.000 description 1
- GTKUDFVFYVPIGG-UHFFFAOYSA-N 2-methyl-1-nitro-4-(2,2,3,3-tetrafluoropropoxy)benzene Chemical compound CC1=CC(OCC(F)(F)C(F)F)=CC=C1[N+]([O-])=O GTKUDFVFYVPIGG-UHFFFAOYSA-N 0.000 description 1
- CRKAFKBUDGGQAB-UHFFFAOYSA-N 2-methyl-1-nitro-4-[3-(trifluoromethyl)phenoxy]benzene Chemical compound C1=C([N+]([O-])=O)C(C)=CC(OC=2C=C(C=CC=2)C(F)(F)F)=C1 CRKAFKBUDGGQAB-UHFFFAOYSA-N 0.000 description 1
- COHVZTXZLIRSTM-UHFFFAOYSA-N 2-methyl-1-nitro-4-phenoxybenzene Chemical compound C1=C([N+]([O-])=O)C(C)=CC(OC=2C=CC=CC=2)=C1 COHVZTXZLIRSTM-UHFFFAOYSA-N 0.000 description 1
- XNZIISMDVPNKIU-UHFFFAOYSA-N 2-methyl-1-nitro-4-phenylsulfanylbenzene Chemical compound C1=C([N+]([O-])=O)C(C)=CC(SC=2C=CC=CC=2)=C1 XNZIISMDVPNKIU-UHFFFAOYSA-N 0.000 description 1
- JVPZKFKKGZYVAD-UHFFFAOYSA-N 2-nitro-5-[3-(trifluoromethyl)phenoxy]benzoic acid Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(OC=2C=C(C=CC=2)C(F)(F)F)=C1 JVPZKFKKGZYVAD-UHFFFAOYSA-N 0.000 description 1
- ZUJJBPSUSBXVRI-UHFFFAOYSA-N 2-nitro-5-octoxybenzoic acid Chemical compound CCCCCCCCOC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 ZUJJBPSUSBXVRI-UHFFFAOYSA-N 0.000 description 1
- ZSNNELPPGKIDBW-UHFFFAOYSA-N 2-nitro-5-phenoxybenzoic acid Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(OC=2C=CC=CC=2)=C1 ZSNNELPPGKIDBW-UHFFFAOYSA-N 0.000 description 1
- MHNZLVZHPKIHLO-UHFFFAOYSA-N 2-nitro-5-propan-2-yloxybenzoic acid Chemical compound CC(C)OC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 MHNZLVZHPKIHLO-UHFFFAOYSA-N 0.000 description 1
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical class OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 1
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- IZQDHXOJQGUDDO-UHFFFAOYSA-N 3-(2-nitro-5-octoxybenzoyl)pentane-2,4-dione Chemical compound CCCCCCCCOC1=CC=C([N+]([O-])=O)C(C(=O)C(C(C)=O)C(C)=O)=C1 IZQDHXOJQGUDDO-UHFFFAOYSA-N 0.000 description 1
- YGCGSZLOVGDRCS-UHFFFAOYSA-N 3-(2-nitro-5-phenoxybenzoyl)pentane-2,4-dione Chemical compound C1=C([N+]([O-])=O)C(C(=O)C(C(C)=O)C(=O)C)=CC(OC=2C=CC=CC=2)=C1 YGCGSZLOVGDRCS-UHFFFAOYSA-N 0.000 description 1
- IBEBVLNXSUBPDU-UHFFFAOYSA-N 3-(2-nitro-5-propan-2-yloxybenzoyl)pentane-2,4-dione Chemical compound CC(C)OC1=CC=C([N+]([O-])=O)C(C(=O)C(C(C)=O)C(C)=O)=C1 IBEBVLNXSUBPDU-UHFFFAOYSA-N 0.000 description 1
- IAJLVVBHVJPJIU-UHFFFAOYSA-N 3-(4-chloro-2-nitrobenzoyl)pentane-2,4-dione Chemical compound CC(=O)C(C(C)=O)C(=O)C1=CC=C(Cl)C=C1[N+]([O-])=O IAJLVVBHVJPJIU-UHFFFAOYSA-N 0.000 description 1
- AURDQYMQRHNONV-UHFFFAOYSA-N 3-(5-butoxy-2-nitrobenzoyl)pentane-2,4-dione Chemical compound CCCCOC1=CC=C([N+]([O-])=O)C(C(=O)C(C(C)=O)C(C)=O)=C1 AURDQYMQRHNONV-UHFFFAOYSA-N 0.000 description 1
- PJLKABHSDZUXAG-UHFFFAOYSA-N 3-(5-methoxy-2-nitrobenzoyl)pentane-2,4-dione Chemical compound COC1=CC=C([N+]([O-])=O)C(C(=O)C(C(C)=O)C(C)=O)=C1 PJLKABHSDZUXAG-UHFFFAOYSA-N 0.000 description 1
- OKPFIWIMBJNFSE-UHFFFAOYSA-N 3-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=CC(OC(F)(F)F)=C1 OKPFIWIMBJNFSE-UHFFFAOYSA-N 0.000 description 1
- VEACYYUVQDTTPK-UHFFFAOYSA-N 3-[2-nitro-5-(2,2,3,3-tetrafluoropropoxy)benzoyl]pentane-2,4-dione Chemical compound CC(=O)C(C(C)=O)C(=O)C1=CC(OCC(F)(F)C(F)F)=CC=C1[N+]([O-])=O VEACYYUVQDTTPK-UHFFFAOYSA-N 0.000 description 1
- QLYRBTFMWLIFIZ-UHFFFAOYSA-N 3-[2-nitro-5-(trifluoromethoxy)benzoyl]pentane-2,4-dione Chemical compound CC(=O)C(C(C)=O)C(=O)C1=CC(OC(F)(F)F)=CC=C1[N+]([O-])=O QLYRBTFMWLIFIZ-UHFFFAOYSA-N 0.000 description 1
