FR2476071A1 - Nouveaux acides 2-amino-3-(a-hydroxybenzyl)-phenylacetiques et leurs esters et amides, utiles notamment comme agents anti-inflammatoires, et compositions pharmaceutiques les contenant - Google Patents
Nouveaux acides 2-amino-3-(a-hydroxybenzyl)-phenylacetiques et leurs esters et amides, utiles notamment comme agents anti-inflammatoires, et compositions pharmaceutiques les contenant Download PDFInfo
- Publication number
- FR2476071A1 FR2476071A1 FR8103188A FR8103188A FR2476071A1 FR 2476071 A1 FR2476071 A1 FR 2476071A1 FR 8103188 A FR8103188 A FR 8103188A FR 8103188 A FR8103188 A FR 8103188A FR 2476071 A1 FR2476071 A1 FR 2476071A1
- Authority
- FR
- France
- Prior art keywords
- amino
- lower alkyl
- hydrogen
- hydroxybenzyl
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001408 amides Chemical class 0.000 title claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 229940121363 anti-inflammatory agent Drugs 0.000 title 1
- 239000002260 anti-inflammatory agent Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
- 239000004480 active ingredient Substances 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 239000001257 hydrogen Substances 0.000 claims abstract description 19
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 150000001768 cations Chemical class 0.000 claims abstract description 7
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 239000011734 sodium Substances 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 150000004677 hydrates Chemical class 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 229910014033 C-OH Inorganic materials 0.000 claims description 6
- 229910014570 C—OH Inorganic materials 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
- 229940049953 phenylacetate Drugs 0.000 claims description 6
- SULMNCIGVRMBIU-UHFFFAOYSA-N 2-[2-amino-3-[hydroxy(phenyl)methyl]phenyl]acetic acid Chemical class NC1=C(CC(O)=O)C=CC=C1C(O)C1=CC=CC=C1 SULMNCIGVRMBIU-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 5
- 229940079593 drug Drugs 0.000 claims 3
- 231100000252 nontoxic Toxicity 0.000 claims 2
- 230000003000 nontoxic effect Effects 0.000 claims 2
- 229940126601 medicinal product Drugs 0.000 claims 1
- 229960003424 phenylacetic acid Drugs 0.000 claims 1
- 239000003279 phenylacetic acid Substances 0.000 claims 1
- HZOREEUASZHZBI-UHFFFAOYSA-M sodium;2-phenylacetate Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1 HZOREEUASZHZBI-UHFFFAOYSA-M 0.000 claims 1
- 231100000167 toxic agent Toxicity 0.000 claims 1
- 239000003440 toxic substance Substances 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- -1 AMINO Chemical class 0.000 abstract description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 5
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical class F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 abstract 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 2
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical class C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 70
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- 238000002360 preparation method Methods 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 238000000921 elemental analysis Methods 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- 229910001868 water Inorganic materials 0.000 description 24
