CA1132607A - Mercaptoacylamidobenzoyl glycine and mucolytic process - Google Patents
Mercaptoacylamidobenzoyl glycine and mucolytic processInfo
- Publication number
- CA1132607A CA1132607A CA301,723A CA301723A CA1132607A CA 1132607 A CA1132607 A CA 1132607A CA 301723 A CA301723 A CA 301723A CA 1132607 A CA1132607 A CA 1132607A
- Authority
- CA
- Canada
- Prior art keywords
- glycine
- benzoyl
- mercaptoacetylamino
- salt
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 29
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 title abstract description 42
- 239000004471 Glycine Substances 0.000 title abstract description 25
- 230000000510 mucolytic effect Effects 0.000 title abstract description 16
- RHBAQSBIDUVBHN-UHFFFAOYSA-N 2-[[3-[(2-sulfanylacetyl)amino]benzoyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(NC(=O)CS)=C1 RHBAQSBIDUVBHN-UHFFFAOYSA-N 0.000 claims abstract description 16
- -1 amine salts Chemical class 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 2
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- SDERRUCPVJNARU-UHFFFAOYSA-N methyl 2-[[3-(3-oxobutanethioylamino)benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC(NC(=S)CC(C)=O)=C1 SDERRUCPVJNARU-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- AJGDJNRXDGNBHC-UHFFFAOYSA-M sodium;2-[[3-[(2-sulfanylacetyl)amino]benzoyl]amino]acetate Chemical compound [Na+].[O-]C(=O)CNC(=O)C1=CC=CC(NC(=O)CS)=C1 AJGDJNRXDGNBHC-UHFFFAOYSA-M 0.000 claims 2
- GPUVVPRYZCFJOS-UHFFFAOYSA-N 2-(2-hydroxyethylamino)ethanol;2-[[3-[(2-sulfanylacetyl)amino]benzoyl]amino]acetic acid Chemical compound OCCNCCO.OC(=O)CNC(=O)C1=CC=CC(NC(=O)CS)=C1 GPUVVPRYZCFJOS-UHFFFAOYSA-N 0.000 claims 1
- YBPYKDKPGPUSLJ-UHFFFAOYSA-N ethanamine;2-[[3-[(2-sulfanylacetyl)amino]benzoyl]amino]acetic acid Chemical compound CCN.OC(=O)CNC(=O)C1=CC=CC(NC(=O)CS)=C1 YBPYKDKPGPUSLJ-UHFFFAOYSA-N 0.000 claims 1
- SZCRWTONZMFENT-UHFFFAOYSA-M potassium;2-[[3-[(2-sulfanylacetyl)amino]benzoyl]amino]acetate Chemical compound [K+].[O-]C(=O)CNC(=O)C1=CC=CC(NC(=O)CS)=C1 SZCRWTONZMFENT-UHFFFAOYSA-M 0.000 claims 1
- 239000003172 expectorant agent Substances 0.000 abstract description 9
- 229940066491 mucolytics Drugs 0.000 abstract description 9
- 229910052783 alkali metal Inorganic materials 0.000 abstract description 3
- 150000001340 alkali metals Chemical class 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 210000003097 mucus Anatomy 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 9
- 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 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 125000003396 thiol group Chemical group [H]S* 0.000 description 8
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- WUWHFEHKUQVYLF-UHFFFAOYSA-M sodium;2-aminoacetate Chemical compound [Na+].NCC([O-])=O WUWHFEHKUQVYLF-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 5
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 5
- 206010036790 Productive cough Diseases 0.000 description 5
- 239000001110 calcium chloride Substances 0.000 description 5
- 229910001628 calcium chloride Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 210000003802 sputum Anatomy 0.000 description 5
- 208000024794 sputum Diseases 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 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 3
- YNNJBBFQUFWGBX-UHFFFAOYSA-N 3-[(2-chloroacetyl)amino]benzoyl chloride Chemical compound ClCC(=O)NC1=CC=CC(C(Cl)=O)=C1 YNNJBBFQUFWGBX-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- FDIWRLNJDKKDHB-UHFFFAOYSA-N azanium;2-aminoacetate Chemical compound [NH4+].NCC([O-])=O FDIWRLNJDKKDHB-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- OSQPUMRCKZAIOZ-UHFFFAOYSA-N carbon dioxide;ethanol Chemical compound CCO.O=C=O OSQPUMRCKZAIOZ-UHFFFAOYSA-N 0.000 description 3
- 150000002169 ethanolamines Chemical class 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- UDZHNOUYXZRNPF-UHFFFAOYSA-N 3-[(2-chloroacetyl)amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC(=O)CCl)=C1 UDZHNOUYXZRNPF-UHFFFAOYSA-N 0.000 description 2
