CY1340A - Amidines processes for their manufacture pharmaceutical preparations containing them and their use - Google Patents

Info

Publication number

CY1340A

CY1340A CY1340A CY134081A CY1340A CY 1340 A CY1340 A CY 1340A CY 1340 A CY1340 A CY 1340A CY 134081 A CY134081 A CY 134081A CY 1340 A CY1340 A CY 1340A

Authority

CY

Cyprus

Prior art keywords

formula

carbon atoms

compounds

halogen

optionally substituted

Prior art date

1980-03-04

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 48
• 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 14
• 230000008569 process Effects 0.000 title claims description 34
• 238000004519 manufacturing process Methods 0.000 title claims description 18
• 150000001409 amidines Chemical class 0.000 title abstract description 6
• -1 carboxylic acid amidines Chemical class 0.000 claims abstract description 197
• 150000003839 salts Chemical class 0.000 claims abstract description 114
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 79
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 68
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
• 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 19
• 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims abstract description 17
• 150000001875 compounds Chemical class 0.000 claims description 147
• 239000002253 acid Substances 0.000 claims description 81
• 229910052736 halogen Inorganic materials 0.000 claims description 64
• 150000002367 halogens Chemical class 0.000 claims description 62
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 53
• 125000003545 alkoxy group Chemical group 0.000 claims description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
• 125000004414 alkyl thio group Chemical group 0.000 claims description 34
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
• 229910052500 inorganic mineral Inorganic materials 0.000 claims description 29
• 239000011707 mineral Substances 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 239000007858 starting material Substances 0.000 claims description 22
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
• 238000006243 chemical reaction Methods 0.000 claims description 17
• 239000001257 hydrogen Substances 0.000 claims description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• LNDWMQWLWGXEET-UHFFFAOYSA-N 2-(1h-indol-5-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2NC=CC2=C1 LNDWMQWLWGXEET-UHFFFAOYSA-N 0.000 claims description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 125000004076 pyridyl group Chemical group 0.000 claims description 14
• 229930195733 hydrocarbon Natural products 0.000 claims description 13
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 13
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
• 238000003797 solvolysis reaction Methods 0.000 claims description 12
• 125000002947 alkylene group Chemical group 0.000 claims description 11
• 230000003647 oxidation Effects 0.000 claims description 11
• 238000007254 oxidation reaction Methods 0.000 claims description 11
• 125000001544 thienyl group Chemical group 0.000 claims description 11
• 150000002148 esters Chemical class 0.000 claims description 10
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 239000005864 Sulphur Substances 0.000 claims description 6
• 239000000543 intermediate Substances 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000001931 aliphatic group Chemical group 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
• 239000004215 Carbon black (E152) Substances 0.000 claims description 4
• 241001465754 Metazoa Species 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 4
• 230000015572 biosynthetic process Effects 0.000 claims description 4
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
• 239000005977 Ethylene Substances 0.000 claims description 3
• 125000004450 alkenylene group Chemical group 0.000 claims description 3
• 150000001450 anions Chemical class 0.000 claims description 3
• 239000000969 carrier Substances 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 2
• 229940035676 analgesics Drugs 0.000 claims description 2
• 239000000730 antalgic agent Substances 0.000 claims description 2
• 230000001741 anti-phlogistic effect Effects 0.000 claims description 2
• VNWKTOKETHGBQD-YPZZEJLDSA-N carbane Chemical group [10CH4] VNWKTOKETHGBQD-YPZZEJLDSA-N 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• 239000000463 material Substances 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
• 125000005843 halogen group Chemical group 0.000 claims 2
