IL92028A

IL92028A - History of 4-pyridyl-1,3-dioxane-5-ile-alkanoic acid, processes for their preparation and pharmaceutical preparations containing them

History of 4-pyridyl-1,3-dioxane-5-ile-alkanoic acid, processes for their preparation and pharmaceutical preparations containing them

Info

Publication number: IL92028A
Authority: IL; Israel
Prior art keywords: formula; methyl; alkyl; hydroxy; ethyl
Prior art date: 1988-10-21

Application number

IL9202889A

Other languages

English (en)

Hebrew (he)

Other versions

IL92028A0 (en

Original Assignee

Zeneca Ltd

Priority date

1988-10-21

Filing date

1989-10-17

Publication date

1994-06-24

1988-10-21 Priority claimed from GB888824667A external-priority patent/GB8824667D0/en

1988-10-21 Priority claimed from GB888824668A external-priority patent/GB8824668D0/en

1989-08-18 Priority claimed from GB898918937A external-priority patent/GB8918937D0/en

1989-10-17 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1990-07-12 Publication of IL92028A0 publication Critical patent/IL92028A0/xx

1994-06-24 Publication of IL92028A publication Critical patent/IL92028A/en

Links

238000000034 method Methods 0.000 title claims abstract description 80
239000002253 acid Substances 0.000 title claims abstract description 49
230000008569 process Effects 0.000 title claims abstract description 26
-1 4-pyridyl-1,3-dioxan---5-yl Chemical group 0.000 title claims description 182
239000008194 pharmaceutical composition Substances 0.000 title abstract description 9
238000002360 preparation method Methods 0.000 title description 4
239000001257 hydrogen Substances 0.000 claims abstract description 47
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 47
125000003545 alkoxy group Chemical group 0.000 claims abstract description 46
125000001424 substituent group Chemical group 0.000 claims abstract description 43
125000002947 alkylene group Chemical group 0.000 claims abstract description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 32
150000003839 salts Chemical class 0.000 claims abstract description 32
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims abstract description 11
238000004519 manufacturing process Methods 0.000 claims abstract description 11
125000003158 alcohol group Chemical group 0.000 claims abstract description 9
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 7
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 21
150000001875 compounds Chemical class 0.000 claims description 104
125000000217 alkyl group Chemical group 0.000 claims description 73
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
NIONDZDPPYHYKY-SNAWJCMRSA-N (2E)-hexenoic acid Chemical compound CCC\C=C\C(O)=O NIONDZDPPYHYKY-SNAWJCMRSA-N 0.000 claims description 38
125000005843 halogen group Chemical group 0.000 claims description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
125000004093 cyano group Chemical group *C#N 0.000 claims description 26
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 21
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 18
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 17
239000003085 diluting agent Substances 0.000 claims description 16
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 15
239000005977 Ethylene Chemical group 0.000 claims description 15
239000002585 base Substances 0.000 claims description 15
150000007513 acids Chemical class 0.000 claims description 13
150000002148 esters Chemical class 0.000 claims description 12
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
125000001309 chloro group Chemical group Cl* 0.000 claims description 11
125000001624 naphthyl group Chemical group 0.000 claims description 11
239000007858 starting material Substances 0.000 claims description 11
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
125000001153 fluoro group Chemical group F* 0.000 claims description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
239000000126 substance Substances 0.000 claims description 9
125000001544 thienyl group Chemical group 0.000 claims description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
125000001246 bromo group Chemical group Br* 0.000 claims description 8
239000003153 chemical reaction reagent Substances 0.000 claims description 8
150000002373 hemiacetals Chemical class 0.000 claims description 8
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 7
229910052783 alkali metal Inorganic materials 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
150000002009 diols Chemical class 0.000 claims description 7
125000002541 furyl group Chemical group 0.000 claims description 7
125000004814 1,1-dimethylethylene group Chemical group [H]C([H])([H])C([*:1])(C([H])([H])[H])C([H])([H])[*:2] 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000004450 alkenylene group Chemical group 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
VQTUBCCKSQIDNK-UHFFFAOYSA-N iso-butene Natural products CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims description 6
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 5
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
125000005236 alkanoylamino group Chemical group 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
125000004414 alkyl thio group Chemical group 0.000 claims description 5
230000015572 biosynthetic process Effects 0.000 claims description 5
125000001589 carboacyl group Chemical group 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
229910052705 radium Inorganic materials 0.000 claims description 5
229910052701 rubidium Inorganic materials 0.000 claims description 5
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