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 12
- 239000007868 Raney catalyst Substances 0.000 description 11
- 229910000564 Raney nickel Inorganic materials 0.000 description 11
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 11
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 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 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
- 229920002472 Starch Polymers 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- NRAJMXHXQHCBHO-UHFFFAOYSA-N (2-aminophenyl)-(2-fluorophenyl)methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1F NRAJMXHXQHCBHO-UHFFFAOYSA-N 0.000 description 2
- 125000006334 2,4-difluoro benzoyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(F)C([H])=C1F 0.000 description 2
- JZTNRIZCEQXHCX-UHFFFAOYSA-N 2-(2-amino-3-benzoyl-5-chlorophenyl)-n-methylacetamide Chemical compound CNC(=O)CC1=CC(Cl)=CC(C(=O)C=2C=CC=CC=2)=C1N JZTNRIZCEQXHCX-UHFFFAOYSA-N 0.000 description 2
- BNUTYMOAQFOMEB-UHFFFAOYSA-N 2-(2-amino-3-benzoyl-5-chlorophenyl)acetamide Chemical compound NC(=O)CC1=CC(Cl)=CC(C(=O)C=2C=CC=CC=2)=C1N BNUTYMOAQFOMEB-UHFFFAOYSA-N 0.000 description 2
- FPRGALQPEHLMNK-UHFFFAOYSA-N 2-(2-amino-3-benzoylphenyl)-2-methylsulfanylacetamide Chemical compound CSC(C(N)=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N FPRGALQPEHLMNK-UHFFFAOYSA-N 0.000 description 2
- CBDVPOKBVAEIMF-UHFFFAOYSA-N 2-(2-amino-3-benzoylphenyl)-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N CBDVPOKBVAEIMF-UHFFFAOYSA-N 0.000 description 2
- RKFHYQGDKLNMOQ-UHFFFAOYSA-N 2-(2-amino-3-benzoylphenyl)-n-methyl-2-methylsulfanylacetamide Chemical compound CNC(=O)C(SC)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N RKFHYQGDKLNMOQ-UHFFFAOYSA-N 0.000 description 2
- GAQARSOLIPKSCK-UHFFFAOYSA-N 2-(2-amino-3-benzoylphenyl)-n-methylacetamide Chemical compound CNC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N GAQARSOLIPKSCK-UHFFFAOYSA-N 0.000 description 2
- HSKTWHGUQYMEDV-UHFFFAOYSA-N 2-[2-amino-3-(2,4-dichlorobenzoyl)phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1N HSKTWHGUQYMEDV-UHFFFAOYSA-N 0.000 description 2
- XAARRDGAECXQPW-UHFFFAOYSA-N 2-[2-amino-3-(4-fluorobenzoyl)phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC(F)=CC=2)=C1N XAARRDGAECXQPW-UHFFFAOYSA-N 0.000 description 2
- QKICJZJTTGUDBP-UHFFFAOYSA-N 2-[3-benzoyl-2-(dimethylamino)phenyl]acetamide Chemical compound CN(C)C1=C(CC(N)=O)C=CC=C1C(=O)C1=CC=CC=C1 QKICJZJTTGUDBP-UHFFFAOYSA-N 0.000 description 2
- CJXBHFANXQMZBF-UHFFFAOYSA-N 2-phenylethanethioamide Chemical compound NC(=S)CC1=CC=CC=C1 CJXBHFANXQMZBF-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- QZNJPJDUBTYMRS-UHFFFAOYSA-M amfenac sodium hydrate Chemical compound O.[Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=CC=C1 QZNJPJDUBTYMRS-UHFFFAOYSA-M 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000003245 coal Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- XJDQUPFWVIUWNZ-UHFFFAOYSA-N o-ethyl propanethioate Chemical compound CCOC(=S)CC XJDQUPFWVIUWNZ-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- SWAULJUBWSQJIE-UHFFFAOYSA-M sodium;2-(2-amino-3-benzoyl-5-chlorophenyl)acetate Chemical compound [Na+].NC1=C(CC([O-])=O)C=C(Cl)C=C1C(=O)C1=CC=CC=C1 SWAULJUBWSQJIE-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- GRDGBWVSVMLKBV-UHFFFAOYSA-N (2-amino-5-nitrophenyl)-(2-chlorophenyl)methanone Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C(=O)C1=CC=CC=C1Cl GRDGBWVSVMLKBV-UHFFFAOYSA-N 0.000 description 1