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 2
• 230000001225 therapeutic effect Effects 0.000 claims 1
• 239000000126 substance Substances 0.000 abstract description 12
• 239000003814 drug Substances 0.000 abstract description 3
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical group C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 abstract description 3
• 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
• 238000002844 melting Methods 0.000 description 47
• 230000008018 melting Effects 0.000 description 47
• 150000007513 acids Chemical class 0.000 description 37
• 239000002585 base Substances 0.000 description 35
• 239000003054 catalyst Substances 0.000 description 35
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 30
• 239000003795 chemical substances by application Substances 0.000 description 30
• 235000010755 mineral Nutrition 0.000 description 28
• 239000000243 solution Substances 0.000 description 28
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
• 239000000203 mixture Substances 0.000 description 25
• 239000013543 active substance Substances 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 18
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
• 125000004043 oxo group Chemical group O=* 0.000 description 16
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 235000011167 hydrochloric acid Nutrition 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• 239000001117 sulphuric acid Substances 0.000 description 15
• 235000011149 sulphuric acid Nutrition 0.000 description 15
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
• 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 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• 229910052783 alkali metal Inorganic materials 0.000 description 14
• 229910021529 ammonia Inorganic materials 0.000 description 13
• 239000000194 fatty acid Substances 0.000 description 13
• PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 12
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
• 230000002378 acidificating effect Effects 0.000 description 12
• 238000000354 decomposition reaction Methods 0.000 description 12
• 235000014113 dietary fatty acids Nutrition 0.000 description 12
• 229930195729 fatty acid Natural products 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 11
• 239000000460 chlorine Substances 0.000 description 11
• 229910052801 chlorine Inorganic materials 0.000 description 11
• 239000013078 crystal Substances 0.000 description 11
• 239000012442 inert solvent Substances 0.000 description 11
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 11
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
• 229920002472 Starch Polymers 0.000 description 10
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 10
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 10
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 10
• 150000002430 hydrocarbons Chemical class 0.000 description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
• 229920001223 polyethylene glycol Polymers 0.000 description 10
• 239000000454 talc Substances 0.000 description 10
• 229910052623 talc Inorganic materials 0.000 description 10
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
• 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 9
• 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 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 150000001408 amides Chemical class 0.000 description 9
• 150000004820 halides Chemical class 0.000 description 9
• 239000008101 lactose Substances 0.000 description 9
• 150000003254 radicals Chemical class 0.000 description 9
• 235000019698 starch Nutrition 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
• 229960000583 acetic acid Drugs 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 239000003995 emulsifying agent Substances 0.000 description 8
• 125000004494 ethyl ester group Chemical group 0.000 description 8
• 238000001704 evaporation Methods 0.000 description 8
• 230000008020 evaporation Effects 0.000 description 8
• 239000011261 inert gas Substances 0.000 description 8
• 229940093932 potassium hydroxide Drugs 0.000 description 8
• 235000011118 potassium hydroxide Nutrition 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• 125000003396 thiol group Chemical class [H]S* 0.000 description 8
• 239000002202 Polyethylene glycol Substances 0.000 description 7
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 7
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 7