- MFFNVKOPHZDHJU-UHFFFAOYSA-N 3-[2-nitro-5-[3-(trifluoromethyl)phenoxy]benzoyl]pentane-2,4-dione Chemical compound C1=C([N+]([O-])=O)C(C(=O)C(C(C)=O)C(=O)C)=CC(OC=2C=C(C=CC=2)C(F)(F)F)=C1 MFFNVKOPHZDHJU-UHFFFAOYSA-N 0.000 description 1
- QTTMCNKNXNEBGY-UHFFFAOYSA-N 3-[4-chloro-2-nitro-5-(2,2,2-trifluoroethoxy)benzoyl]pentane-2,4-dione Chemical compound CC(=O)C(C(C)=O)C(=O)C1=CC(OCC(F)(F)F)=C(Cl)C=C1[N+]([O-])=O QTTMCNKNXNEBGY-UHFFFAOYSA-N 0.000 description 1
- SCNXHHHNXDXYHM-UHFFFAOYSA-N 3-[4-chloro-5-(2,2,3,3,4,4,4-heptafluorobutoxy)-2-nitrobenzoyl]pentane-2,4-dione Chemical compound CC(=O)C(C(C)=O)C(=O)C1=CC(OCC(F)(F)C(F)(F)C(F)(F)F)=C(Cl)C=C1[N+]([O-])=O SCNXHHHNXDXYHM-UHFFFAOYSA-N 0.000 description 1
- KRJWQEGZEFOEEJ-UHFFFAOYSA-N 3-[5-(3-methoxyphenoxy)-2-nitrobenzoyl]pentane-2,4-dione Chemical compound COC1=CC=CC(OC=2C=C(C(=CC=2)[N+]([O-])=O)C(=O)C(C(C)=O)C(C)=O)=C1 KRJWQEGZEFOEEJ-UHFFFAOYSA-N 0.000 description 1
- UFGPLAZCYJEIRY-UHFFFAOYSA-N 3-[5-(benzenesulfonyl)-2-nitrobenzoyl]pentane-2,4-dione Chemical compound C1=C([N+]([O-])=O)C(C(=O)C(C(C)=O)C(=O)C)=CC(S(=O)(=O)C=2C=CC=CC=2)=C1 UFGPLAZCYJEIRY-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- XHMWPVBQGARKQM-UHFFFAOYSA-N 3-ethoxy-1-propanol Chemical compound CCOCCCO XHMWPVBQGARKQM-UHFFFAOYSA-N 0.000 description 1
- SOYBEXQHNURCGE-UHFFFAOYSA-N 3-ethoxypropan-1-amine Chemical compound CCOCCCN SOYBEXQHNURCGE-UHFFFAOYSA-N 0.000 description 1
- WTRAGVLPOKIUTD-UHFFFAOYSA-N 3-hydroxy-6-methoxyquinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C(O)=CC2=CC(OC)=CC=C21 WTRAGVLPOKIUTD-UHFFFAOYSA-N 0.000 description 1
- WHKZBVQIMVUGIH-UHFFFAOYSA-N 3-hydroxyquinoline-2-carboxylic acid Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=NC2=C1 WHKZBVQIMVUGIH-UHFFFAOYSA-N 0.000 description 1
- CSSULASVGGUFAV-UHFFFAOYSA-N 3-phenylmethoxy-6-[3-(trifluoromethyl)phenoxy]quinoline-2-carboxylic acid Chemical compound C1=C2C=C(OCC=3C=CC=CC=3)C(C(=O)O)=NC2=CC=C1OC1=CC=CC(C(F)(F)F)=C1 CSSULASVGGUFAV-UHFFFAOYSA-N 0.000 description 1
- DUJTYONPTYGXKW-UHFFFAOYSA-N 3-phenylmethoxy-6-propan-2-yloxyquinoline-2-carboxylic acid Chemical compound C=1C2=CC(OC(C)C)=CC=C2N=C(C(O)=O)C=1OCC1=CC=CC=C1 DUJTYONPTYGXKW-UHFFFAOYSA-N 0.000 description 1
- SMJYMTQQYUQMDX-UHFFFAOYSA-N 4-(3-methoxyphenoxy)-2-methyl-1-nitrobenzene Chemical compound COC1=CC=CC(OC=2C=C(C)C(=CC=2)[N+]([O-])=O)=C1 SMJYMTQQYUQMDX-UHFFFAOYSA-N 0.000 description 1
- QGBJRGFUHWUVHT-UHFFFAOYSA-N 4-chloro-2-nitro-5-(2,2,2-trifluoroethoxy)benzoic acid Chemical compound OC(=O)C1=CC(OCC(F)(F)F)=C(Cl)C=C1[N+]([O-])=O QGBJRGFUHWUVHT-UHFFFAOYSA-N 0.000 description 1
- JAHIPDTWWVYVRV-UHFFFAOYSA-N 4-chloro-2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1[N+]([O-])=O JAHIPDTWWVYVRV-UHFFFAOYSA-N 0.000 description 1
- LHMGTCOSAXENPT-UHFFFAOYSA-N 4-chloro-5-(2,2,3,3,4,4,4-heptafluorobutoxy)-2-nitrobenzoic acid Chemical compound OC(=O)C1=CC(OCC(F)(F)C(F)(F)C(F)(F)F)=C(Cl)C=C1[N+]([O-])=O LHMGTCOSAXENPT-UHFFFAOYSA-N 0.000 description 1
- ROUNLYFUNZAGCZ-UHFFFAOYSA-N 5-(3-ethoxypropoxy)-2-nitrobenzoic acid Chemical compound CCOCCCOC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 ROUNLYFUNZAGCZ-UHFFFAOYSA-N 0.000 description 1
- BVNBROPUSFUBTD-UHFFFAOYSA-N 5-(3-methoxyphenoxy)-2-nitrobenzoic acid Chemical compound COC1=CC=CC(OC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 BVNBROPUSFUBTD-UHFFFAOYSA-N 0.000 description 1