- KIQAJJIMMVVAOZ-UHFFFAOYSA-N (2-aminophenyl)-(2,4-dichlorophenyl)methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1Cl KIQAJJIMMVVAOZ-UHFFFAOYSA-N 0.000 description 1
- LFMHZYLLULKEAM-UHFFFAOYSA-N (2-aminophenyl)-(2,4-difluorophenyl)methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=C(F)C=C1F LFMHZYLLULKEAM-UHFFFAOYSA-N 0.000 description 1
- APHLSUBLNQBFTM-UHFFFAOYSA-N (2-aminophenyl)-(4-chlorophenyl)methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1 APHLSUBLNQBFTM-UHFFFAOYSA-N 0.000 description 1
- WJDPHVJEFVAKMT-UHFFFAOYSA-N (2-aminophenyl)-[4-(trifluoromethyl)phenyl]methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=C(C(F)(F)F)C=C1 WJDPHVJEFVAKMT-UHFFFAOYSA-N 0.000 description 1
- BGHNVTURKDZXMZ-UHFFFAOYSA-N 1-morpholin-4-ylpropane-1-thione Chemical compound CCC(=S)N1CCOCC1 BGHNVTURKDZXMZ-UHFFFAOYSA-N 0.000 description 1
- DUFFXPLJIMJGDY-UHFFFAOYSA-N 2-(2-amino-3-benzoyl-5-chlorophenyl)-2-methylsulfanylacetamide Chemical compound CSC(C(N)=O)C1=CC(Cl)=CC(C(=O)C=2C=CC=CC=2)=C1N DUFFXPLJIMJGDY-UHFFFAOYSA-N 0.000 description 1
- KGMINWKBJFPMMI-UHFFFAOYSA-N 2-(2-amino-3-benzoyl-5-chlorophenyl)-2-phenylsulfanylacetamide Chemical compound C=1C(Cl)=CC(C(=O)C=2C=CC=CC=2)=C(N)C=1C(C(=O)N)SC1=CC=CC=C1 KGMINWKBJFPMMI-UHFFFAOYSA-N 0.000 description 1
- DQAGOEKCOUPTFB-UHFFFAOYSA-N 2-(2-amino-3-benzoyl-5-chlorophenyl)-n-methyl-2-methylsulfanylacetamide Chemical compound CNC(=O)C(SC)C1=CC(Cl)=CC(C(=O)C=2C=CC=CC=2)=C1N DQAGOEKCOUPTFB-UHFFFAOYSA-N 0.000 description 1
- ZDPDBTKMOHMUCZ-UHFFFAOYSA-N 2-(2-amino-3-benzoylphenyl)-1-morpholin-4-ylethanone Chemical compound C1=CC=C(C(=O)C=2C=CC=CC=2)C(N)=C1CC(=O)N1CCOCC1 ZDPDBTKMOHMUCZ-UHFFFAOYSA-N 0.000 description 1
- FKWRGEMOTJECSA-UHFFFAOYSA-N 2-(2-amino-3-benzoylphenyl)-2-methylsulfanyl-1-morpholin-4-ylethanone Chemical compound C=1C=CC(C(=O)C=2C=CC=CC=2)=C(N)C=1C(SC)C(=O)N1CCOCC1 FKWRGEMOTJECSA-UHFFFAOYSA-N 0.000 description 1
- SUMXHTAHXORDBD-UHFFFAOYSA-N 2-(2-amino-3-benzoylphenyl)-n,n-dimethyl-2-methylsulfanylacetamide Chemical compound CN(C)C(=O)C(SC)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N SUMXHTAHXORDBD-UHFFFAOYSA-N 0.000 description 1
- OVQFPFBQZUMPRJ-UHFFFAOYSA-N 2-[2-(2-amino-3-benzoylphenyl)phenyl]-1-morpholin-4-ylethanone Chemical compound NC1=C(C=CC=C1C(C1=CC=CC=C1)=O)C1=C(C=CC=C1)CC(=O)N1CCOCC1 OVQFPFBQZUMPRJ-UHFFFAOYSA-N 0.000 description 1
- CQHPOZQTVGWMBK-UHFFFAOYSA-N 2-[2-amino-3-(2,4-difluorobenzoyl)phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C(=CC(F)=CC=2)F)=C1N CQHPOZQTVGWMBK-UHFFFAOYSA-N 0.000 description 1
- QDJLJVRESHRIBY-UHFFFAOYSA-N 2-[2-amino-3-(2-fluorobenzoyl)phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C(=CC=CC=2)F)=C1N QDJLJVRESHRIBY-UHFFFAOYSA-N 0.000 description 1
- GBBWTEGVCMKKAK-UHFFFAOYSA-N 2-[2-amino-3-(4-chlorobenzoyl)phenyl]-2-phenylsulfanylacetamide Chemical compound C=1C=CC(C(=O)C=2C=CC(Cl)=CC=2)=C(N)C=1C(C(=O)N)SC1=CC=CC=C1 GBBWTEGVCMKKAK-UHFFFAOYSA-N 0.000 description 1
- QYWOBAQCODTFCM-UHFFFAOYSA-N 2-[2-amino-3-(4-chlorobenzoyl)phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC(Cl)=CC=2)=C1N QYWOBAQCODTFCM-UHFFFAOYSA-N 0.000 description 1
- PVARPHBOLNOERP-UHFFFAOYSA-N 2-[2-amino-3-(4-fluorobenzoyl)phenyl]-2-propylsulfanylacetamide Chemical compound CCCSC(C(N)=O)C1=CC=CC(C(=O)C=2C=CC(F)=CC=2)=C1N PVARPHBOLNOERP-UHFFFAOYSA-N 0.000 description 1
- XTOZOEPIYJFQOP-UHFFFAOYSA-N 2-[2-amino-3-[(4-fluorophenyl)-hydroxymethyl]phenyl]acetamide Chemical compound NC1=C(C=CC=C1C(C1=CC=C(C=C1)F)O)CC(=O)N XTOZOEPIYJFQOP-UHFFFAOYSA-N 0.000 description 1
- XSMGOKQQPWBFTE-UHFFFAOYSA-N 2-[2-amino-3-[(4-fluorophenyl)-hydroxymethyl]phenyl]acetic acid Chemical compound NC1=C(C=CC=C1C(C1=CC=C(C=C1)F)O)CC(=O)O XSMGOKQQPWBFTE-UHFFFAOYSA-N 0.000 description 1
- LPYKIKWWPFNVKP-UHFFFAOYSA-N 2-[2-amino-3-[4-(trifluoromethyl)benzoyl]phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC(=CC=2)C(F)(F)F)=C1N LPYKIKWWPFNVKP-UHFFFAOYSA-N 0.000 description 1
- IEXYNRSBHKIIJK-UHFFFAOYSA-N 2-[2-amino-3-[hydroxy(phenyl)methyl]phenyl]-N,N-dimethylacetamide Chemical compound CN(C)C(=O)CC1=C(N)C(=CC=C1)C(O)C1=CC=CC=C1 IEXYNRSBHKIIJK-UHFFFAOYSA-N 0.000 description 1
- AAAYAHLNKYKTKK-UHFFFAOYSA-N 2-[2-amino-5-chloro-3-[hydroxy(phenyl)methyl]phenyl]acetic acid Chemical compound NC1=C(C=C(C=C1C(C1=CC=CC=C1)O)Cl)CC(=O)O AAAYAHLNKYKTKK-UHFFFAOYSA-N 0.000 description 1
- HGDZGMXIXUMJKC-UHFFFAOYSA-N 2-[3-[hydroxy(phenyl)methyl]phenyl]acetic acid Chemical class OC(C1=CC=CC=C1)C=1C=C(C=CC1)CC(=O)O HGDZGMXIXUMJKC-UHFFFAOYSA-N 0.000 description 1
- ANRNFVBVFMPKIR-UHFFFAOYSA-N 2-[3-benzoyl-2-(methylamino)phenyl]-2-methylsulfanylacetamide Chemical compound CNC1=C(C(SC)C(N)=O)C=CC=C1C(=O)C1=CC=CC=C1 ANRNFVBVFMPKIR-UHFFFAOYSA-N 0.000 description 1
- QIINHZUDBRVEDD-UHFFFAOYSA-N 2-[3-benzoyl-2-(methylamino)phenyl]acetamide Chemical compound CNC1=C(CC(N)=O)C=CC=C1C(=O)C1=CC=CC=C1 QIINHZUDBRVEDD-UHFFFAOYSA-N 0.000 description 1
- KIYRSYYOVDHSPG-UHFFFAOYSA-N 2-amino-2-phenylacetamide Chemical class NC(=O)C(N)C1=CC=CC=C1 KIYRSYYOVDHSPG-UHFFFAOYSA-N 0.000 description 1
- RQOLRTWYFKYGIJ-UHFFFAOYSA-N 2-methylsulfanyl-2-phenylacetamide Chemical compound CSC(C(N)=O)C1=CC=CC=C1 RQOLRTWYFKYGIJ-UHFFFAOYSA-N 0.000 description 1
- OBENGAMZEGRSIC-UHFFFAOYSA-N 2-methylsulfanylacetamide Chemical compound CSCC(N)=O OBENGAMZEGRSIC-UHFFFAOYSA-N 0.000 description 1
- VDZLYEWXIUYNSS-UHFFFAOYSA-N 2-phenyl-2-phenylsulfanylacetamide Chemical compound C=1C=CC=CC=1C(C(=O)N)SC1=CC=CC=C1 VDZLYEWXIUYNSS-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- KBRJQEVSKVOLNR-UHFFFAOYSA-N 2-phenylsulfanylacetamide Chemical compound NC(=O)CSC1=CC=CC=C1 KBRJQEVSKVOLNR-UHFFFAOYSA-N 0.000 description 1
- NTMLLKRWCFUOAP-UHFFFAOYSA-N 3-oxo-2,3-diphenylpropanamide Chemical class C=1C=CC=CC=1C(C(=O)N)C(=O)C1=CC=CC=C1 NTMLLKRWCFUOAP-UHFFFAOYSA-N 0.000 description 1
- YVKSMFUEDUPYIF-UHFFFAOYSA-N 3-oxo-2,3-diphenylpropanoic acid Chemical class C=1C=CC=CC=1C(C(=O)O)C(=O)C1=CC=CC=C1 YVKSMFUEDUPYIF-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