• BXWNKGSJHAJOGX-UHFFFAOYSA-N n-hexadecyl alcohol Natural products CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 229910052708 sodium Inorganic materials 0.000 description 7
• 239000008107 starch Substances 0.000 description 7
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 230000010933 acylation Effects 0.000 description 6
• 238000005917 acylation reaction Methods 0.000 description 6
• 150000001340 alkali metals Chemical class 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 150000008064 anhydrides Chemical class 0.000 description 6
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
• 229910052731 fluorine Inorganic materials 0.000 description 6
• 239000011737 fluorine Substances 0.000 description 6
• 229920000159 gelatin Polymers 0.000 description 6
• 235000019322 gelatine Nutrition 0.000 description 6
• 235000011187 glycerol Nutrition 0.000 description 6
• 239000003701 inert diluent Substances 0.000 description 6
• 235000019359 magnesium stearate Nutrition 0.000 description 6
• 235000011007 phosphoric acid Nutrition 0.000 description 6
• 238000001953 recrystallisation Methods 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 125000000464 thioxo group Chemical group S=* 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 5
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 239000000654 additive Substances 0.000 description 5
• 150000003973 alkyl amines Chemical class 0.000 description 5
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 230000032050 esterification Effects 0.000 description 5
• 238000005886 esterification reaction Methods 0.000 description 5
• 150000002191 fatty alcohols Chemical class 0.000 description 5
• 239000008187 granular material Substances 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
• LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 5
• 238000005984 hydrogenation reaction Methods 0.000 description 5
• 239000005457 ice water Substances 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 229910052751 metal Inorganic materials 0.000 description 5
• 239000002184 metal Substances 0.000 description 5
• 150000007522 mineralic acids Chemical class 0.000 description 5
• 150000002825 nitriles Chemical class 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 239000002674 ointment Substances 0.000 description 5
• 239000007800 oxidant agent Substances 0.000 description 5
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 5
• 229910052698 phosphorus Inorganic materials 0.000 description 5
• 239000011574 phosphorus Substances 0.000 description 5
• 239000011591 potassium Substances 0.000 description 5
• 229910052700 potassium Inorganic materials 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 235000011121 sodium hydroxide Nutrition 0.000 description 5
• 239000000600 sorbitol Substances 0.000 description 5
• 235000010356 sorbitol Nutrition 0.000 description 5
• BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 5
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• 239000005662 Paraffin oil Substances 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 235000021355 Stearic acid Nutrition 0.000 description 4
• 125000004849 alkoxymethyl group Chemical group 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• 150000001735 carboxylic acids Chemical class 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 229960000541 cetyl alcohol Drugs 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• 239000006071 cream Substances 0.000 description 4
• 125000004093 cyano group Chemical group *C#N 0.000 description 4
• 150000002170 ethers Chemical class 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 229940014259 gelatin Drugs 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 150000008282 halocarbons Chemical class 0.000 description 4
• 150000004678 hydrides Chemical class 0.000 description 4
• SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
• 235000019198 oils Nutrition 0.000 description 4
• 125000001477 organic nitrogen group Chemical group 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
• 239000008117 stearic acid Substances 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 229940099259 vaseline Drugs 0.000 description 4
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 239000004166 Lanolin Substances 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
• 206010030113 Oedema Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 3
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 150000008378 aryl ethers Chemical class 0.000 description 3
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 3