- XCXZXXAUKQKWOJ-UHFFFAOYSA-N 5-(benzenesulfonyl)-2-nitrobenzoic acid Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(S(=O)(=O)C=2C=CC=CC=2)=C1 XCXZXXAUKQKWOJ-UHFFFAOYSA-N 0.000 description 1
- NXORGPAOMLHVFM-UHFFFAOYSA-N 5-butoxy-2-nitrobenzoic acid Chemical compound CCCCOC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 NXORGPAOMLHVFM-UHFFFAOYSA-N 0.000 description 1
- KVYNESAFSIBRCS-UHFFFAOYSA-N 5-butoxy-2-nitrobenzoyl chloride Chemical compound CCCCOC1=CC=C([N+]([O-])=O)C(C(Cl)=O)=C1 KVYNESAFSIBRCS-UHFFFAOYSA-N 0.000 description 1
- URADKXVAIGMTEG-UHFFFAOYSA-N 5-methoxy-2-nitrobenzoic acid Chemical compound COC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 URADKXVAIGMTEG-UHFFFAOYSA-N 0.000 description 1
- FRGGQUVDTHUMMK-UHFFFAOYSA-N 6-(2,2,3,3,4,4,5,5-octafluoropentoxy)-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound OC(=O)C1=NC2=CC=C(OCC(F)(F)C(F)(F)C(F)(F)C(F)F)C=C2C=C1OCC1=CC=CC=C1 FRGGQUVDTHUMMK-UHFFFAOYSA-N 0.000 description 1
- BENVFGBIDCGSKT-UHFFFAOYSA-N 6-(3-ethoxypropoxy)-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound C=1C2=CC(OCCCOCC)=CC=C2N=C(C(O)=O)C=1OCC1=CC=CC=C1 BENVFGBIDCGSKT-UHFFFAOYSA-N 0.000 description 1
- HUTNVLYDHNTBDL-UHFFFAOYSA-N 6-(3-methoxyphenoxy)-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound COC1=CC=CC(OC=2C=C3C=C(OCC=4C=CC=CC=4)C(C(O)=O)=NC3=CC=2)=C1 HUTNVLYDHNTBDL-UHFFFAOYSA-N 0.000 description 1
- NRHPTOQENPWDHT-UHFFFAOYSA-N 6-(benzenesulfonyl)-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound OC(=O)C1=NC2=CC=C(S(=O)(=O)C=3C=CC=CC=3)C=C2C=C1OCC1=CC=CC=C1 NRHPTOQENPWDHT-UHFFFAOYSA-N 0.000 description 1
- HIYIPXNUSSBSNP-UHFFFAOYSA-N 6-butoxy-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound C=1C2=CC(OCCCC)=CC=C2N=C(C(O)=O)C=1OCC1=CC=CC=C1 HIYIPXNUSSBSNP-UHFFFAOYSA-N 0.000 description 1
- QNMBNENFFCUPRG-UHFFFAOYSA-N 6-chloro-1-(2,2,3,3,4,4,4-heptafluorobutoxy)-3-methyl-6-nitrocyclohexa-1,3-diene Chemical compound CC1=CCC(Cl)([N+]([O-])=O)C(OCC(F)(F)C(F)(F)C(F)(F)F)=C1 QNMBNENFFCUPRG-UHFFFAOYSA-N 0.000 description 1
- WUIZVBDCSFZMDI-UHFFFAOYSA-N 6-chloro-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound OC(=O)C1=NC2=CC=C(Cl)C=C2C=C1OCC1=CC=CC=C1 WUIZVBDCSFZMDI-UHFFFAOYSA-N 0.000 description 1
- PUTAOZJNFRWAIA-UHFFFAOYSA-N 6-methoxy-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound C=1C2=CC(OC)=CC=C2N=C(C(O)=O)C=1OCC1=CC=CC=C1 PUTAOZJNFRWAIA-UHFFFAOYSA-N 0.000 description 1
- LAQXAOSDCQIDBE-UHFFFAOYSA-N 6-octoxy-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound C=1C2=CC(OCCCCCCCC)=CC=C2N=C(C(O)=O)C=1OCC1=CC=CC=C1 LAQXAOSDCQIDBE-UHFFFAOYSA-N 0.000 description 1
- XGHREJRCUZSTPV-UHFFFAOYSA-N 6-phenoxy-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound C1=C2C=C(OCC=3C=CC=CC=3)C(C(=O)O)=NC2=CC=C1OC1=CC=CC=C1 XGHREJRCUZSTPV-UHFFFAOYSA-N 0.000 description 1
- ODMOKSXCVPXLGL-UHFFFAOYSA-N 7-chloro-3-phenylmethoxyquinoline-2-carboxylic acid Chemical compound OC(=O)C1=NC2=CC(Cl)=CC=C2C=C1OCC1=CC=CC=C1 ODMOKSXCVPXLGL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- WFLOFEOFRYPJED-UHFFFAOYSA-N CC(=O)CC([CH2-])=O Chemical compound CC(=O)CC([CH2-])=O WFLOFEOFRYPJED-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 102000001187 Collagen Type III Human genes 0.000 description 1