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- CGSJKQHIZRWICA-UHFFFAOYSA-L O.[Na+].NC1=C(C=C(C=C1C(C1=CC=CC=C1)=O)OC)CC(=O)[O-].O.O.NC1=C(C=C(C=C1C(C1=CC=CC=C1)=O)OC)CC(=O)[O-].[Na+] Chemical compound O.[Na+].NC1=C(C=C(C=C1C(C1=CC=CC=C1)=O)OC)CC(=O)[O-].O.O.NC1=C(C=C(C=C1C(C1=CC=CC=C1)=O)OC)CC(=O)[O-].[Na+] CGSJKQHIZRWICA-UHFFFAOYSA-L 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- 241000212342 Sium Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- AGKPGIOZNCJFTQ-UHFFFAOYSA-N [2-(methylamino)phenyl]-phenylmethanone Chemical compound CNC1=CC=CC=C1C(=O)C1=CC=CC=C1 AGKPGIOZNCJFTQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- SOYCMDCMZDHQFP-UHFFFAOYSA-N amfenac Chemical class NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=CC=C1 SOYCMDCMZDHQFP-UHFFFAOYSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- QUQFTIVBFKLPCL-UHFFFAOYSA-L copper;2-amino-3-[(2-amino-2-carboxylatoethyl)disulfanyl]propanoate Chemical compound [Cu+2].[O-]C(=O)C(N)CSSCC(N)C([O-])=O QUQFTIVBFKLPCL-UHFFFAOYSA-L 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- QFCOHPBSEIRXOL-UHFFFAOYSA-N ethyl 2-[2-amino-3-(4-chlorobenzoyl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(C(=O)C=2C=CC(Cl)=CC=2)=C1N QFCOHPBSEIRXOL-UHFFFAOYSA-N 0.000 description 1
- FNENWZWNOPCZGK-UHFFFAOYSA-N ethyl 2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(C)=O FNENWZWNOPCZGK-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000004508 fractional distillation Methods 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
- 235000001727 glucose Nutrition 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- XSIAJRFXWYEOJL-UHFFFAOYSA-N methyl 2-(2-amino-3-benzoylphenyl)acetate Chemical compound COC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N XSIAJRFXWYEOJL-UHFFFAOYSA-N 0.000 description 1
- UDZFAFRZPOZZMR-UHFFFAOYSA-N methyl 2-[3-benzoyl-2-(dimethylamino)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N(C)C UDZFAFRZPOZZMR-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- LYDAHNXGYJRKLL-UHFFFAOYSA-N n,n-dimethyl-2-methylsulfanylacetamide Chemical compound CSCC(=O)N(C)C LYDAHNXGYJRKLL-UHFFFAOYSA-N 0.000 description 1
- OEXMNSOPAKOPEF-UHFFFAOYSA-N n-[4-[(4-acetamidophenyl)methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CC1=CC=C(NC(C)=O)C=C1 OEXMNSOPAKOPEF-UHFFFAOYSA-N 0.000 description 1
- RKEXPBCMGJAOLM-UHFFFAOYSA-N n-methyl-2-phenylacetamide Chemical compound CNC(=O)CC1=CC=CC=C1 RKEXPBCMGJAOLM-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- SMOPCACDYYHOPI-UHFFFAOYSA-M potassium;2-(2-amino-3-benzoylphenyl)acetate;hydrate Chemical compound O.[K+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=CC=C1 SMOPCACDYYHOPI-UHFFFAOYSA-M 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 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
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- MJAQSCHBMPGJES-UHFFFAOYSA-M sodium (2-amino-3-benzoylphenyl)acetate Chemical compound [Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=CC=C1 MJAQSCHBMPGJES-UHFFFAOYSA-M 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HHMNMLHPCDSULA-UHFFFAOYSA-M sodium;2-(2-amino-3-benzoylphenyl)acetate;dihydrate Chemical compound O.O.[Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=CC=C1 HHMNMLHPCDSULA-UHFFFAOYSA-M 0.000 description 1
- GIJJYJRCYXXNHJ-UHFFFAOYSA-M sodium;2-[2-amino-3-(4-fluorobenzoyl)phenyl]acetate Chemical compound [Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=C(F)C=C1 GIJJYJRCYXXNHJ-UHFFFAOYSA-M 0.000 description 1