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
• 238000009835 boiling Methods 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 3
• 239000000920 calcium hydroxide Substances 0.000 description 3
• 229910001861 calcium hydroxide Inorganic materials 0.000 description 3
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000000470 constituent Substances 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 150000004665 fatty acids Chemical class 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 125000001072 heteroaryl group Chemical group 0.000 description 3
• 150000003840 hydrochlorides Chemical class 0.000 description 3
• 238000007327 hydrogenolysis reaction Methods 0.000 description 3
• 238000011065 in-situ storage Methods 0.000 description 3
• 239000003617 indole-3-acetic acid Substances 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• 229910044991 metal oxide Inorganic materials 0.000 description 3
• 150000004706 metal oxides Chemical class 0.000 description 3
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 238000010899 nucleation Methods 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 239000012188 paraffin wax Substances 0.000 description 3
• 150000003003 phosphines Chemical class 0.000 description 3
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 3
• VBQCHPIMZGQLAZ-UHFFFAOYSA-N phosphorane Chemical class [PH5] VBQCHPIMZGQLAZ-UHFFFAOYSA-N 0.000 description 3
• 229940068917 polyethylene glycols Drugs 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 235000013772 propylene glycol Nutrition 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 150000005846 sugar alcohols Polymers 0.000 description 3
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
• 150000003512 tertiary amines Chemical class 0.000 description 3
• 229910000314 transition metal oxide Inorganic materials 0.000 description 3
• 150000003626 triacylglycerols Chemical class 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• 150000003751 zinc Chemical class 0.000 description 3
• AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
• VSUCYSQFYQEKSD-UHFFFAOYSA-N 2-(1-phenyl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetonitrile Chemical compound N12C3=CC=CC=C3C(CC#N)=C2CCN=C1C1=CC=CC=C1 VSUCYSQFYQEKSD-UHFFFAOYSA-N 0.000 description 2
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
• YXPZXWYLYBRNGQ-UHFFFAOYSA-N 2-[2-[2-(dibenzylamino)ethyl]-1h-indol-3-yl]acetamide Chemical compound N1C2=CC=CC=C2C(CC(=O)N)=C1CCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 YXPZXWYLYBRNGQ-UHFFFAOYSA-N 0.000 description 2
• OGHULTKOHFRQTL-UHFFFAOYSA-N 2-[7-fluoro-1-(4-methylsulfanylphenyl)-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetic acid Chemical compound C1=CC(SC)=CC=C1C1=NCCC2=C(CC(O)=O)C3=CC(F)=CC=C3N12 OGHULTKOHFRQTL-UHFFFAOYSA-N 0.000 description 2
• HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 239000001828 Gelatine Substances 0.000 description 2
• 239000004471 Glycine Substances 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 239000002841 Lewis acid Substances 0.000 description 2
• LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 208000025747 Rheumatic disease Diseases 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
• 150000008065 acid anhydrides Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 238000006136 alcoholysis reaction Methods 0.000 description 2
• 150000001335 aliphatic alkanes Chemical class 0.000 description 2
• 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
• 229910000272 alkali metal oxide Inorganic materials 0.000 description 2
• 150000001336 alkenes Chemical class 0.000 description 2
• 235000012211 aluminium silicate Nutrition 0.000 description 2
• 238000007098 aminolysis reaction Methods 0.000 description 2
• 238000005915 ammonolysis reaction Methods 0.000 description 2
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 2
• 150000001540 azides Chemical class 0.000 description 2
• TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• 230000001055 chewing effect Effects 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 238000006356 dehydrogenation reaction Methods 0.000 description 2
• 150000001991 dicarboxylic acids Chemical class 0.000 description 2
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
• WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000010685 fatty oil Substances 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 210000004051 gastric juice Anatomy 0.000 description 2
