BE565975A - - Google Patents

Info

Publication number

BE565975A

BE565975A BE565975DA BE565975A BE 565975 A BE565975 A BE 565975A BE 565975D A BE565975D A BE 565975DA BE 565975 A BE565975 A BE 565975A

Authority

BE

Belgium

Prior art keywords

fluoro

chloro

esters

derivatives

cortisone

Prior art date

Links

• Espacenet
• Global Dossier
• Discuss

• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 52
• JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 claims description 30
• 150000002148 esters Chemical class 0.000 claims description 29
• 150000001875 compounds Chemical class 0.000 claims description 20
• 239000000126 substance Substances 0.000 claims description 19
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
• DKGAVHZHDRPRBM-UHFFFAOYSA-N t-BuOH Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 238000000034 method Methods 0.000 claims description 13
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• 125000001153 fluoro group Chemical group F* 0.000 claims description 7
• 239000007858 starting material Substances 0.000 claims description 7
• 238000006356 dehydrogenation reaction Methods 0.000 claims description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
• 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims description 5
• 125000004043 oxo group Chemical group O=* 0.000 claims description 5
• 150000001805 chlorine compounds Chemical class 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 229940000207 Selenious Acid Drugs 0.000 claims description 3
• MCAHWIHFGHIESP-UHFFFAOYSA-N Selenous acid Chemical compound O[Se](O)=O MCAHWIHFGHIESP-UHFFFAOYSA-N 0.000 claims description 3
• 244000005700 microbiome Species 0.000 claims description 3
• 239000000186 progesterone Substances 0.000 claims description 3
• 241000223600 Alternaria Species 0.000 claims description 2
• 241000577959 Calonectria Species 0.000 claims description 2
• MYYIMZRZXIQBGI-HVIRSNARSA-N Fluprednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](F)C2=C1 MYYIMZRZXIQBGI-HVIRSNARSA-N 0.000 claims description 2
• 241000223218 Fusarium Species 0.000 claims description 2
• 241000427940 Fusarium solani Species 0.000 claims description 2
• 241000190509 Ophiobolus Species 0.000 claims description 2
• 241000203720 Pimelobacter simplex Species 0.000 claims description 2
• MSXVEPNJUHWQHW-UHFFFAOYSA-N Tert-Amyl alcohol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims description 2
• 150000003509 tertiary alcohols Chemical class 0.000 claims description 2
• JYGXADMDTFJGBT-VWUMJDOOSA-N Cortisol Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims 2
• 229960000890 hydrocortisone Drugs 0.000 claims 2
• BHDHELFREODRJK-XRYUJSLGSA-N (8S,9R,10S,13S,14S,17R)-9-fluoro-17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,11-dione Chemical compound O=C1CC[C@]2(C)[C@@]3(F)C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 BHDHELFREODRJK-XRYUJSLGSA-N 0.000 claims 1
• RYTFNVIZBLCIMZ-WMSSUOLPSA-N (8S,9S,10R,13S,14S,17S)-17-acetyl-16-chloro-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(Cl)[C@H](C(=O)C)[C@@]1(C)CC2 RYTFNVIZBLCIMZ-WMSSUOLPSA-N 0.000 claims 1
• MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 claims 1
• 241000555695 Didymella Species 0.000 claims 1
• 229960004544 cortisone Drugs 0.000 claims 1
• 150000007530 organic bases Chemical group 0.000 claims 1
• 150000003124 pregnadienes Chemical class 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
• CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 72
• 239000000203 mixture Substances 0.000 description 71
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
• 239000000243 solution Substances 0.000 description 47
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
• RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• 239000002244 precipitate Substances 0.000 description 22
• 239000002253 acid Substances 0.000 description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
• HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
• 239000012299 nitrogen atmosphere Substances 0.000 description 18
• PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 239000000706 filtrate Substances 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
• 239000008079 hexane Substances 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• WQDUMFSSJAZKTM-UHFFFAOYSA-N sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
• 239000000047 product Substances 0.000 description 11
• 229960000583 Acetic Acid Drugs 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 10
• 239000000284 extract Substances 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• 239000002904 solvent Substances 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• PNEYBMLMFCGWSK-UHFFFAOYSA-N AI2O3 Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 9