- HJGDSOZCBAYTER-UHFFFAOYSA-M sodium;2-[2-amino-3-(4-methoxybenzoyl)phenyl]acetate Chemical compound [Na+].C1=CC(OC)=CC=C1C(=O)C1=CC=CC(CC([O-])=O)=C1N HJGDSOZCBAYTER-UHFFFAOYSA-M 0.000 description 1
- QFCJIDHMYDIPOP-UHFFFAOYSA-M sodium;2-[2-amino-3-[(4-chlorophenyl)-hydroxymethyl]phenyl]acetate Chemical compound [Na+].NC1=C(CC([O-])=O)C=CC=C1C(O)C1=CC=C(Cl)C=C1 QFCJIDHMYDIPOP-UHFFFAOYSA-M 0.000 description 1
- BXBUVIPNRGDTNE-UHFFFAOYSA-N sodium;hydrobromide Chemical compound [Na].Br BXBUVIPNRGDTNE-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- YSWKHCWXOYCOSF-UHFFFAOYSA-N tert-butyl chlorite Chemical compound CC(C)(C)OCl=O YSWKHCWXOYCOSF-UHFFFAOYSA-N 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
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- ZRIJLVIAXXETJL-DCKSCFFVSA-J tricalcium (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(2R,3S,4R,5R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol octadecanoate phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O ZRIJLVIAXXETJL-DCKSCFFVSA-J 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- 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)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12254480A | 1980-02-19 | 1980-02-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FR2476071A1 true FR2476071A1 (fr) | 1981-08-21 |
| FR2476071B1 FR2476071B1 (enrdf_load_stackoverflow) | 1984-05-11 |
Family
ID=22403319
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8103188A Granted FR2476071A1 (fr) | 1980-02-19 | 1981-02-18 | Nouveaux acides 2-amino-3-(a-hydroxybenzyl)-phenylacetiques et leurs esters et amides, utiles notamment comme agents anti-inflammatoires, et compositions pharmaceutiques les contenant |
Country Status (11)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2465710A1 (fr) * | 1979-09-26 | 1981-03-27 | Robins Co Inc A H | Nouveaux amino-2 benzoyl-3 phenylacetamides et leurs homologues cycliques utiles comme medicaments et compositions therapeutiques et formes pharmaceutiques les contenant |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL64724A0 (en) * | 1981-02-17 | 1982-03-31 | Robins Co Inc A H | 2-amino-3-(halobenzoyl)-methylphenylacetic acids and esters and salts thereof and pharmaceutical compositions containing them |
| US5475034A (en) * | 1994-06-06 | 1995-12-12 | Alcon Laboratories, Inc. | Topically administrable compositions containing 3-benzoylphenylacetic acid derivatives for treatment of ophthalmic inflammatory disorders |
| AR030345A1 (es) * | 2000-08-14 | 2003-08-20 | Alcon Inc | Metodo de tratamiento de desordenes relacionados con angiogenesis |
| AR030346A1 (es) | 2000-08-14 | 2003-08-20 | Alcon Inc | Metodo de tratamiento de desordenes neurodegenerativos de la retina y cabeza de nervio optico |
| US6646003B2 (en) | 2001-04-02 | 2003-11-11 | Alcon, Inc. | Method of treating ocular inflammatory and angiogenesis-related disorders of the posterior segment of the eye using an amide derivative of flurbiprofen or ketorolac |
| TWI358290B (en) | 2004-12-02 | 2012-02-21 | Alcon Inc | Topical nepafenac formulations |
| EP2389355A1 (en) * | 2009-03-12 | 2011-11-30 | Medichem, S.A. | New crystals of a benzoylbenzeneacetamide derivative |