• 150000002334 glycols Chemical class 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 230000003301 hydrolyzing effect Effects 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 238000006317 isomerization reaction Methods 0.000 description 2
• 229940074928 isopropyl myristate Drugs 0.000 description 2
• 235000019388 lanolin Nutrition 0.000 description 2
• 150000007517 lewis acids Chemical class 0.000 description 2
• OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 description 2
• 239000011733 molybdenum Substances 0.000 description 2
• MKAYFDJUJRKDDS-UHFFFAOYSA-N n-[2-[3-(2-amino-2-oxoethyl)-1h-indol-2-yl]ethyl]benzamide Chemical compound N1C2=CC=CC=C2C(CC(=O)N)=C1CCNC(=O)C1=CC=CC=C1 MKAYFDJUJRKDDS-UHFFFAOYSA-N 0.000 description 2
• GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N n-hexadecanoic acid Natural products CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 239000012038 nucleophile Substances 0.000 description 2
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 150000003015 phosphoric acid halides Chemical class 0.000 description 2
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
• 229910052697 platinum Inorganic materials 0.000 description 2
• 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
• 229920000136 polysorbate Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• 125000001453 quaternary ammonium group Chemical group 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 230000000552 rheumatic effect Effects 0.000 description 2
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 150000003335 secondary amines Chemical class 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 125000001424 substituent group Chemical group 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 2
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
• 229910021653 sulphate ion Inorganic materials 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000002511 suppository base Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• 229940100445 wheat starch Drugs 0.000 description 2
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• DKVDSNMJXDQNCD-UHFFFAOYSA-N 1h-pyrrolo[2,3-f]quinazoline Chemical compound N1=CN=CC2=C(NC=C3)C3=CC=C21 DKVDSNMJXDQNCD-UHFFFAOYSA-N 0.000 description 1
• LSHVOZHCXKYJQM-UHFFFAOYSA-N 2-(1-phenyl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetic acid Chemical compound N12C3=CC=CC=C3C(CC(=O)O)=C2CCN=C1C1=CC=CC=C1 LSHVOZHCXKYJQM-UHFFFAOYSA-N 0.000 description 1
• YURWJMPZFFHGQP-UHFFFAOYSA-N 2-(1-thiophen-2-yl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetic acid Chemical compound N12C3=CC=CC=C3C(CC(=O)O)=C2CCN=C1C1=CC=CS1 YURWJMPZFFHGQP-UHFFFAOYSA-N 0.000 description 1
• FMWYLALQQWPEAL-UHFFFAOYSA-N 2-(6,8-dimethyl-1-phenyl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetic acid Chemical compound N12C3=CC(C)=CC(C)=C3C(CC(O)=O)=C2CCN=C1C1=CC=CC=C1 FMWYLALQQWPEAL-UHFFFAOYSA-N 0.000 description 1
• ISLJVACKQMHMCD-UHFFFAOYSA-N 2-[1-(2,6-dichlorophenyl)-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetic acid Chemical compound N12C3=CC=CC=C3C(CC(=O)O)=C2CCN=C1C1=C(Cl)C=CC=C1Cl ISLJVACKQMHMCD-UHFFFAOYSA-N 0.000 description 1
• INOGMIYWLBMAJD-UHFFFAOYSA-N 2-[1-(4-chloro-3-sulfamoylphenyl)-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetamide Chemical compound N12C3=CC=CC=C3C(CC(=O)N)=C2CCN=C1C1=CC=C(Cl)C(S(N)(=O)=O)=C1 INOGMIYWLBMAJD-UHFFFAOYSA-N 0.000 description 1
• UXNMPJKXJFJYCJ-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)-7-methoxy-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetic acid Chemical compound OC(=O)CC=1C2=CC(OC)=CC=C2N2C=1CCN=C2C1=CC=C(Cl)C=C1 UXNMPJKXJFJYCJ-UHFFFAOYSA-N 0.000 description 1
• UGZIHQRDNOGSFE-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)-7-methoxy-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetic acid;hydrochloride Chemical compound Cl.OC(=O)CC=1C2=CC(OC)=CC=C2N2C=1CCN=C2C1=CC=C(Cl)C=C1 UGZIHQRDNOGSFE-UHFFFAOYSA-N 0.000 description 1
• NURJYYJGKURXPL-UHFFFAOYSA-N 2-[2-(2-aminoethyl)-1h-indol-3-yl]acetamide Chemical compound C1=CC=C2C(CC(N)=O)=C(CCN)NC2=C1 NURJYYJGKURXPL-UHFFFAOYSA-N 0.000 description 1
• QPGVMCQUXDOOHW-UHFFFAOYSA-N 2-[2-(dibenzylamino)ethyl]-5-methoxy-4-methyl-1h-indole-3-carbonitrile Chemical compound N#CC=1C2=C(C)C(OC)=CC=C2NC=1CCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 QPGVMCQUXDOOHW-UHFFFAOYSA-N 0.000 description 1
• DSNCFCXQFPXWLG-UHFFFAOYSA-N 2-[2-[2-(dibenzylamino)ethyl]-1h-indol-3-yl]acetonitrile Chemical compound N1C2=CC=CC=C2C(CC#N)=C1CCN(CC=1C=CC=CC=1)CC1=CC=CC=C1 DSNCFCXQFPXWLG-UHFFFAOYSA-N 0.000 description 1