150000001340 alkali metals Chemical class 0.000 claims description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
150000001768 cations Chemical class 0.000 claims description 4
125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 4
229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
239000011707 mineral Substances 0.000 claims description 4
125000005704 oxymethylene group Chemical group [H]C([H])([*:2])O[*:1] 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
229910052727 yttrium Inorganic materials 0.000 claims description 3
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 2
239000003377 acid catalyst Substances 0.000 claims description 2
125000002015 acyclic group Chemical group 0.000 claims description 2
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
150000003863 ammonium salts Chemical class 0.000 claims description 2
150000001450 anions Chemical class 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical group C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 claims description 2
125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
150000002500 ions Chemical class 0.000 claims description 2
125000006353 oxyethylene group Chemical group 0.000 claims description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 8
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 claims 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
201000010099 disease Diseases 0.000 abstract description 8
230000001225 therapeutic effect Effects 0.000 abstract description 6
125000004076 pyridyl group Chemical group 0.000 abstract description 5
125000000532 dioxanyl group Chemical group 0.000 abstract description 3
208000006673 asthma Diseases 0.000 abstract description 2
208000026106 cerebrovascular disease Diseases 0.000 abstract description 2
208000027866 inflammatory disease Diseases 0.000 abstract description 2
208000031225 myocardial ischemia Diseases 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
239000000243 solution Substances 0.000 description 90
239000000203 mixture Substances 0.000 description 85
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 84
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
239000003921 oil Substances 0.000 description 77
235000019198 oils Nutrition 0.000 description 77
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 65
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
239000007787 solid Substances 0.000 description 56
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
230000036961 partial effect Effects 0.000 description 37
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
238000012360 testing method Methods 0.000 description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
229910001868 water Inorganic materials 0.000 description 32
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
150000001299 aldehydes Chemical class 0.000 description 29
239000002904 solvent Substances 0.000 description 28
239000000284 extract Substances 0.000 description 26
DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 26
238000003818 flash chromatography Methods 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
235000011121 sodium hydroxide Nutrition 0.000 description 21
229940083608 sodium hydroxide Drugs 0.000 description 21
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
238000001704 evaporation Methods 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
239000005557 antagonist Substances 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 12
229910052786 argon Inorganic materials 0.000 description 11
ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
230000000694 effects Effects 0.000 description 10
238000004452 microanalysis Methods 0.000 description 10
230000002401 inhibitory effect Effects 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 8
241001465754 Metazoa Species 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
238000010992 reflux Methods 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
239000000443 aerosol Substances 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
206010006482 Bronchospasm Diseases 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 6
230000007885 bronchoconstriction Effects 0.000 description 6
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 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
239000000725 suspension Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
MDOCEOLOBMVLLH-UHFFFAOYSA-N 2-methyl-2-(4-methylsulfonylphenoxy)propanal Chemical compound O=CC(C)(C)OC1=CC=C(S(C)(=O)=O)C=C1 MDOCEOLOBMVLLH-UHFFFAOYSA-N 0.000 description 5
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 5
235000019270 ammonium chloride Nutrition 0.000 description 5
230000008485 antagonism Effects 0.000 description 5
210000001772 blood platelet Anatomy 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
230000009467 reduction Effects 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
238000001665 trituration Methods 0.000 description 5
RDMWPFDMKLKMJP-UHFFFAOYSA-N 2-(4-methoxyphenoxy)-2-methylpropanal Chemical compound COC1=CC=C(OC(C)(C)C=O)C=C1 RDMWPFDMKLKMJP-UHFFFAOYSA-N 0.000 description 4
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
241000282472 Canis lupus familiaris Species 0.000 description 4
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
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 4
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 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
239000004147 Sorbitan trioleate Substances 0.000 description 4
PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 4
150000001241 acetals Chemical class 0.000 description 4
239000002775 capsule Substances 0.000 description 4
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