IL108962A - Use of hydroxybenzyl substituted sulfur containing heterocyclic derivatives a process for their preparation and pharmaceutical compositions containing them - Google Patents

Use of hydroxybenzyl substituted sulfur containing heterocyclic derivatives a process for their preparation and pharmaceutical compositions containing them

Info

Publication number: IL108962A
Authority: IL; Israel
Prior art keywords: alkyl; hydrogen; compound; methyl; thiazolidinone
Prior art date: 1989-12-21

Application number

IL10896290A

Other languages

English (en)

Hebrew (he)

Original Assignee

Lilly Co Eli

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1989-12-21

Filing date

1990-12-13

Publication date

1996-12-05

1990-12-13 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1996-12-05 Publication of IL108962A publication Critical patent/IL108962A/en

Links

238000000034 method Methods 0.000 title abstract description 51
230000008569 process Effects 0.000 title abstract description 13
238000002360 preparation method Methods 0.000 title description 32
229910052717 sulfur Inorganic materials 0.000 title description 2
239000011593 sulfur Substances 0.000 title description 2
239000004215 Carbon black (E152) Substances 0.000 title 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title 1
125000000623 heterocyclic group Chemical group 0.000 title 1
229930195733 hydrocarbon Natural products 0.000 title 1
150000002430 hydrocarbons Chemical class 0.000 title 1
239000000825 pharmaceutical preparation Substances 0.000 title 1
KIWUVOGUEXMXSV-UHFFFAOYSA-N rhodanine Chemical class O=C1CSC(=S)N1 KIWUVOGUEXMXSV-UHFFFAOYSA-N 0.000 abstract description 18
208000022559 Inflammatory bowel disease Diseases 0.000 abstract description 11
241000124008 Mammalia Species 0.000 abstract description 6
239000008194 pharmaceutical composition Substances 0.000 abstract description 6
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract description 2
150000001875 compounds Chemical class 0.000 description 161
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
239000000243 solution Substances 0.000 description 75
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
239000001257 hydrogen Substances 0.000 description 65
229910052739 hydrogen Inorganic materials 0.000 description 65
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
-1 HYDROXYBENZYL Chemical group 0.000 description 51
239000000203 mixture Substances 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
125000000217 alkyl group Chemical group 0.000 description 34
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 31
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 description 30
238000004458 analytical method Methods 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
125000004435 hydrogen atom Chemical group [H]* 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 22
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 20
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
239000010410 layer Substances 0.000 description 20
238000010992 reflux Methods 0.000 description 20
239000010936 titanium Substances 0.000 description 20
239000000047 product Substances 0.000 description 19
229910052719 titanium Inorganic materials 0.000 description 19
239000002904 solvent Substances 0.000 description 18
229960001701 chloroform Drugs 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
229920002472 Starch Polymers 0.000 description 15
239000004480 active ingredient Substances 0.000 description 15
150000002431 hydrogen Chemical group 0.000 description 15
235000019698 starch Nutrition 0.000 description 15
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000008107 starch Substances 0.000 description 14
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 13
125000003545 alkoxy group Chemical group 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
239000007787 solid Substances 0.000 description 13
229940095064 tartrate Drugs 0.000 description 13
238000012360 testing method Methods 0.000 description 13
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
238000010828 elution Methods 0.000 description 12
239000003446 ligand Substances 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 12
235000011152 sodium sulphate Nutrition 0.000 description 12
235000019359 magnesium stearate Nutrition 0.000 description 11
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 11
238000010898 silica gel chromatography Methods 0.000 description 11
DOZRDZLFLOODMB-UHFFFAOYSA-N 3,5-di-tert-Butyl-4-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC(C=O)=CC(C(C)(C)C)=C1O DOZRDZLFLOODMB-UHFFFAOYSA-N 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
238000010438 heat treatment Methods 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
239000000758 substrate Substances 0.000 description 10
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 9
229940126062 Compound A Drugs 0.000 description 9
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 9
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 9
125000004093 cyano group Chemical group *C#N 0.000 description 9
239000007788 liquid Substances 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
239000007858 starting material Substances 0.000 description 9
238000003756 stirring Methods 0.000 description 9
239000003826 tablet Substances 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
241001061127 Thione Species 0.000 description 8
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
239000003814 drug Substances 0.000 description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 7
238000001914 filtration Methods 0.000 description 7
239000007903 gelatin capsule Substances 0.000 description 7