• YDDQXQCHZIKIKA-UHFFFAOYSA-N 2-[7-fluoro-1-(4-methylsulfanylphenyl)pyrimido[1,6-a]indol-5-yl]acetic acid Chemical compound C1=CC(SC)=CC=C1C1=NC=CC2=C(CC(O)=O)C3=CC(F)=CC=C3N12 YDDQXQCHZIKIKA-UHFFFAOYSA-N 0.000 description 1
• ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• DNXUGBMARDFRGG-UHFFFAOYSA-N 3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile Chemical compound O=C1C=CC(=O)C(C#N)=C1C#N DNXUGBMARDFRGG-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical class O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N Acetylene Chemical compound C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• YBJPKOOYXZMTKK-UHFFFAOYSA-N C1=CC=NC=C1.S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 Chemical compound C1=CC=NC=C1.S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 YBJPKOOYXZMTKK-UHFFFAOYSA-N 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• 244000060011 Cocos nucifera Species 0.000 description 1
• 235000013162 Cocos nucifera Nutrition 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
• 241000790917 Dioxys <bee> Species 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical class C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• 229930195212 Fischerindole Natural products 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical class [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 239000004141 Sodium laurylsulphate Substances 0.000 description 1
• NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
• RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 241000209140 Triticum Species 0.000 description 1
• 235000021307 Triticum Nutrition 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• FGUZFFWTBWJBIL-XWVZOOPGSA-N [(1r)-1-[(2s,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)O[C@H](CO)[C@H]1OC[C@H](O)[C@H]1O FGUZFFWTBWJBIL-XWVZOOPGSA-N 0.000 description 1
• AQMHNCQZLQUNJI-UHFFFAOYSA-N [CH2]CCCCCC Chemical compound [CH2]CCCCCC AQMHNCQZLQUNJI-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 239000012445 acidic reagent Substances 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
• 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
• 150000008046 alkali metal hydrides Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000005277 alkyl imino group Chemical group 0.000 description 1
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000323 aluminium silicate Inorganic materials 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 230000000202 analgesic effect Effects 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 150000004056 anthraquinones Chemical class 0.000 description 1
• 230000002456 anti-arthritic effect Effects 0.000 description 1
• 230000003502 anti-nociceptive effect Effects 0.000 description 1
• 150000001491 aromatic compounds Chemical class 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
• 229940073608 benzyl chloride Drugs 0.000 description 1
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 235000011010 calcium phosphates Nutrition 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
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 150000001718 carbodiimides Chemical group 0.000 description 1
• 150000004651 carbonic acid esters Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• ZFTFAPZRGNKQPU-UHFFFAOYSA-L carboxylato carbonate Chemical compound [O-]C(=O)OC([O-])=O ZFTFAPZRGNKQPU-UHFFFAOYSA-L 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 235000010418 carrageenan Nutrition 0.000 description 1
• 229920001525 carrageenan Polymers 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical class [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 229940117975 chromium trioxide Drugs 0.000 description 1
• WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
• GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• 235000013681 dietary sucrose Nutrition 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
• 150000002023 dithiocarboxylic acids Chemical class 0.000 description 1
• GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 238000004945 emulsification Methods 0.000 description 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
• OQYFLTHUUWIMRS-UHFFFAOYSA-N ethyl 2-(1-phenyl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetate Chemical compound N12C3=CC=CC=C3C(CC(=O)OCC)=C2CCN=C1C1=CC=CC=C1 OQYFLTHUUWIMRS-UHFFFAOYSA-N 0.000 description 1
• JKSRFXAZGBMESG-UHFFFAOYSA-N ethyl 2-(1-phenyl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetate;hydrochloride Chemical compound Cl.N12C3=CC=CC=C3C(CC(=O)OCC)=C2CCN=C1C1=CC=CC=C1 JKSRFXAZGBMESG-UHFFFAOYSA-N 0.000 description 1