- 108010069502 Collagen Type III Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 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 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- BIMZLRFONYSTPT-UHFFFAOYSA-N N-oxalylglycine Chemical class OC(=O)CNC(=O)C(O)=O BIMZLRFONYSTPT-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- BWFJUMITJBCAOB-UHFFFAOYSA-N O1CCCC1.NCC(=O)O Chemical compound O1CCCC1.NCC(=O)O BWFJUMITJBCAOB-UHFFFAOYSA-N 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical class C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 238000007351 Smiles rearrangement reaction Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 231100000644 Toxic injury Toxicity 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 150000008062 acetophenones Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
- 229960002576 amiloride Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940093740 amino acid and derivative Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000012736 aqueous medium 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
- 238000003556 assay Methods 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- 150000001559 benzoic acids Chemical class 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- DZZPNUGSSGDLRA-UHFFFAOYSA-N benzyl 2-[(3-phenylmethoxyquinoline-2-carbonyl)amino]acetate Chemical compound C=1C=CC=CC=1COC(=O)CNC(=O)C1=NC2=CC=CC=C2C=C1OCC1=CC=CC=C1 DZZPNUGSSGDLRA-UHFFFAOYSA-N 0.000 description 1
- ZXYZNCOTGJZJEQ-UHFFFAOYSA-N benzyl 2-[(6-phenoxy-3-phenylmethoxyquinoline-2-carbonyl)amino]acetate Chemical compound C=1C=CC=CC=1COC(=O)CNC(=O)C(C(=CC1=C2)OCC=3C=CC=CC=3)=NC1=CC=C2OC1=CC=CC=C1 ZXYZNCOTGJZJEQ-UHFFFAOYSA-N 0.000 description 1
- GNYXENYSXWGRCO-UHFFFAOYSA-N benzyl 2-[[4-(2,2,3,3,4,4,5,5-octafluoropentoxy)-3-phenylmethoxyquinoline-2-carbonyl]amino]acetate Chemical compound C=1C=CC=CC=1COC(=O)CNC(=O)C1=NC2=CC=CC=C2C(OCC(F)(F)C(F)(F)C(F)(F)C(F)F)=C1OCC1=CC=CC=C1 GNYXENYSXWGRCO-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003865 brosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)S(*)(=O)=O 0.000 description 1
- XNFCYMKARKEMCX-UHFFFAOYSA-N butyl 2-[(6-methoxy-3-phenylmethoxyquinoline-2-carbonyl)amino]acetate Chemical compound CCCCOC(=O)CNC(=O)C1=NC2=CC=C(OC)C=C2C=C1OCC1=CC=CC=C1 XNFCYMKARKEMCX-UHFFFAOYSA-N 0.000 description 1
- NFCPBBXWCPNVDP-UHFFFAOYSA-N butyl 2-aminoacetate;4-methylbenzenesulfonic acid Chemical compound CCCCOC(=O)CN.CC1=CC=C(S(O)(=O)=O)C=C1 NFCPBBXWCPNVDP-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 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 1
- 230000006378 damage Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- FHIRJIOFMONBEJ-UHFFFAOYSA-N ethyl 2-[(7-chloro-3-phenylmethoxyquinoline-2-carbonyl)amino]acetate Chemical compound CCOC(=O)CNC(=O)C1=NC2=CC(Cl)=CC=C2C=C1OCC1=CC=CC=C1 FHIRJIOFMONBEJ-UHFFFAOYSA-N 0.000 description 1
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 1
- AWAHFDRYDUSDQG-UHFFFAOYSA-N ethyl 3-(4-methylphenyl)sulfonyloxyquinoline-2-carboxylate Chemical compound CCOC(=O)C1=NC2=CC=CC=C2C=C1OS(=O)(=O)C1=CC=C(C)C=C1 AWAHFDRYDUSDQG-UHFFFAOYSA-N 0.000 description 1
- YEMPERUHXORKOO-UHFFFAOYSA-N ethyl 3-hydroxyquinoline-2-carboxylate Chemical compound C1=CC=C2C=C(O)C(C(=O)OCC)=NC2=C1 YEMPERUHXORKOO-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical class NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
- 229960001269 glycine hydrochloride Drugs 0.000 description 1