239000001632 sodium acetate Substances 0.000 description 7
235000017281 sodium acetate Nutrition 0.000 description 7
239000000725 suspension Substances 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
238000010626 work up procedure Methods 0.000 description 7
LDQZOWGKFAPUCJ-UHFFFAOYSA-N 5-[[4-hydroxy-3,5-bis(prop-2-enyl)phenyl]methyl]-1,3-thiazolidin-4-one Chemical compound C1=C(CC=C)C(O)=C(CC=C)C=C1CC1C(=O)NCS1 LDQZOWGKFAPUCJ-UHFFFAOYSA-N 0.000 description 6
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
206010061218 Inflammation Diseases 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
235000010980 cellulose Nutrition 0.000 description 6
229920002678 cellulose Polymers 0.000 description 6
239000001913 cellulose Substances 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
230000004054 inflammatory process Effects 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
239000012071 phase Substances 0.000 description 6
150000003839 salts Chemical class 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 6
239000003981 vehicle Substances 0.000 description 6
229910052727 yttrium Inorganic materials 0.000 description 6
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 5
ILMMRHUILQOQGP-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CC2C(NCS2)=O)=C1 ILMMRHUILQOQGP-UHFFFAOYSA-N 0.000 description 5
229920000168 Microcrystalline cellulose Polymers 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000002775 capsule Substances 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000005457 ice water Substances 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
239000004615 ingredient Substances 0.000 description 5
235000019813 microcrystalline cellulose Nutrition 0.000 description 5
239000008108 microcrystalline cellulose Substances 0.000 description 5
229940016286 microcrystalline cellulose Drugs 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
239000001267 polyvinylpyrrolidone Substances 0.000 description 5
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
239000011369 resultant mixture Substances 0.000 description 5
150000003462 sulfoxides Chemical class 0.000 description 5
239000000829 suppository Substances 0.000 description 5
239000000454 talc Substances 0.000 description 5
229910052623 talc Inorganic materials 0.000 description 5
235000012222 talc Nutrition 0.000 description 5
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 5
125000003831 tetrazolyl group Chemical group 0.000 description 5
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 5
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
DCJUJQMIXDDBFR-UHFFFAOYSA-N 5-[[4-hydroxy-3,5-bis(prop-2-enyl)phenyl]methylidene]-1,3-thiazolidin-4-one Chemical compound C1=C(CC=C)C(O)=C(CC=C)C=C1C=C1C(=O)NCS1 DCJUJQMIXDDBFR-UHFFFAOYSA-N 0.000 description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical compound CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 4
210000001072 colon Anatomy 0.000 description 4
238000009833 condensation Methods 0.000 description 4
230000005494 condensation Effects 0.000 description 4
XEBCWEDRGPSHQH-UHFFFAOYSA-N diisopropyl tartrate Chemical compound CC(C)OC(=O)C(O)C(O)C(=O)OC(C)C XEBCWEDRGPSHQH-UHFFFAOYSA-N 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
XNMQEEKYCVKGBD-UHFFFAOYSA-N dimethylacetylene Natural products CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000008187 granular material Substances 0.000 description 4
230000003902 lesion Effects 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
230000001590 oxidative effect Effects 0.000 description 4
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-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
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
230000009467 reduction Effects 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
230000009466 transformation Effects 0.000 description 4
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000002253 acid Substances 0.000 description 3
QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 3
239000000969 carrier Substances 0.000 description 3
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 3
229940106681 chloroacetic acid Drugs 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 3
JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
238000002156 mixing Methods 0.000 description 3
125000002757 morpholinyl group Chemical group 0.000 description 3
125000004193 piperazinyl group Chemical group 0.000 description 3
125000003386 piperidinyl group Chemical group 0.000 description 3
239000000843 powder Substances 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
241000894007 species Species 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
238000001665 trituration Methods 0.000 description 3
238000005303 weighing Methods 0.000 description 3
VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 2
NKTDTMONXHODTI-UHFFFAOYSA-N 2-pentyne Chemical compound CCC#CC NKTDTMONXHODTI-UHFFFAOYSA-N 0.000 description 2
WJQOZHYUIDYNHM-UHFFFAOYSA-N 2-tert-Butylphenol Chemical compound CC(C)(C)C1=CC=CC=C1O WJQOZHYUIDYNHM-UHFFFAOYSA-N 0.000 description 2
QKYRYMYVJBFZGG-UHFFFAOYSA-N 3-(dimethylamino)-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound CN(C)N1C(=O)CSC1=S QKYRYMYVJBFZGG-UHFFFAOYSA-N 0.000 description 2
ZBUUHLDYMKTVLT-UHFFFAOYSA-N 3-amino-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound NN1C(=O)CSC1=S ZBUUHLDYMKTVLT-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
GFFXGNKATQVCIR-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-1-oxo-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CC2S(CNC2=O)=O)=C1 GFFXGNKATQVCIR-UHFFFAOYSA-N 0.000 description 2
NKDHVZVNBMVYKJ-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-3-(methylamino)-1,3-thiazolidin-4-one Chemical compound O=C1N(NC)CSC1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NKDHVZVNBMVYKJ-UHFFFAOYSA-N 0.000 description 2
DOBNIACBFAMOPJ-UHFFFAOYSA-N 5-[(3-tert-butyl-4-hydroxy-5-methylphenyl)methylidene]-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C)=CC(C=C2C(NCS2)=O)=C1 DOBNIACBFAMOPJ-UHFFFAOYSA-N 0.000 description 2
JERYFENVDCFENH-UHFFFAOYSA-N 5-[(3-tert-butyl-4-hydroxy-5-propylphenyl)methyl]-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(CCC)=CC(CC2C(NCS2)=O)=C1 JERYFENVDCFENH-UHFFFAOYSA-N 0.000 description 2
XTHIFPMRYWMNAB-UHFFFAOYSA-N 5-[(3-tert-butyl-4-hydroxyphenyl)methyl]-1,3-thiazolidin-4-one Chemical compound C1=C(O)C(C(C)(C)C)=CC(CC2C(NCS2)=O)=C1 XTHIFPMRYWMNAB-UHFFFAOYSA-N 0.000 description 2
DJDNPBPLYRXGBJ-UHFFFAOYSA-N 5-[(4-hydroxy-3,5-dipropylphenyl)methyl]-1,3-thiazolidin-4-one Chemical compound CCCC1=C(O)C(CCC)=CC(CC2C(NCS2)=O)=C1 DJDNPBPLYRXGBJ-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 2
206010009900 Colitis ulcerative Diseases 0.000 description 2
206010012735 Diarrhoea Diseases 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
208000004232 Enteritis Diseases 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
208000025865 Ulcer Diseases 0.000 description 2
201000006704 Ulcerative Colitis Diseases 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
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 2
239000000443 aerosol Substances 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
206010009887 colitis Diseases 0.000 description 2
238000001816 cooling Methods 0.000 description 2
230000006378 damage Effects 0.000 description 2
239000008367 deionised water Substances 0.000 description 2
229910021641 deionized water Inorganic materials 0.000 description 2
LJXTYJXBORAIHX-UHFFFAOYSA-N diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1 LJXTYJXBORAIHX-UHFFFAOYSA-N 0.000 description 2
GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
238000004821 distillation Methods 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
CBOQJANXLMLOSS-UHFFFAOYSA-N ethyl vanillin Chemical compound CCOC1=CC(C=O)=CC=C1O CBOQJANXLMLOSS-UHFFFAOYSA-N 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
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 2
230000004968 inflammatory condition Effects 0.000 description 2
239000003999 initiator Substances 0.000 description 2
208000014674 injury Diseases 0.000 description 2
238000002955 isolation Methods 0.000 description 2
QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000000463 material Substances 0.000 description 2
239000002609 medium Substances 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 2
QMMOXUPEWRXHJS-UHFFFAOYSA-N pentene-2 Natural products CCC=CC QMMOXUPEWRXHJS-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
239000002243 precursor Substances 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
238000012453 sprague-dawley rat model Methods 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
125000000101 thioether group Chemical group 0.000 description 2
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 2
JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
CGHIBGNXEGJPQZ-UHFFFAOYSA-N 1-hexyne Chemical compound CCCCC#C CGHIBGNXEGJPQZ-UHFFFAOYSA-N 0.000 description 1
IBXNCJKFFQIKKY-UHFFFAOYSA-N 1-pentyne Chemical compound CCCC#C IBXNCJKFFQIKKY-UHFFFAOYSA-N 0.000 description 1
DYTUAOUIQFNOIH-UHFFFAOYSA-N 2,3-diethyl-2,3-dihydroxybutanedioic acid Chemical compound CCC(O)(C(O)=O)C(O)(CC)C(O)=O DYTUAOUIQFNOIH-UHFFFAOYSA-N 0.000 description 1
FKJBXTHQTVDIBO-UHFFFAOYSA-N 2-(3,5-ditert-butyl-4-hydroxyphenyl)-2-methyl-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C2(C)SCC(=O)N2)=C1 FKJBXTHQTVDIBO-UHFFFAOYSA-N 0.000 description 1
ICAQTXHASTZFTC-UHFFFAOYSA-N 2-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CC2SCC(=O)N2)=C1 ICAQTXHASTZFTC-UHFFFAOYSA-N 0.000 description 1
ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
229940093475 2-ethoxyethanol Drugs 0.000 description 1
AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
LAGXUTVLYNKEAR-UHFFFAOYSA-N 2-tert-butyl-6-propylphenol Chemical compound CCCC1=CC=CC(C(C)(C)C)=C1O LAGXUTVLYNKEAR-UHFFFAOYSA-N 0.000 description 1
FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 description 1
ZDMVGSGKWGGMCC-UHFFFAOYSA-N 3-(dimethylamino)-5-[[3-ethoxy-4-hydroxy-5-(3-methylthiophen-2-yl)phenyl]methylidene]-1,3-thiazolidin-4-one Chemical compound C(C)OC=1C=C(C=C(C1O)C=1SC=CC1C)C=C1C(N(CS1)N(C)C)=O ZDMVGSGKWGGMCC-UHFFFAOYSA-N 0.000 description 1
MWGLQTGMAZEKEK-UHFFFAOYSA-N 3-acetyl-5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one Chemical compound O=C1N(C(=O)C)CSC1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 MWGLQTGMAZEKEK-UHFFFAOYSA-N 0.000 description 1
USVUHCSRHRDBJJ-UHFFFAOYSA-N 3-amino-5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C=C2C(N(N)C(=S)S2)=O)=C1 USVUHCSRHRDBJJ-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
XOOFPMUHCUKCLX-UHFFFAOYSA-N 3-ethoxy-5-[(4-hydroxy-3-methoxy-5-prop-2-enylphenyl)methyl]-1,3-thiazolidin-4-one Chemical compound O=C1N(OCC)CSC1CC1=CC(CC=C)=C(O)C(OC)=C1 XOOFPMUHCUKCLX-UHFFFAOYSA-N 0.000 description 1
DQQNMIPXXNPGCV-UHFFFAOYSA-N 3-hexyne Chemical compound CCC#CCC DQQNMIPXXNPGCV-UHFFFAOYSA-N 0.000 description 1
USCSRAJGJYMJFZ-UHFFFAOYSA-N 3-methyl-1-butyne Chemical compound CC(C)C#C USCSRAJGJYMJFZ-UHFFFAOYSA-N 0.000 description 1
JKLZCQWVERBDEZ-UHFFFAOYSA-N 3-methyl-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound CN1C(=O)CSC1=S JKLZCQWVERBDEZ-UHFFFAOYSA-N 0.000 description 1
IOFKLPGWURTFMD-UHFFFAOYSA-N 3-tert-butyl-4-hydroxy-5-methylbenzaldehyde Chemical compound CC1=CC(C=O)=CC(C(C)(C)C)=C1O IOFKLPGWURTFMD-UHFFFAOYSA-N 0.000 description 1
HJAWVRGJRZJTJF-UHFFFAOYSA-N 3-tert-butyl-4-hydroxy-5-propylbenzaldehyde Chemical compound CCCC1=CC(C=O)=CC(C(C)(C)C)=C1O HJAWVRGJRZJTJF-UHFFFAOYSA-N 0.000 description 1
IBZZAKITZYDOFP-UHFFFAOYSA-N 3-tert-butyl-4-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC(C=O)=CC=C1O IBZZAKITZYDOFP-UHFFFAOYSA-N 0.000 description 1
MMNDXXBXDUWNPG-UHFFFAOYSA-N 4-hydroxy-3,5-bis(prop-2-enyl)benzaldehyde Chemical compound OC1=C(CC=C)C=C(C=O)C=C1CC=C MMNDXXBXDUWNPG-UHFFFAOYSA-N 0.000 description 1
HDZJQLIQQWIJBW-UHFFFAOYSA-N 4-hydroxy-3-prop-2-enylbenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1CC=C HDZJQLIQQWIJBW-UHFFFAOYSA-N 0.000 description 1
UUGSYFSEGOEBDY-UHFFFAOYSA-N 4-prop-2-enoxy-3-prop-2-enylbenzaldehyde Chemical compound C=CCOC1=CC=C(C=O)C=C1CC=C UUGSYFSEGOEBDY-UHFFFAOYSA-N 0.000 description 1
TYNJQOJWNMZQFZ-UHFFFAOYSA-N 4-prop-2-enoxybenzaldehyde Chemical compound C=CCOC1=CC=C(C=O)C=C1 TYNJQOJWNMZQFZ-UHFFFAOYSA-N 0.000 description 1
NESVCNSGMSCUNY-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-2-hydroxyphenyl)methyl]-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=CC(CC2C(NCS2)=O)=C1O NESVCNSGMSCUNY-UHFFFAOYSA-N 0.000 description 1
PWRGVTODAPJEIP-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CC2C(NC(=S)S2)=O)=C1 PWRGVTODAPJEIP-UHFFFAOYSA-N 0.000 description 1
OWVACVFTAXCYDQ-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-3-(propylamino)-1,3-thiazolidin-4-one Chemical compound O=C1N(NCCC)CSC1CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 OWVACVFTAXCYDQ-UHFFFAOYSA-N 0.000 description 1
FBJMAPPCXZBNEX-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-3-methyl-1,3-thiazolidin-4-one Chemical compound O=C1N(C)CSC1CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FBJMAPPCXZBNEX-UHFFFAOYSA-N 0.000 description 1
WSAUGNRLHSKLRG-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]-3-methylsulfonyl-1,3-thiazolidin-4-one 5-[(4-hydroxy-3,5-dimethylphenyl)methylidene]-3-methyl-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C=1C=C(C=C(C1O)C(C)(C)C)CC1C(N(CS1)S(=O)(=O)C)=O.CC=1C=C(C=C(C1O)C)C=C1C(N(CS1)C)=O WSAUGNRLHSKLRG-UHFFFAOYSA-N 0.000 description 1
BUDGLLLMROWLOB-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C=C2C(NCS2)=O)=C1 BUDGLLLMROWLOB-UHFFFAOYSA-N 0.000 description 1
WBDPSYDYYOULLK-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C=C2C(NC(=S)S2)=O)=C1 WBDPSYDYYOULLK-UHFFFAOYSA-N 0.000 description 1
MVJPOIQSPSAPOE-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-3-(3-methoxypropyl)-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound O=C1N(CCCOC)C(=S)SC1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 MVJPOIQSPSAPOE-UHFFFAOYSA-N 0.000 description 1
DNXBQWAKVPAADQ-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-3-(dimethylamino)-1,3-thiazolidin-4-one Chemical compound O=C1N(N(C)C)CSC1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 DNXBQWAKVPAADQ-UHFFFAOYSA-N 0.000 description 1
NDQCTXHVNPCUJS-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-3-[methyl(prop-2-enyl)amino]-1,3-thiazolidin-4-one Chemical compound O=C1N(N(CC=C)C)CSC1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NDQCTXHVNPCUJS-UHFFFAOYSA-N 0.000 description 1
IXCMEASJCGKKQS-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-3-methyl-1,3-thiazolidin-4-one Chemical compound O=C1N(C)CSC1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 IXCMEASJCGKKQS-UHFFFAOYSA-N 0.000 description 1
VFRLHWWGOKMACK-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-3-methyl-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound O=C1N(C)C(=S)SC1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 VFRLHWWGOKMACK-UHFFFAOYSA-N 0.000 description 1
NJPFWWFJOUSYKF-UHFFFAOYSA-N 5-[(3-tert-butyl-4-hydroxy-5-prop-2-enylphenyl)methylidene]-3-cyclohexyl-1,3-thiazolidin-4-one Chemical compound C=CCC1=C(O)C(C(C)(C)C)=CC(C=C2C(N(C3CCCCC3)CS2)=O)=C1 NJPFWWFJOUSYKF-UHFFFAOYSA-N 0.000 description 1
XGRBVINFGLLHEW-UHFFFAOYSA-N 5-[(3-tert-butyl-4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one Chemical compound C1=C(O)C(C(C)(C)C)=CC(C=C2C(NCS2)=O)=C1 XGRBVINFGLLHEW-UHFFFAOYSA-N 0.000 description 1
VGVHGOYVDXJLKH-UHFFFAOYSA-N 5-[[3,5-bis(ethenyl)-4-hydroxyphenyl]methylidene]-3-(3-methoxypropyl)-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound O=C1N(CCCOC)C(=S)SC1=CC1=CC(C=C)=C(O)C(C=C)=C1 VGVHGOYVDXJLKH-UHFFFAOYSA-N 0.000 description 1
KOKZVJPEWLMDKA-UHFFFAOYSA-N 5-[[4-hydroxy-3,5-bis(prop-2-enyl)phenyl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound C1=C(CC=C)C(O)=C(CC=C)C=C1C=C1C(=O)NC(=S)S1 KOKZVJPEWLMDKA-UHFFFAOYSA-N 0.000 description 1
LZEWMMJEJBYUOM-UHFFFAOYSA-N 5-[[4-hydroxy-3,5-bis(prop-2-enyl)phenyl]methylidene]-3-methyl-1,3-thiazolidin-4-one Chemical compound O=C1N(C)CSC1=CC1=CC(CC=C)=C(O)C(CC=C)=C1 LZEWMMJEJBYUOM-UHFFFAOYSA-N 0.000 description 1
GMOBYNQQGUUWTE-UHFFFAOYSA-N 5-[[4-hydroxy-3,5-di(propan-2-yl)phenyl]methyl]-1,3-thiazolidin-4-one Chemical compound CC(C)C1=C(O)C(C(C)C)=CC(CC2C(NCS2)=O)=C1 GMOBYNQQGUUWTE-UHFFFAOYSA-N 0.000 description 1
BANYQDXNBZGFAL-UHFFFAOYSA-N 5-[[4-hydroxy-3,5-di(propan-2-yl)phenyl]methyl]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound CC(C)C1=C(O)C(C(C)C)=CC(CC2C(NC(=S)S2)=O)=C1 BANYQDXNBZGFAL-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
UNELBGVHMPBWOH-UHFFFAOYSA-N C(C)C1=C(SC=C1)C1=C(C=C(C(=C1)O)C)C=C1C(NC(S1)=S)=O Chemical compound C(C)C1=C(SC=C1)C1=C(C=C(C(=C1)O)C)C=C1C(NC(S1)=S)=O UNELBGVHMPBWOH-UHFFFAOYSA-N 0.000 description 1
CISSMKTTZMCKDJ-UHFFFAOYSA-N CC(C)(C)C=1C=C(C=C(C1O)C(C)(C)C)CC1C(NC(S1)=S)=O.CC(C)(C)C=1C=C(C=C(C1O)C(C)(C)C)CC1C(NCS1)=O Chemical compound CC(C)(C)C=1C=C(C=C(C1O)C(C)(C)C)CC1C(NC(S1)=S)=O.CC(C)(C)C=1C=C(C=C(C1O)C(C)(C)C)CC1C(NCS1)=O CISSMKTTZMCKDJ-UHFFFAOYSA-N 0.000 description 1
NJWYVQDSGDKDLT-UHFFFAOYSA-N CC(CC)C=1C=C(C=C(C1O)C(CC)C)CC1C(N(CS1)C)=O.OC1=C(C=C(C=C1CCC)C=C1C(N(CS1)CCN(C)C)=O)CCC Chemical compound CC(CC)C=1C=C(C=C(C1O)C(CC)C)CC1C(N(CS1)C)=O.OC1=C(C=C(C=C1CCC)C=C1C(N(CS1)CCN(C)C)=O)CCC NJWYVQDSGDKDLT-UHFFFAOYSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
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 1
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 1
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 1
201000004624 Dermatitis Diseases 0.000 description 1
241000792859 Enema Species 0.000 description 1
238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 1
238000005727 Friedel-Crafts reaction Methods 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
206010023232 Joint swelling Diseases 0.000 description 1
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 1
206010023799 Large intestinal ulcer Diseases 0.000 description 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
206010036774 Proctitis Diseases 0.000 description 1
206010036783 Proctitis ulcerative Diseases 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
206010038063 Rectal haemorrhage Diseases 0.000 description 1
SOWVXFFKAOXIDG-UHFFFAOYSA-N S1C=CC(C)=C1C=1C=C(O)C(OCC)=CC=1C=C1SCN(N(C)C)C1=O Chemical compound S1C=CC(C)=C1C=1C=C(O)C(OCC)=CC=1C=C1SCN(N(C)C)C1=O SOWVXFFKAOXIDG-UHFFFAOYSA-N 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
208000006011 Stroke Diseases 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
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000011149 active material Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
230000004596 appetite loss Effects 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
230000008993 bowel inflammation Effects 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000000378 calcium silicate Substances 0.000 description 1
229910052918 calcium silicate Inorganic materials 0.000 description 1
229960003340 calcium silicate Drugs 0.000 description 1
235000012241 calcium silicate Nutrition 0.000 description 1
OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
229960002303 citric acid monohydrate Drugs 0.000 description 1
208000008609 collagenous colitis Diseases 0.000 description 1
230000009849 deactivation Effects 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
YSAVZVORKRDODB-WDSKDSINSA-N diethyl tartrate Chemical compound CCOC(=O)[C@@H](O)[C@H](O)C(=O)OCC YSAVZVORKRDODB-WDSKDSINSA-N 0.000 description 1
210000002249 digestive system Anatomy 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
239000012990 dithiocarbamate Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940095399 enema Drugs 0.000 description 1
208000010227 enterocolitis Diseases 0.000 description 1
230000003628 erosive effect Effects 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
229940014259 gelatin Drugs 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
MELUCTCJOARQQG-UHFFFAOYSA-N hex-2-yne Chemical compound CCCC#CC MELUCTCJOARQQG-UHFFFAOYSA-N 0.000 description 1
239000004312 hexamethylene tetramine Substances 0.000 description 1
235000010299 hexamethylene tetramine Nutrition 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000002429 hydrazines Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
150000002432 hydroperoxides Chemical class 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
230000028709 inflammatory response Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 1
208000002551 irritable bowel syndrome Diseases 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
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
ZUBZATZOEPUUQF-UHFFFAOYSA-N isopropylhexane Natural products CCCCCCC(C)C ZUBZATZOEPUUQF-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
235000021266 loss of appetite Nutrition 0.000 description 1
208000019017 loss of appetite Diseases 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
XXCMGYNVDSOFHV-UHFFFAOYSA-N n-(benzylideneamino)methanamine Chemical compound CNN=CC1=CC=CC=C1 XXCMGYNVDSOFHV-UHFFFAOYSA-N 0.000 description 1
JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
239000006187 pill Substances 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
230000000063 preceeding effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
ZTILHLWDFSMCLZ-UHFFFAOYSA-N prop-2-enylhydrazine Chemical compound NNCC=C ZTILHLWDFSMCLZ-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
239000012264 purified product Substances 0.000 description 1
239000008213 purified water Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
230000005855 radiation Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 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
QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000009528 severe injury Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012058 sterile packaged powder Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003463 sulfur Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
150000003899 tartaric acid esters Chemical class 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
KJLXVAPBVMFHOL-UHFFFAOYSA-N thiolane-2,4-dione Chemical class O=C1CSC(=O)C1 KJLXVAPBVMFHOL-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
238000000844 transformation Methods 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/14—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/36—Sulfur atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Thiazole And Isothizaole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Surgical Instruments (AREA)
Nonmetallic Welding Materials (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Magnetic Resonance Imaging Apparatus (AREA)
Eye Examination Apparatus (AREA)