• RMQRXLLRAUMTBB-UHFFFAOYSA-N ethyl 2-(1-thiophen-2-yl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetate Chemical compound N12C3=CC=CC=C3C(CC(=O)OCC)=C2CCN=C1C1=CC=CS1 RMQRXLLRAUMTBB-UHFFFAOYSA-N 0.000 description 1
• WAEYCALIGYWLEQ-UHFFFAOYSA-N ethyl 2-(6,8-dimethyl-1-phenyl-3,4-dihydropyrimido[1,6-a]indol-5-yl)acetate Chemical compound N12C3=CC(C)=CC(C)=C3C(CC(=O)OCC)=C2CCN=C1C1=CC=CC=C1 WAEYCALIGYWLEQ-UHFFFAOYSA-N 0.000 description 1
• XHXPBQHZUSZPPU-UHFFFAOYSA-N ethyl 2-[1-(2,6-dichlorophenyl)-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetate Chemical compound N12C3=CC=CC=C3C(CC(=O)OCC)=C2CCN=C1C1=C(Cl)C=CC=C1Cl XHXPBQHZUSZPPU-UHFFFAOYSA-N 0.000 description 1
• FEQVHGXJJNGYCL-UHFFFAOYSA-N ethyl 2-[1-(4-chloro-3-sulfamoylphenyl)-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetate Chemical compound N12C3=CC=CC=C3C(CC(=O)OCC)=C2CCN=C1C1=CC=C(Cl)C(S(N)(=O)=O)=C1 FEQVHGXJJNGYCL-UHFFFAOYSA-N 0.000 description 1
• BBKIEWMIXJJXGL-UHFFFAOYSA-N ethyl 2-[1-(4-methylsulfanylphenyl)-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetate Chemical compound N12C3=CC=CC=C3C(CC(=O)OCC)=C2CCN=C1C1=CC=C(SC)C=C1 BBKIEWMIXJJXGL-UHFFFAOYSA-N 0.000 description 1
• ZXHZGHYFJNJIGX-UHFFFAOYSA-N ethyl 2-[2-(2-aminoethyl)-5-methoxy-1h-indol-3-yl]acetate Chemical compound C1=C(OC)C=C2C(CC(=O)OCC)=C(CCN)NC2=C1 ZXHZGHYFJNJIGX-UHFFFAOYSA-N 0.000 description 1
• XZGWMLJYEYHWIM-UHFFFAOYSA-N ethyl 2-[2-(2-benzamidoethyl)-1h-indol-3-yl]acetate Chemical compound N1C2=CC=CC=C2C(CC(=O)OCC)=C1CCNC(=O)C1=CC=CC=C1 XZGWMLJYEYHWIM-UHFFFAOYSA-N 0.000 description 1
• CLQAYZQPWFPEIY-UHFFFAOYSA-N ethyl 2-[2-(dibenzylamino)-5-methoxy-1h-indol-3-yl]acetate Chemical compound N1C2=CC=C(OC)C=C2C(CC(=O)OCC)=C1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 CLQAYZQPWFPEIY-UHFFFAOYSA-N 0.000 description 1
• FOHYTTAMBQDCRP-UHFFFAOYSA-N ethyl 2-[2-[2-(thiophen-2-ylamino)ethyl]-1h-indol-3-yl]acetate Chemical compound N1C2=CC=CC=C2C(CC(=O)OCC)=C1CCNC1=CC=CS1 FOHYTTAMBQDCRP-UHFFFAOYSA-N 0.000 description 1
• IHJOONISMFCLHY-UHFFFAOYSA-N ethyl 2-[2-[2-[(4-chloro-3-sulfamoylbenzoyl)amino]ethyl]-1h-indol-3-yl]acetate Chemical compound N1C2=CC=CC=C2C(CC(=O)OCC)=C1CCNC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 IHJOONISMFCLHY-UHFFFAOYSA-N 0.000 description 1
• IHGZTSGNEMUPIK-UHFFFAOYSA-N ethyl 2-[2-[2-[(4-chlorobenzoyl)amino]ethyl]-5-methoxy-1h-indol-3-yl]acetate Chemical compound N1C2=CC=C(OC)C=C2C(CC(=O)OCC)=C1CCNC(=O)C1=CC=C(Cl)C=C1 IHGZTSGNEMUPIK-UHFFFAOYSA-N 0.000 description 1
• OGLUSGQTJGSLJG-UHFFFAOYSA-N ethyl 2-[5-fluoro-2-[2-[(4-methylbenzenecarbothioyl)amino]ethyl]indol-2-yl]acetate Chemical compound C1=C2C=C(F)C=CC2=NC1(CC(=O)OCC)CCNC(=S)C1=CC=C(C)C=C1 OGLUSGQTJGSLJG-UHFFFAOYSA-N 0.000 description 1
• CINOGWNJDCFBBY-UHFFFAOYSA-N ethyl 2-[6-(2-aminoethyl)-2-benzoyl-4,5-dimethyl-1h-indol-3-yl]acetate Chemical compound N1C2=CC(CCN)=C(C)C(C)=C2C(CC(=O)OCC)=C1C(=O)C1=CC=CC=C1 CINOGWNJDCFBBY-UHFFFAOYSA-N 0.000 description 1
• DBNWUFISLGOIAO-UHFFFAOYSA-N ethyl 2-[7-fluoro-1-(4-methyl-2-sulfooxyphenyl)-3,4-dihydropyrimido[1,6-a]indol-5-yl]acetate Chemical compound N12C3=CC=C(F)C=C3C(CC(=O)OCC)=C2CCN=C1C1=CC=C(C)C=C1OS(O)(=O)=O DBNWUFISLGOIAO-UHFFFAOYSA-N 0.000 description 1
• HBACDMXALURUAF-UHFFFAOYSA-N ethyl 2-[7-fluoro-1-(4-methylsulfanylphenyl)pyrimido[1,6-a]indol-5-yl]acetate Chemical compound N=1C=CC2=C(CC(=O)OCC)C3=CC(F)=CC=C3N2C=1C1=CC=C(SC)C=C1 HBACDMXALURUAF-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 125000004970 halomethyl group Chemical group 0.000 description 1
• 125000000623 heterocyclic group Chemical group 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
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000002429 hydrazines Chemical class 0.000 description 1
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
• JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
• 239000010512 hydrogenated peanut oil Substances 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 150000002440 hydroxy compounds Chemical class 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 150000002443 hydroxylamines Chemical class 0.000 description 1
• 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
• 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 150000004966 inorganic peroxy acids Chemical class 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 239000004922 lacquer Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 229910052987 metal hydride Inorganic materials 0.000 description 1
• 150000004681 metal hydrides Chemical class 0.000 description 1
• RIFHJAODNHLCBH-UHFFFAOYSA-N methanethione Chemical group S=[CH] RIFHJAODNHLCBH-UHFFFAOYSA-N 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 229960002900 methylcellulose Drugs 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• BDRTVPCFKSUHCJ-UHFFFAOYSA-N molecular hydrogen;potassium Chemical compound [K].[H][H] BDRTVPCFKSUHCJ-UHFFFAOYSA-N 0.000 description 1
• 229910052750 molybdenum Inorganic materials 0.000 description 1
• 229910000476 molybdenum oxide Inorganic materials 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
• ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
• 229910000510 noble metal Inorganic materials 0.000 description 1
• QGLKJKCYBOYXKC-UHFFFAOYSA-N nonaoxidotritungsten Chemical compound O=[W]1(=O)O[W](=O)(=O)O[W](=O)(=O)O1 QGLKJKCYBOYXKC-UHFFFAOYSA-N 0.000 description 1
• 150000004967 organic peroxy acids Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 125000002092 orthoester group Chemical group 0.000 description 1
• 150000002905 orthoesters Chemical class 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 150000002926 oxygen Chemical class 0.000 description 1
• 125000000913 palmityl 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])C([H])([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
• 239000006072 paste Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
• KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 150000004965 peroxy acids Chemical class 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 150000003016 phosphoric acids Chemical class 0.000 description 1
• 150000003018 phosphorus compounds Chemical class 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• 239000000049 pigment Substances 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229920000137 polyphosphoric acid Polymers 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
• 229910000105 potassium hydride Inorganic materials 0.000 description 1
• BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 239000001120 potassium sulphate Substances 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940116317 potato starch Drugs 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• NCNISYUOWMIOPI-UHFFFAOYSA-N propane-1,1-dithiol Chemical class CCC(S)S NCNISYUOWMIOPI-UHFFFAOYSA-N 0.000 description 1
• ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 150000004053 quinones Chemical class 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 229910052703 rhodium Inorganic materials 0.000 description 1
• 239000010948 rhodium Substances 0.000 description 1
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 229940100486 rice starch Drugs 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• PXLIDIMHPNPGMH-UHFFFAOYSA-N sodium chromate Chemical compound [Na+].[Na+].[O-][Cr]([O-])(=O)=O PXLIDIMHPNPGMH-UHFFFAOYSA-N 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• GGHPAKFFUZUEKL-UHFFFAOYSA-M sodium;hexadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCOS([O-])(=O)=O GGHPAKFFUZUEKL-UHFFFAOYSA-M 0.000 description 1
• NWZBFJYXRGSRGD-UHFFFAOYSA-M sodium;octadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOS([O-])(=O)=O NWZBFJYXRGSRGD-UHFFFAOYSA-M 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 229940057429 sorbitan isostearate Drugs 0.000 description 1
• 229950004959 sorbitan oleate Drugs 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 125000001174 sulfone group Chemical group 0.000 description 1
• 239000004291 sulphur dioxide Substances 0.000 description 1
• 235000010269 sulphur dioxide Nutrition 0.000 description 1
• 239000010414 supernatant solution Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
• 125000005300 thiocarboxy group Chemical group C(=S)(O)* 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 150000003582 thiophosphoric acids Chemical class 0.000 description 1
• 239000010936 titanium Substances 0.000 description 1
• 229910052719 titanium Inorganic materials 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
• 229940078499 tricalcium phosphate Drugs 0.000 description 1
• 235000019731 tricalcium phosphate Nutrition 0.000 description 1
• 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• 229960004418 trolamine Drugs 0.000 description 1
• 229910001930 tungsten oxide Inorganic materials 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 229910001935 vanadium oxide Inorganic materials 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 239000011787 zinc oxide Substances 0.000 description 1