- 210000000208 hepatic perisinusoidal cell Anatomy 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000008011 inorganic excipient Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004890 malting Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229940057952 methanol Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- ZDIVCPODDCJMDM-UHFFFAOYSA-N methyl 3-methoxyquinoline-2-carboxylate Chemical compound C1=CC=C2C=C(OC)C(C(=O)OC)=NC2=C1 ZDIVCPODDCJMDM-UHFFFAOYSA-N 0.000 description 1
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- SATVIFGJTRRDQU-UHFFFAOYSA-N potassium hypochlorite Chemical compound [K+].Cl[O-] SATVIFGJTRRDQU-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012262 resinous product Substances 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 150000003613 toluenes Chemical class 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Electroluminescent Light Sources (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19536263A DE19536263A1 (de) | 1995-09-28 | 1995-09-28 | Substituierte Chinolin-2-carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE19605170 | 1996-02-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL135495A true IL135495A (en) | 2002-12-01 |
Family
ID=26019051
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13549596A IL135495A (en) | 1995-09-28 | 1996-06-29 | Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acid |
| IL11930296A IL119302A0 (en) | 1995-09-28 | 1996-09-26 | Substituted quinoline-2-carboxylic acid amides their preparation and their use as medicaments and intermediate products |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL11930296A IL119302A0 (en) | 1995-09-28 | 1996-09-26 | Substituted quinoline-2-carboxylic acid amides their preparation and their use as medicaments and intermediate products |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US5726305A (fr) |
| EP (1) | EP0765871B1 (fr) |
| JP (1) | JPH09124606A (fr) |
| KR (1) | KR970061869A (fr) |
| CN (2) | CN1120157C (fr) |
| AT (1) | ATE263155T1 (fr) |
| AU (1) | AU728208B2 (fr) |
| CA (1) | CA2186717A1 (fr) |
| CZ (1) | CZ283396A3 (fr) |
| DE (1) | DE59610950D1 (fr) |
| ES (1) | ES2215184T3 (fr) |
| HU (1) | HUP9602685A3 (fr) |
| IL (2) | IL135495A (fr) |
| MX (1) | MX9604378A (fr) |
| MY (1) | MY133647A (fr) |
| NO (1) | NO308600B1 (fr) |
| NZ (1) | NZ299455A (fr) |
| PL (1) | PL316321A1 (fr) |
| SG (1) | SG45503A1 (fr) |
| SI (1) | SI9600287A (fr) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19650215A1 (de) * | 1996-12-04 | 1998-06-10 | Hoechst Ag | 3-Hydroxypyridin-2-carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE19746287A1 (de) * | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| US20020198145A1 (en) * | 1999-06-10 | 2002-12-26 | Cognetix, Inc. | MuO-conopeptides and their use as local anesthetics |
| CA2432642A1 (fr) * | 2000-12-21 | 2002-08-08 | Subhash P. Khanapure | Composes aryle substitues en tant que nouveaux inhibiteurs selectifs de la cyclo-oxygenase-2, compositions et methodes d'utilisation |
| US20040146964A1 (en) * | 2001-03-21 | 2004-07-29 | Maxwell Patrick Henry | Assays, methods and means |
| EP2295060B1 (fr) | 2001-12-06 | 2018-10-31 | Fibrogen, Inc. | Traitement de conditions ischémiques ou hypoxiques |
| CN100522946C (zh) | 2001-12-06 | 2009-08-05 | 法布罗根股份有限公司 | 低氧诱导因子(HIF)α的稳定化 |
| US7618940B2 (en) | 2002-12-06 | 2009-11-17 | Fibrogen, Inc. | Fat regulation |
| US8124582B2 (en) * | 2002-12-06 | 2012-02-28 | Fibrogen, Inc. | Treatment of diabetes |
| PT1644336E (pt) * | 2003-06-06 | 2011-04-21 | Fibrogen Inc | Compostos de heteroarilo que contêm azoto e sua utilização no aumento da eritropoetina endógena |
| US8614204B2 (en) * | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
| WO2005034929A2 (fr) * | 2003-10-10 | 2005-04-21 | Fibrogen, Inc. | Remodelage et vascularisation de tissus |
| EP1893186A2 (fr) * | 2005-06-06 | 2008-03-05 | Fibrogen, Inc. | Methode amelioree de traitement de l'anemie |
| WO2006138511A2 (fr) | 2005-06-15 | 2006-12-28 | Fibrogen, Inc. | Composes et procedes pour le traitement du cancer |
| WO2007025798A2 (fr) | 2005-07-27 | 2007-03-08 | F. Hoffmann-La Roche Ag | Aryloxy quinolines et leur utilisation en tant que 5-ht6 |
| US7728130B2 (en) * | 2005-12-09 | 2010-06-01 | Amgen Inc. | Quinolone based compounds exhibiting prolyl hydroxylase inhibitory activity |
| JP5161793B2 (ja) * | 2006-01-27 | 2013-03-13 | フィブロジェン， インコーポレイテッド | 低酸素症誘導因子（ｈｉｆ）を安定化するシアノイソキノリン化合物 |
| WO2007101204A1 (fr) * | 2006-02-27 | 2007-09-07 | Alcon Research, Ltd. | Méthode de traitement du glaucome |
| US7745461B1 (en) | 2006-02-27 | 2010-06-29 | Alcon Research, Ltd. | Method of treating dry eye disorders |
| ES2533765T3 (es) * | 2006-03-30 | 2015-04-15 | Lg Electronics Inc. | Un método y un aparato para descodificar/codificar una señal de video |
| CN103497184A (zh) * | 2006-04-04 | 2014-01-08 | 菲布罗根有限公司 | 作为hif调节剂的吡咯并吡啶和噻唑并吡啶化合物 |
| EP4095127A1 (fr) | 2006-06-26 | 2022-11-30 | Akebia Therapeutics Inc. | Inhibiteurs de prolyl hydroxylase et procédés d'utilisation |
| EP2111399A2 (fr) * | 2006-12-18 | 2009-10-28 | Amgen Inc. | Composés de naphtalénone présentant une activité inhibititrice de prolyle hydroxylase, compositions et utilisations de ceux-ci |
| US8048892B2 (en) * | 2006-12-18 | 2011-11-01 | Amgen Inc. | Azaquinolone based compounds exhibiting prolyl hydroxylase inhibitory activity, compositions, and uses thereof |
| CA2683956C (fr) * | 2007-04-18 | 2012-12-18 | Amgen Inc. | Quinolones et azaquinolones inhibant la prolyl hydroxylase |
| US7569726B2 (en) * | 2007-04-18 | 2009-08-04 | Amgen Inc. | Indanone derivatives that inhibit prolyl hydroxylase |
| WO2008137084A2 (fr) * | 2007-05-04 | 2008-11-13 | Amgen Inc. | Diazaquinolones inhibant l'activité de la prolyl hydroxylase |
| ES2389063T3 (es) * | 2007-05-04 | 2012-10-22 | Amgen, Inc | Derivados de tienopiridina y tiazolopiridina que inhiben la actividad prolil hidroxilasa |
| WO2009002533A1 (fr) * | 2007-06-27 | 2008-12-31 | The Brigham And Women's Hospital, Inc. | Thérapies d'affection abdominale inflammatoire |
| AU2009314155B2 (en) | 2008-11-14 | 2015-10-08 | Fibrogen, Inc. | Thiochromene derivatives as HIF hydroxylase inhibitors |
| UA107360C2 (en) | 2009-08-05 | 2014-12-25 | Biogen Idec Inc | Bicyclic aryl sphingosine 1-phosphate analogs |
| ES2575154T3 (es) * | 2009-12-17 | 2016-06-24 | Merck Sharp & Dohme Corp. | Moduladores alostéricos positivos del receptor M1 de quinolina amida |
| DK2672823T3 (en) | 2011-02-07 | 2016-11-28 | Biogen Ma Inc | S1P-modulating agents |
| NO2686520T3 (fr) | 2011-06-06 | 2018-03-17 | ||
| CN104470899B (zh) | 2012-03-09 | 2017-12-26 | 菲布罗根有限公司 | 作为hif羟化酶抑制剂的4‑羟基‑异喹啉化合物 |
| MY171483A (en) | 2012-07-16 | 2019-10-15 | Fibrogen Inc | Process for making isoquinoline compounds |
| US8883823B2 (en) | 2012-07-16 | 2014-11-11 | Fibrogen, Inc. | Crystalline forms of a prolyl hydroxylase inhibitor |
| ES2905898T3 (es) | 2012-07-16 | 2022-04-12 | Fibrogen Inc | Formas cristalinas de un inhibidor de prolil hidroxilasa |
| SG11201500339XA (en) * | 2012-07-27 | 2015-02-27 | Biogen Ma Inc | Atx modulating agents |
| RU2666144C2 (ru) | 2013-01-24 | 2018-09-06 | Фиброген, Инк. | Кристаллические формы { [1-циано-5-(4-хлорофенокси)-4-гидроксиизохинолин-3-карбонил]-амино} -уксусной кислоты |
| BR112015031027A2 (pt) | 2013-06-13 | 2017-08-29 | Akebia Therapeutics Inc | Uso de um composto, método in vitro, composição farmacêutica e forma de dosagem única |
| MX2021001169A (es) | 2013-11-15 | 2023-02-10 | Akebia Therapeutics Inc | Formas sólidas de ácido {[5-(3-clorofenil)-3-hidroxipiridin-2-carb onil]amino}acético, composiciones, y usos de las mismas. |
| BR112017015852A2 (pt) | 2015-01-23 | 2018-03-27 | Akebia Therapeutics Inc | forma de cristal, sal hemicálcico, sal hemicálcico di-hidratado, sal monossódico hidratado, sal bissódico monoidratado, sal monossódico anidro e método para preparar o composto 1 |
| IL292262B2 (en) | 2015-04-01 | 2024-02-01 | Akebia Therapeutics Inc | Formulation of an oral administration form of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid |
| MX2020011845A (es) | 2018-05-09 | 2021-01-15 | Akebia Therapeutics Inc | Proceso para preparar acido 2-[[5-(3-clorofenil)-3-hidroxipiridina -2-carbonil]amino]acetico. |
| CN113302175A (zh) | 2018-11-09 | 2021-08-24 | 维瓦斯治疗公司 | 双环化合物 |
| CN114072207B (zh) | 2019-04-16 | 2024-03-29 | 维瓦斯治疗公司 | 双环化合物 |
| US11524939B2 (en) | 2019-11-13 | 2022-12-13 | Akebia Therapeutics, Inc. | Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4015255A1 (de) * | 1990-05-12 | 1991-11-14 | Hoechst Ag | Oxalyl-aminosaeurederivate, verfahren zu ihrer herstellung und ihrer verwendung als arzneimittel zur inhibierung der prolyl-hydroxylase |
| US5192773A (en) * | 1990-07-02 | 1993-03-09 | Vertex Pharmaceuticals, Inc. | Immunosuppressive compounds |
| EP0541042A1 (fr) * | 1991-11-05 | 1993-05-12 | Hoechst Aktiengesellschaft | Dérivés d'acide pyridine 2,4- et 2,5-dicarboxyliques, leur procédé de préparation et leur utilisation comme médicaments |
| TW352384B (en) * | 1992-03-24 | 1999-02-11 | Hoechst Ag | Sulfonamido- or sulfonamidocarbonylpyridine-2-carboxamides, process for their preparation and their use as pharmaceuticals |
| DE4233124A1 (de) * | 1992-10-02 | 1994-04-07 | Hoechst Ag | Acylsulfonamido- und Sulfonamidopyridin-2-carbonsäureester sowie ihre Pyridin-N-oxide, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DK122693D0 (da) * | 1993-10-29 | 1993-10-29 | Hempels Skibsfarve Fab J C | Marin struktur |
| EP0650960B1 (fr) * | 1993-11-02 | 1997-03-05 | Hoechst Aktiengesellschaft | Esters de carboxamide hétérocycliques substitués, leur préparation et leur utilisation comme médicaments |
| DE59401924D1 (de) * | 1993-11-02 | 1997-04-10 | Hoechst Ag | Substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| NZ270267A (en) * | 1993-12-30 | 1997-03-24 | Hoechst Ag | 3-hydroxypyridin-2yl (and -quinolin-2-yl) carboxamide derivatives and pharmaceutical compositions |
-
1996
- 1996-06-29 IL IL13549596A patent/IL135495A/en not_active IP Right Cessation
- 1996-07-03 US US08/675,155 patent/US5726305A/en not_active Expired - Lifetime
- 1996-07-03 US US08/675,208 patent/US5719164A/en not_active Expired - Lifetime
- 1996-09-20 EP EP96115110A patent/EP0765871B1/fr not_active Expired - Lifetime
- 1996-09-20 AT AT96115110T patent/ATE263155T1/de not_active IP Right Cessation
- 1996-09-20 ES ES96115110T patent/ES2215184T3/es not_active Expired - Lifetime
- 1996-09-20 DE DE59610950T patent/DE59610950D1/de not_active Expired - Lifetime
- 1996-09-25 KR KR1019960042606A patent/KR970061869A/ko not_active Application Discontinuation
- 1996-09-26 NZ NZ299455A patent/NZ299455A/en unknown
- 1996-09-26 CZ CZ962833A patent/CZ283396A3/cs unknown
- 1996-09-26 CN CN96122806A patent/CN1120157C/zh not_active Expired - Lifetime
- 1996-09-26 AU AU65838/96A patent/AU728208B2/en not_active Ceased
- 1996-09-26 IL IL11930296A patent/IL119302A0/xx unknown
- 1996-09-27 SG SG1996010735A patent/SG45503A1/en unknown
- 1996-09-27 SI SI9600287A patent/SI9600287A/sl unknown
- 1996-09-27 MY MYPI96004023A patent/MY133647A/en unknown
- 1996-09-27 CA CA002186717A patent/CA2186717A1/fr not_active Abandoned
- 1996-09-27 NO NO964093A patent/NO308600B1/no not_active IP Right Cessation
- 1996-09-27 MX MX9604378A patent/MX9604378A/es unknown
- 1996-09-27 HU HU9602685A patent/HUP9602685A3/hu unknown
- 1996-09-27 PL PL96316321A patent/PL316321A1/xx unknown
- 1996-09-30 JP JP8276901A patent/JPH09124606A/ja active Pending
-
2000
- 2000-06-14 CN CN00118801A patent/CN1282737A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HUP9602685A2 (hu) | 1998-09-28 |
| CA2186717A1 (fr) | 1997-03-29 |
| CN1282737A (zh) | 2001-02-07 |
| JPH09124606A (ja) | 1997-05-13 |
| NO308600B1 (no) | 2000-10-02 |
| EP0765871A1 (fr) | 1997-04-02 |
| MX9604378A (es) | 1997-03-29 |
| AU728208B2 (en) | 2001-01-04 |
| HUP9602685A3 (en) | 2001-04-28 |
| IL119302A0 (en) | 1996-12-05 |
| US5726305A (en) | 1998-03-10 |
| CN1154365A (zh) | 1997-07-16 |
| CZ283396A3 (en) | 1997-04-16 |
| EP0765871B1 (fr) | 2004-03-31 |
| KR970061869A (ko) | 1997-09-12 |
| MY133647A (en) | 2007-11-30 |
| NO964093L (no) | 1997-04-01 |
| NO964093D0 (no) | 1996-09-27 |
| DE59610950D1 (de) | 2004-05-06 |
| NZ299455A (en) | 1997-06-24 |
| CN1120157C (zh) | 2003-09-03 |
| ATE263155T1 (de) | 2004-04-15 |
| AU6583896A (en) | 1997-04-10 |
| HU9602685D0 (en) | 1996-11-28 |
| PL316321A1 (en) | 1997-04-01 |
| SG45503A1 (en) | 1998-01-16 |
| US5719164A (en) | 1998-02-17 |
| SI9600287A (en) | 1997-04-30 |
| ES2215184T3 (es) | 2004-10-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| IL135495A (en) | Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acid | |
| US5620995A (en) | Substituted heterocyclic carboxyamides, their preparation and their use as pharmaceuticals | |
| US5658933A (en) | Substituted heterocyclic carboxamide esters, their preparation and their use as pharmaceuticals | |
| EP0650961B1 (fr) | Amides d'acide carboxylique hétérocycliques substitués, leur preparation et leur utilisation comme médicaments | |
| CA2251647C (fr) | Derives de substitution d'isoquinoline-3-carboxamides; leur preparation et leur emploi comme produits pharmaceutiques | |
| KR20000065090A (ko) | 3-알콕시피리딘-2-카복실산아미드에스테르,이의제조방법및약제로서의이의용도 | |
| DE19536263A1 (de) | Substituierte Chinolin-2-carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel | |
| DE4433928A1 (de) | Substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel | |
| DE4434288A1 (de) | Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel | |
| DE4337271A1 (de) | Substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel | |
| DE4337270A1 (de) | Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel | |
| MXPA98008644A (en) | Amques of substitute isoquinolin-3-carboxylic acid, its preparation and its employment as a medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| MM9K | Patent not in force due to non-payment of renewal fees |