IL10896290A 1989-12-21 1990-12-13 Use of hydroxybenzyl substituted sulfur containing heterocyclic derivatives a process for their preparation and pharmaceutical compositions containing them IL108962A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US45420389A	1989-12-21	1989-12-21
IL9665490A IL96654A (en)	1989-12-21	1990-12-13	Hydroxybenzyl substituted sulfur containing heterocyclic derivatives their preparation and pharmaceutical compositions containing them

Publications (1)

Publication Number	Publication Date
IL108962A true IL108962A (en)	1996-12-05

Family

ID=23803709

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
IL10896290A IL108962A (en)	1989-12-21	1990-12-13	Use of hydroxybenzyl substituted sulfur containing heterocyclic derivatives a process for their preparation and pharmaceutical compositions containing them
IL9665490A IL96654A (en)	1989-12-21	1990-12-13	Hydroxybenzyl substituted sulfur containing heterocyclic derivatives their preparation and pharmaceutical compositions containing them
IL10896294A IL108962A0 (en)	1989-12-21	1994-03-14	Use of hydroxybenzyl substituted sulfur containing heterocyclic derivatives, a process for their preparation and pharmaceutical compositions containing them

Family Applications After (2)

Application Number	Title	Priority Date	Filing Date
IL9665490A IL96654A (en)	1989-12-21	1990-12-13	Hydroxybenzyl substituted sulfur containing heterocyclic derivatives their preparation and pharmaceutical compositions containing them
IL10896294A IL108962A0 (en)	1989-12-21	1994-03-14	Use of hydroxybenzyl substituted sulfur containing heterocyclic derivatives, a process for their preparation and pharmaceutical compositions containing them

Country Status (22)

Country	Link
EP (1)	EP0434394B1 (es)
JP (1)	JP3036853B2 (es)
KR (1)	KR0176243B1 (es)
CN (1)	CN1029846C (es)
AT (1)	ATE169294T1 (es)
AU (1)	AU639734B2 (es)
CA (1)	CA2032330C (es)
CY (1)	CY2100B1 (es)
DE (1)	DE69032537T2 (es)
DK (1)	DK0434394T3 (es)
ES (1)	ES2121748T3 (es)
FI (2)	FI104251B1 (es)
HU (1)	HU216732B (es)
IE (1)	IE904633A1 (es)
IL (3)	IL108962A (es)
MX (1)	MX23803A (es)
NO (1)	NO300458B1 (es)
NZ (1)	NZ236472A (es)
PT (1)	PT96198B (es)
RU (2)	RU2036915C1 (es)
YU (1)	YU240690A (es)
ZA (1)	ZA9010041B (es)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
LU87339A1 (fr) *	1988-09-20	1990-04-06	Oreal	Nouveaux derives de benzylidene-cyclanones,leur procede de preparation,leur utilisation en tant qu'agents anti-oxydants et comme filtres solaires,compositions cosmetiques et pharmaceutiques les contenant
US5143928A (en) *	1990-03-27	1992-09-01	Warner-Lambert Company	3,5-di-tertiarybutyl-4-hydroxyphenylmethylene derivatives of 2-substituted thiazolidinones, oxazolidinones, and imidazolidinones as antiinflammatory agents
IL106877A (en) *	1992-09-10	1998-03-10	Lilly Co Eli	Rodinin derivatives for use as drugs for the treatment of Alzheimer's disease
DE69301894T2 (de) *	1992-10-28	1996-11-07	Shionogi & Co	Benzylidenderivate
US6251928B1 (en)	1994-03-16	2001-06-26	Eli Lilly And Company	Treatment of alzheimer's disease employing inhibitors of cathepsin D
US5563277A (en) *	1994-12-21	1996-10-08	Eli Lilly And Company	Process for preparing benzyl-substituted rhodanine derivatives
ES2153081T3 (es) *	1995-09-07	2001-02-16	Lilly Co Eli	Forma cristalina alternativa de tazofelona((+,-)-5-((3,5-bis(1,1-dimetiletil)-4-hidroxifenil)metil)-4-tiazolidinona).
ATE193284T1 (de) *	1995-09-07	2000-06-15	Lilly Co Eli	Verfahren zur herstellung von benzylsubstituierten rhodaninederivaten
EP0779282A1 (en) *	1995-12-14	1997-06-18	Eli Lilly And Company	Thiomorpholinone compounds for treating multiple sclerosis
US5981523A (en) *	1996-02-05	1999-11-09	Eli Lilly And Company	Compounds and methods for treating multiple sclerosis
US6063799A (en) *	1996-09-03	2000-05-16	Eli Lilly And Company	Alternate crystal form of Tazofelone
US6005142A (en)	1996-09-03	1999-12-21	Eli Lilly And Company	Process for preparing benzyl-substituted rhodanine derivatives
WO2000018748A1 (en) *	1998-09-30	2000-04-06	Roche Diagnostics Gmbh	Rhodanine derivatives for the treatment and prevention of metabolic bone disorders
WO2000018746A1 (en) *	1998-09-30	2000-04-06	Roche Diagnostics Gmbh	Thiazolidine derivatives for the treatment and prevention of metabolic bone disorders
WO2000018747A1 (en) *	1998-09-30	2000-04-06	Roche Diagnostics Gmbh	Rhodanine carboxylic acid derivatives for the treatment and prevention of metabolic bone disorders
BR0314943A (pt) *	2002-09-30	2005-08-02	Univ California	Inibidores da proteìna reguladora da condutância transmembrana da fibrose cìstica e usos destes
US7235573B2 (en)	2002-09-30	2007-06-26	The Regents Of The University Of California	Methods of treating secretory diarrhea using cystic fibrosis transmembrane conductance regulator protein inhibitors
AU2002953533A0 (en) *	2002-12-24	2003-01-16	Arthron Limited	Fc receptor modulating compounds and compositions
JP5778755B2 (ja) *	2010-04-15	2015-09-16	メルクパテントゲゼルシャフトミットベシュレンクテルハフツングＭｅｒｃｋＰａｔｅｎｔＧｅｓｅｌｌｓｃｈａｆｔｍｉｔｂｅｓｃｈｒａｅｎｋｔｅｒＨａｆｔｕｎｇ	ヒドロキノンの製造方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GR862081B (en) *	1985-08-09	1986-12-24	Lilly Co Eli	Di-t-butylphenol compounds
IE940525L (en) *	1988-05-25	1989-11-25	Warner Lambert Co	Known and selected novel arylmethylenyl derivatives of¹thiazolidinones, imidazolidinones and oxazolidinones useful¹as antiallergy agents and antiinflammatory agents
CA2013599C (en) *	1989-04-07	1999-11-16	Jill A. Panetta	Aryl-substituted rhodanine derivatives