| WO2010115906A1 (en) * | 2009-04-06 | 2010-10-14 | Medichem, S.A. | 2-{2-amino-3-[hydroxy(phenyl)methyl]phenyl} acetamide |
| CN106631881B (zh) * | 2016-09-08 | 2018-09-21 | 南京工业大学 | 2-（3-苄基-2-（二甲基氨基）苯基）乙酰胺及合成方法和用途 |
| CN112794809B (zh) * | 2019-11-14 | 2023-12-29 | 南京济群医药科技股份有限公司 | 一种高纯度奈帕芬胺中间体的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2366015A1 (fr) * | 1975-11-05 | 1978-04-28 | Robins Co Inc A H | Nouveaux acides amino-2 benzoyl-3 (5 et 6) phenylacetiques et leurs esters et sels de metaux alcalins, utiles notamment comme anti-inflammatoires, et leur procede de preparation |
| BE885393A (fr) * | 1979-09-26 | 1981-01-16 | Robins Co Inc A H | Nouveaux amino-2 benzoyl-3 phenylacetamides et leurs homologues cycliques utiles comme medicaments et compositions therapeutiques et formes pharmaceutiques les contenant |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH577461A5 (enrdf_load_stackoverflow) * | 1975-08-13 | 1976-07-15 | Robins Co Inc A H |
-
1981
- 1981-01-20 IL IL61945A patent/IL61945A/xx unknown
- 1981-02-09 IT IT67177/81A patent/IT1146744B/it active
- 1981-02-13 DE DE19813105285 patent/DE3105285A1/de not_active Withdrawn
- 1981-02-16 AU AU67330/81A patent/AU538240B2/en not_active Ceased
- 1981-02-18 CH CH1076/81A patent/CH648283A5/fr not_active IP Right Cessation
- 1981-02-18 FR FR8103188A patent/FR2476071A1/fr active Granted
- 1981-02-18 CA CA000371185A patent/CA1156655A/en not_active Expired
- 1981-02-18 NL NL8100808A patent/NL8100808A/nl not_active Application Discontinuation
- 1981-02-18 BE BE0/203830A patent/BE887566A/fr not_active IP Right Cessation
- 1981-02-18 GB GB8105091A patent/GB2071086B/en not_active Expired
- 1981-02-19 JP JP2363881A patent/JPS56131552A/ja active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2366015A1 (fr) * | 1975-11-05 | 1978-04-28 | Robins Co Inc A H | Nouveaux acides amino-2 benzoyl-3 (5 et 6) phenylacetiques et leurs esters et sels de metaux alcalins, utiles notamment comme anti-inflammatoires, et leur procede de preparation |
| BE885393A (fr) * | 1979-09-26 | 1981-01-16 | Robins Co Inc A H | Nouveaux amino-2 benzoyl-3 phenylacetamides et leurs homologues cycliques utiles comme medicaments et compositions therapeutiques et formes pharmaceutiques les contenant |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2465710A1 (fr) * | 1979-09-26 | 1981-03-27 | Robins Co Inc A H | Nouveaux amino-2 benzoyl-3 phenylacetamides et leurs homologues cycliques utiles comme medicaments et compositions therapeutiques et formes pharmaceutiques les contenant |
Also Published As
| Publication number | Publication date |
|---|---|
| CH648283A5 (fr) | 1985-03-15 |
| IL61945A0 (en) | 1981-02-27 |
| CA1156655A (en) | 1983-11-08 |
| JPS56131552A (en) | 1981-10-15 |
| NL8100808A (nl) | 1981-09-16 |
| DE3105285A1 (de) | 1982-01-21 |
| IT8167177A0 (it) | 1981-02-09 |
| IL61945A (en) | 1984-09-30 |
| GB2071086B (en) | 1984-02-08 |
| GB2071086A (en) | 1981-09-16 |
| JPH0153266B2 (enrdf_load_stackoverflow) | 1989-11-13 |
| BE887566A (fr) | 1981-06-15 |
| FR2476071B1 (enrdf_load_stackoverflow) | 1984-05-11 |
| AU538240B2 (en) | 1984-08-02 |
| AU6733081A (en) | 1981-08-27 |