• 235000011054 acetic acid Nutrition 0.000 description 9
• 238000004587 chromatography analysis Methods 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
• 235000017557 sodium bicarbonate Nutrition 0.000 description 9
• 150000007513 acids Chemical class 0.000 description 8
• WGLPBDUCMAPZCE-UHFFFAOYSA-N trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 8
• 238000005406 washing Methods 0.000 description 8
• 150000008064 anhydrides Chemical class 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 239000005457 ice water Substances 0.000 description 7
• 238000002844 melting Methods 0.000 description 7
• YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
• 238000010828 elution Methods 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 125000004432 carbon atoms Chemical group C* 0.000 description 5
• 230000000875 corresponding Effects 0.000 description 5
• KRHYYFGTRYWZRS-UHFFFAOYSA-N HF Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
• 229940117975 chromium trioxide Drugs 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000005712 crystallization Effects 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• -1 heterocyclic dicarboxylic acids Chemical class 0.000 description 4
• 229960005205 prednisolone Drugs 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000012265 solid product Substances 0.000 description 4
• VUVGYHUDAICLFK-UHFFFAOYSA-N Perosmic oxide Chemical compound O=[Os](=O)(=O)=O VUVGYHUDAICLFK-UHFFFAOYSA-N 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M Potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• OIGNJSKKLXVSLS-VWUMJDOOSA-N Prednisolone Chemical class O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 3
• WYVAMUWZEOHJOQ-UHFFFAOYSA-N Propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 3
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N Valeric acid Natural products CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 3
• 230000001264 neutralization Effects 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 235000019260 propionic acid Nutrition 0.000 description 3
• 150000003343 selenium compounds Chemical class 0.000 description 3
• 239000001187 sodium carbonate Substances 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 239000003643 water by type Substances 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butanoic acid Chemical class CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• POULHZVOKOAJMA-UHFFFAOYSA-N Lauric acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
• TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N Oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• FBUKVWPVBMHYJY-UHFFFAOYSA-N Pelargonic acid Natural products CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-N Perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M Potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L Sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N Stearic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N Thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 239000003610 charcoal Substances 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
• 229960004618 prednisone Drugs 0.000 description 2
• 150000003118 prednisones Chemical class 0.000 description 2
• 150000004672 propanoic acids Chemical class 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 238000007127 saponification reaction Methods 0.000 description 2
• 229940065287 selenium compounds Drugs 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• BHTWZQKERRCPRZ-RYRKJORJSA-N (8S,13S,14S)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,17-dione Chemical class C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)(C(CC3)=O)CC3)C3=C21 BHTWZQKERRCPRZ-RYRKJORJSA-N 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• 239000005631 2,4-D Substances 0.000 description 1
• OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-Dichlorophenoxyacetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 1
• BUSOTUQRURCMCM-UHFFFAOYSA-N 3-Phenoxypropionic acid Chemical compound OC(=O)CCOC1=CC=CC=C1 BUSOTUQRURCMCM-UHFFFAOYSA-N 0.000 description 1
• HXUIDZOMTRMIOE-UHFFFAOYSA-N 3-oxo-3-phenylpropionic acid Chemical compound OC(=O)CC(=O)C1=CC=CC=C1 HXUIDZOMTRMIOE-UHFFFAOYSA-N 0.000 description 1
• SODPIMGUZLOIPE-UHFFFAOYSA-N 4-Chlorophenoxyacetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1 SODPIMGUZLOIPE-UHFFFAOYSA-N 0.000 description 1
• YKYVPFIBWVQZCE-UHFFFAOYSA-N 4-phenoxybutanoic acid Chemical compound OC(=O)CCCOC1=CC=CC=C1 YKYVPFIBWVQZCE-UHFFFAOYSA-N 0.000 description 1
• YVTQHZDUDUCGRD-UHFFFAOYSA-N 5-bromofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)O1 YVTQHZDUDUCGRD-UHFFFAOYSA-N 0.000 description 1
• UZROOFLUFHWOJQ-ADDDSGAWSA-N 6α-Fluoropregn-4-ene-3,20-dione Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 UZROOFLUFHWOJQ-ADDDSGAWSA-N 0.000 description 1
• 241000487074 Alosa alosa Species 0.000 description 1
• 244000144725 Amygdalus communis Species 0.000 description 1
• 235000011437 Amygdalus communis Nutrition 0.000 description 1
• 229940064005 Antibiotic throat preparations Drugs 0.000 description 1
• 229940083879 Antibiotics FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE Drugs 0.000 description 1
• 229940042052 Antibiotics for systemic use Drugs 0.000 description 1
• 229940042786 Antitubercular Antibiotics Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 241001273385 Boeremia lycopersici Species 0.000 description 1
• 229940041514 Candida albicans extract Drugs 0.000 description 1
• 229940064701 Corticosteroid nasal preparations for topical use Drugs 0.000 description 1
• 229960001334 Corticosteroids Drugs 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N Cypionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N Glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 229940093922 Gynecological Antibiotics Drugs 0.000 description 1
• 210000004185 Liver Anatomy 0.000 description 1
• 235000021360 Myristic acid Nutrition 0.000 description 1
• VBTQNRFWXBXZQR-UHFFFAOYSA-N N-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N Palmitic acid Natural products CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N Phenylacetic acid Natural products OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N Phenylpropanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N Pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 239000004698 Polyethylene (PE) Substances 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N Prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• RJKFOVLPORLFTN-STHVQZNPSA-N Progesterone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC(=O)CC4)CC3)CC2)CC1 RJKFOVLPORLFTN-STHVQZNPSA-N 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• 206010041277 Sodium retention Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 229940024982 Topical Antifungal Antibiotics Drugs 0.000 description 1
• FRPZMMHWLSIFAZ-UHFFFAOYSA-N Undecylenic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 230000002378 acidificating Effects 0.000 description 1
• 238000007792 addition Methods 0.000 description 1
• 238000005054 agglomeration Methods 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000006136 alcoholysis reaction Methods 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 235000020224 almond Nutrition 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 239000000538 analytical sample Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 235000013405 beer Nutrition 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 150000001559 benzoic acids Chemical class 0.000 description 1
• 230000003115 biocidal Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 235000005824 corn Nutrition 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 238000002592 echocardiography Methods 0.000 description 1
• 150000002118 epoxides Chemical class 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 230000002349 favourable Effects 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 150000002311 glutaric acids Chemical class 0.000 description 1
• 230000002394 glycogenic Effects 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 229940079866 intestinal antibiotics Drugs 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 230000002906 microbiologic Effects 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 229940005935 ophthalmologic Antibiotics Drugs 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 150000002943 palmitic acids Chemical class 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 150000003117 prednisolones Chemical class 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 229960003387 progesterone Drugs 0.000 description 1
• 150000003839 salts Chemical class 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• BUGBHKTXTAQXES-UHFFFAOYSA-N selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
• 229910052711 selenium Inorganic materials 0.000 description 1
• 239000011669 selenium Substances 0.000 description 1
• 231100000486 side effect Toxicity 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 229940001607 sodium bisulfite Drugs 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• 125000000542 sulfonic acid group Chemical group 0.000 description 1
• 230000002522 swelling Effects 0.000 description 1
• 229940083878 topical for treatment of hemorrhoids and anal fissures Corticosteroids Drugs 0.000 description 1
• 230000001131 transforming Effects 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229960002703 undecylenic acid Drugs 0.000 description 1
• 239000012138 yeast extract Substances 0.000 description 1