1990
- 1990-12-13 IL IL10896290A patent/IL108962A/en not_active IP Right Cessation
- 1990-12-13 ZA ZA9010041A patent/ZA9010041B/xx unknown
- 1990-12-13 IL IL9665490A patent/IL96654A/en not_active IP Right Cessation
- 1990-12-14 NZ NZ236472A patent/NZ236472A/xx unknown
- 1990-12-14 PT PT96198A patent/PT96198B/pt active IP Right Grant
- 1990-12-14 CA CA002032330A patent/CA2032330C/en not_active Expired - Fee Related
- 1990-12-19 NO NO905478A patent/NO300458B1/no not_active IP Right Cessation
- 1990-12-19 AU AU68266/90A patent/AU639734B2/en not_active Ceased
- 1990-12-19 DE DE69032537T patent/DE69032537T2/de not_active Expired - Fee Related
- 1990-12-19 KR KR1019900021001A patent/KR0176243B1/ko not_active Expired - Fee Related
- 1990-12-19 AT AT90313923T patent/ATE169294T1/de not_active IP Right Cessation
- 1990-12-19 ES ES90313923T patent/ES2121748T3/es not_active Expired - Lifetime
- 1990-12-19 EP EP90313923A patent/EP0434394B1/en not_active Expired - Lifetime
- 1990-12-19 DK DK90313923T patent/DK0434394T3/da active
- 1990-12-19 MX MX2380390A patent/MX23803A/es unknown
- 1990-12-19 FI FI906273A patent/FI104251B1/fi not_active IP Right Cessation
- 1990-12-20 JP JP2413313A patent/JP3036853B2/ja not_active Expired - Fee Related
- 1990-12-20 CN CN90109846A patent/CN1029846C/zh not_active Expired - Fee Related
- 1990-12-20 HU HU908368A patent/HU216732B/hu not_active IP Right Cessation
- 1990-12-20 RU SU904894177A patent/RU2036915C1/ru active
- 1990-12-20 YU YU240690A patent/YU240690A/sh unknown
- 1990-12-20 IE IE463390A patent/IE904633A1/en not_active Application Discontinuation
1991
- 1991-12-24 RU SU915010352A patent/RU2050355C1/ru active
1994
- 1994-03-14 IL IL10896294A patent/IL108962A0/xx unknown
1998
- 1998-09-07 CY CY9800024A patent/CY2100B1/xx unknown
1999
- 1999-08-10 FI FI991698A patent/FI19991698L/fi unknown

Also Published As

Publication number	Publication date
FI104251B (fi)	1999-12-15
NO905478D0 (no)	1990-12-19
AU639734B2 (en)	1993-08-05
IL96654A (en)	1995-06-29
FI906273L (fi)	1991-06-22
CY2100B1 (en)	2002-04-05
HU908368D0 (en)	1991-07-29
ZA9010041B (en)	1992-08-26
IL108962A0 (en)	1994-06-24
FI19991698L (fi)	1999-08-10
EP0434394B1 (en)	1998-08-05
CN1052668A (zh)	1991-07-03
KR910011812A (ko)	1991-08-07
NO300458B1 (no)	1997-06-02
PT96198A (pt)	1991-09-30
IE904633A1 (en)	1991-07-17
FI906273A0 (fi)	1990-12-19
MX23803A (es)	1994-02-28
CA2032330C (en)	2001-05-08
EP0434394A3 (en)	1992-01-08
HUT59915A (en)	1992-07-28
CN1029846C (zh)	1995-09-27
AU6826690A (en)	1991-06-27
FI104251B1 (fi)	1999-12-15
JPH04279573A (ja)	1992-10-05
EP0434394A2 (en)	1991-06-26
DE69032537T2 (de)	1999-01-21
RU2050355C1 (ru)	1995-12-20
DE69032537D1 (de)	1998-09-10
HU216732B (hu)	1999-08-30
ES2121748T3 (es)	1998-12-16
DK0434394T3 (da)	1998-12-14
PT96198B (pt)	1998-05-29
RU2036915C1 (ru)	1995-06-09
YU240690A (sh)	1992-12-21
CA2032330A1 (en)	1991-06-22
KR0176243B1 (ko)	1999-03-20
NO905478L (no)	1991-06-24
ATE169294T1 (de)	1998-08-15
NZ236472A (en)	1993-03-26
JP3036853B2 (ja)	2000-04-24

Publication	Publication Date	Title
EP0434394B1 (en)	1998-08-05	Compounds for treating inflammatory bowel disease
US5387690A (en)	1995-02-07	Method of treating inflammatory bowel disease
CA1304371C (en)	1992-06-30	Benzoxazole derivatives and preparation thereof
CZ397598A3 (cs)	1999-03-17	Derivát 5-fenoxyalkyl-2,4-thiazolidindionu, způsob jeho přípravy, meziprodukty pro jeho přípravu a farmaceutický prostředek, který ho obsahuje
AU629322B2 (en)	1992-10-01	Aryl-substituted rhodanine derivatives
AU651865B2 (en)	1994-08-04	Method of treating type I diabetes
KR960012206B1 (ko)	1996-09-16	티아졸리딘-2,4-디온 유도체 및 이의 염, 이의 제조방법 및 이의 용도
US5731336A (en)	1998-03-24	Method for treating multiple sclerosis
CH633010A5 (fr)	1982-11-15	Derives de l'isoquinoleine, leur preparation et medicament qui les contient.
JPH05222017A (ja)	1993-08-31	チアジアジノン類
US5563277A (en)	1996-10-08	Process for preparing benzyl-substituted rhodanine derivatives
US4312869A (en)	1982-01-26	Monosubstituted piperazines
FR2576900A1 (fr)	1986-08-08	Derives de cyclohepto-imidazole 2-substitue, agents anti-ulcereux et procede pour leur preparation
US5468761A (en)	1995-11-21	4-methyl-5-substituted-1,3-oxazoles having anti-inflammatory activity
JPH0440356B2 (es)	1992-07-02
US4910216A (en)	1990-03-20	2-(3,5-dimethyl-4-hydroxyphenyl)indole derivatives
KR20050007056A (ko)	2005-01-17	5-리폭시게나제 억제용 약학적 조성물
JPH0469385A (ja)	1992-03-04	新規イミダゾリン誘導体

Legal Events

Date	Code	Title
1997-06-10	FF	Patent granted
1997-09-30	KB	Patent renewed
2001-06-14	RH	Patent void
2005-09-25	MM9K	Patent not in force due to non-payment of renewal fees