| IT1146744B (it) | 1986-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS62161728A (ja) | 抗菌剤 | |
| FR2823209A1 (fr) | Nouvelles thiohydantoines et leur utilisation en therapeutique | |
| BE898278A (fr) | Benzoxazines antipsychotiques. | |
| FR2491467A1 (fr) | Nouveaux n-alkyl inferieur)-3-phenoxy-1-azetidinecarboxamides possedant notamment une activite sur le systeme nerveux central, et leur procede de preparation | |
| FR2476071A1 (fr) | Nouveaux acides 2-amino-3-(a-hydroxybenzyl)-phenylacetiques et leurs esters et amides, utiles notamment comme agents anti-inflammatoires, et compositions pharmaceutiques les contenant | |
| HU199440B (en) | Process for producing morpholine derivatives and pharmaceutical compositions comprising the compounds | |
| US4254146A (en) | 3-Benzoyl-2-nitrophenylacetic acids, metal salts, amides and esters | |
| US20110269838A1 (en) | Novel processes and pure polymorphs | |
| DE4141218A1 (de) | Thiadiazincarbonsaeureamidderivate, verfahren zu ihrer herstellung und arzneimittel | |
| CH646138A5 (fr) | Amino-2-benzoyl-3-phenylacetamides et leurs homologues cycliques utiles comme medicaments et compositions pharmaceutiques les contenant. | |
| US4233310A (en) | Antiarteriosclerotic N-(mercaptoacyl)-histidines | |
| JPS60156653A (ja) | β−フエネタノ−ルアミン誘導体 | |
| FR2499981A1 (fr) | Acides amino-2 halogenobenzoyl-3 methylphenylacetiques et leurs esters et sels utiles comme medicaments anti-inflammatoires et analgesiques | |
| EP0115714A1 (fr) | Composition pharmaceutique à action psychotrope dopanimergique | |
| FR2470770A1 (fr) | Nouveaux ethers de b-imidazolylethyle de quinoleine-2 ou 4-methanols, utiles notamment comme antimicrobiens, et leur procede de preparation | |
| FR2465733A1 (fr) | Nouveaux derives imidazolylethoxymethyliques de 1,3-dioxoloquinoleines utiles notamment comme medicaments antibacteriens et antifongiques, leur procede de preparation et compositions therapeutiques et formes pharmaceutiques les contenant | |
| CH648295A5 (fr) | Acides 2-amino-3-(alkylthiobenzyl)-phenylacetiques et leurs derives. | |
| CH645357A5 (fr) | Imino-2-imidazolidines 4-substituees utiles en therapie et des medicaments les contenant. | |
| FR2584070A1 (fr) | Nouveaux derives de l'hydroxy alkoxy 4-phenyl propyl indole, leurs sels, procede et intermediaires de preparation, application a titre de medicaments et compositions les renfermant. | |
| FR2632641A1 (fr) | ((aryl-4-piperazinyl-1)-2 ethoxy)-3 p-cymene, les derives ortho, meta, para monosubstitues ou disubstitues sur le noyau phenyle dudit produit, le procede de preparation desdits derives, et les medicaments contenant lesdits composes comme principe actif | |
| FR2504133A1 (fr) | Derives d'imidazole, leur procede de preparation et leur application therapeutique | |
| BE883665A (fr) | Nouveaux derives du benzymidazole | |
| FR2460948A1 (fr) | Nouveaux derives imidazolylethoxymethyliques du thiazole, utiles comme medicaments, leur procede de preparation et compositions therapeutiques les contenant | |
| HRP920775A2 (hr) | Novi heterociklični spojevi koji sadrže dušik i sumpor, farmaceutski preparati koji ih sadrže i postupci za dobivanje | |
| JPS5879919A (ja) | 抗炎症、鎮痛、解熱剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ST | Notification of lapse |