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- VYQLXFDWYFQLHL-UHFFFAOYSA-M potassium;2-thiophen-2-ylacetate Chemical compound [K+].[O-]C(=O)CC1=CC=CS1 VYQLXFDWYFQLHL-UHFFFAOYSA-M 0.000 description 2
- 230000036515 potency Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 150000007970 thio esters Chemical class 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- FQJRGYQBPLXCJF-UHFFFAOYSA-N 2-sulfanyl-1-[4-(2-sulfanylacetyl)piperazin-1-yl]ethanone Chemical class SCC(=O)N1CCN(C(=O)CS)CC1 FQJRGYQBPLXCJF-UHFFFAOYSA-N 0.000 description 1
- CFCZEUSSNNHZOJ-UHFFFAOYSA-N 3-[(2-sulfanylacetyl)amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC(=O)CS)=C1 CFCZEUSSNNHZOJ-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- CYMJZPZNYDPMBK-UHFFFAOYSA-N azanium;2-[[3-[(2-sulfanylacetyl)amino]benzoyl]amino]acetate Chemical compound N.OC(=O)CNC(=O)C1=CC=CC(NC(=O)CS)=C1 CYMJZPZNYDPMBK-UHFFFAOYSA-N 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003866 digestant Substances 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000003434 inspiratory effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- GZWNUORNEQHOAW-UHFFFAOYSA-M potassium;2-aminoacetate Chemical compound [K+].NCC([O-])=O GZWNUORNEQHOAW-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003139 primary aliphatic amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000005619 secondary aliphatic amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- CXLGQBARPPVJBZ-UHFFFAOYSA-M sodium;2-[[3-[(2-sulfanylacetyl)amino]benzoyl]amino]acetate;hydrate Chemical compound O.[Na+].[O-]C(=O)CNC(=O)C1=CC=CC(NC(=O)CS)=C1 CXLGQBARPPVJBZ-UHFFFAOYSA-M 0.000 description 1
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical class O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 150000004763 sulfides Chemical class 0.000 description 1
- 150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/806,877 US4093739A (en) | 1977-06-15 | 1977-06-15 | Mercaptoacylamidobenzoyl glycine and mucolytic process |
| US806,877 | 1977-06-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1132607A true CA1132607A (en) | 1982-09-28 |
Family
ID=25195031
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA301,723A Expired CA1132607A (en) | 1977-06-15 | 1978-04-21 | Mercaptoacylamidobenzoyl glycine and mucolytic process |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US4093739A (enExample) |
| JP (1) | JPS545933A (enExample) |
| AU (1) | AU520094B2 (enExample) |
| BE (1) | BE868114A (enExample) |
| CA (1) | CA1132607A (enExample) |
| CH (1) | CH635067A5 (enExample) |
| DE (1) | DE2825931C2 (enExample) |
| DK (1) | DK268478A (enExample) |
| ES (1) | ES470825A1 (enExample) |
| FI (1) | FI71307C (enExample) |
| FR (1) | FR2394526A1 (enExample) |
| GB (1) | GB2001958B (enExample) |
| GR (1) | GR73530B (enExample) |
| IE (1) | IE46995B1 (enExample) |
| IT (1) | IT1107483B (enExample) |
| LU (1) | LU79805A1 (enExample) |
| NL (1) | NL7806360A (enExample) |
| PH (1) | PH13512A (enExample) |
| SE (1) | SE441526B (enExample) |
| YU (1) | YU40195B (enExample) |
| ZA (1) | ZA783443B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5296500A (en) * | 1991-08-30 | 1994-03-22 | The Procter & Gamble Company | Use of N-acetyl-cysteine and derivatives for regulating skin wrinkles and/or skin atrophy |
| SE9103572D0 (sv) * | 1991-11-29 | 1991-11-29 | Astra Ab | Organic salts of n,n'-diacetyl cystine |
| EP0655461B1 (en) * | 1993-11-16 | 2000-06-07 | Novartis AG | Cyclic amino acid derivatives having ACE and NEP inhibiting activity |
| US5432186A (en) * | 1993-11-16 | 1995-07-11 | Ciba-Geigy Corporation | Cyclic amino acid derivatives |
| US5451405A (en) * | 1994-04-25 | 1995-09-19 | Chesebrough-Pond's Usa Co. | Skin treatment composition |
| JP3261969B2 (ja) * | 1996-02-29 | 2002-03-04 | 豊田合成株式会社 | ホースとその製造方法 |
| US6294695B1 (en) | 1998-03-26 | 2001-09-25 | Mount Sinai School Of Medicine Of The City University Of New York | Aminobenzoic acid derivatives having anti-tumorigenic activity methods of making and using the same |
| JP2003106051A (ja) * | 2001-09-28 | 2003-04-09 | Tostem Corp | サッシ |
| US6797319B2 (en) * | 2002-05-31 | 2004-09-28 | Kimberly-Clark Worldwide, Inc. | Application of foam to tissue products using a liquid permeable partition |
| EP3678739B1 (en) | 2017-09-07 | 2024-03-13 | The Children's Hospital of Philadelphia | Compositions and methods for treatment of hereditary cystatin c amyloid angiopathy ( hccaa) and other neurodegenerative disorders associated with aberrant amyloid deposits |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2520293A (en) * | 1947-01-30 | 1950-08-29 | Endo Products Inc | Mercaptoacetanilide derivatives |
| US3091569A (en) * | 1960-08-26 | 1963-05-28 | Mead Johnson & Co | Mucolytic-nu-acylated sulfhydryl compositions and process for treating animal mucus |
| US3663690A (en) * | 1969-08-12 | 1972-05-16 | Hoechst Co American | Mucolytic composition and method of treatment of broncho-pulmonary disorders therewith |
| BE789811A (fr) * | 1971-10-07 | 1973-04-06 | Bristol Myers Co | 1,4-bis-acylpiperazines |
| BE789838A (fr) * | 1971-10-13 | 1973-02-01 | Cerm Cent Europ Rech Mauvernay | Nouveaux derives de la cysteine et leur application en therapeutique |
| FR2187327B1 (enExample) * | 1972-06-15 | 1975-06-20 | Rech Pharm Scientifiques | |
| US3971828A (en) * | 1972-10-03 | 1976-07-27 | Santen Pharmaceutical Co. Ltd. | N-(mercaptoacyl)aminoacids |
| US3857951A (en) * | 1973-09-14 | 1974-12-31 | Cassenne Lab Sa | Use of 2-mercaptopropionylglycine and its alkali metal salts in treating respiratory diseases |
| US4005222A (en) * | 1975-05-21 | 1977-01-25 | Mead Johnson & Company | Mucolytic mercaptoacylamidobenzoic and benzenesulfonic acid compounds and process |
-
1977
- 1977-06-15 US US05/806,877 patent/US4093739A/en not_active Expired - Lifetime
-
1978
- 1978-03-24 US US05/889,674 patent/US4132803A/en not_active Expired - Lifetime
- 1978-04-21 CA CA301,723A patent/CA1132607A/en not_active Expired
- 1978-06-09 YU YU1375/78A patent/YU40195B/xx unknown
- 1978-06-10 GR GR56494A patent/GR73530B/el unknown
- 1978-06-12 FI FI781866A patent/FI71307C/fi not_active IP Right Cessation
- 1978-06-12 NL NL7806360A patent/NL7806360A/xx not_active Application Discontinuation
- 1978-06-13 JP JP7046078A patent/JPS545933A/ja active Granted
- 1978-06-13 LU LU79805A patent/LU79805A1/xx unknown
- 1978-06-14 AU AU37112/78A patent/AU520094B2/en not_active Expired
- 1978-06-14 SE SE7806880A patent/SE441526B/sv not_active IP Right Cessation
- 1978-06-14 FR FR7817799A patent/FR2394526A1/fr active Granted
- 1978-06-14 BE BE188564A patent/BE868114A/xx not_active IP Right Cessation
- 1978-06-14 IT IT49864/78A patent/IT1107483B/it active
- 1978-06-14 DE DE2825931A patent/DE2825931C2/de not_active Expired
- 1978-06-14 IE IE1194/78A patent/IE46995B1/en unknown
- 1978-06-14 DK DK268478A patent/DK268478A/da not_active Application Discontinuation
- 1978-06-14 GB GB7826928A patent/GB2001958B/en not_active Expired
- 1978-06-15 ZA ZA00783443A patent/ZA783443B/xx unknown
- 1978-06-15 ES ES470825A patent/ES470825A1/es not_active Expired
- 1978-06-15 CH CH655278A patent/CH635067A5/de not_active IP Right Cessation
- 1978-06-19 PH PH21281A patent/PH13512A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6225657B2 (enExample) | 1987-06-04 |
| IE46995B1 (en) | 1983-11-30 |
| DK268478A (da) | 1978-12-16 |
| IT7849864A0 (it) | 1978-06-14 |
| ZA783443B (en) | 1979-06-27 |
| FR2394526A1 (fr) | 1979-01-12 |
| GB2001958B (en) | 1982-02-03 |
| AU3711278A (en) | 1979-12-20 |
| LU79805A1 (fr) | 1979-02-02 |
| GB2001958A (en) | 1979-02-14 |
| JPS545933A (en) | 1979-01-17 |
| SE7806880L (sv) | 1978-12-16 |
| IE781194L (en) | 1978-12-15 |
| US4132803A (en) | 1979-01-02 |
| FI781866A7 (fi) | 1978-12-16 |
| IT1107483B (it) | 1985-11-25 |
| SE441526B (sv) | 1985-10-14 |
| AU520094B2 (en) | 1982-01-14 |
| US4093739A (en) | 1978-06-06 |
| FR2394526B1 (enExample) | 1980-07-04 |
| ES470825A1 (es) | 1979-10-01 |
| DE2825931C2 (de) | 1987-01-29 |
| PH13512A (en) | 1980-06-03 |
| BE868114A (fr) | 1978-12-14 |
| YU137578A (en) | 1983-01-21 |
| NL7806360A (nl) | 1978-12-19 |
| GR73530B (enExample) | 1984-03-12 |
| YU40195B (en) | 1985-08-31 |
| CH635067A5 (de) | 1983-03-15 |
| DE2825931A1 (de) | 1979-01-04 |
| FI71307C (fi) | 1986-12-19 |
| FI71307B (fi) | 1986-09-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |