CA1105024A - Anti-inflammatory-4,5-dicyclic-2-(substituted thio) imidazoles and their corresponding sulfoxides and sulfones - Google Patents

Anti-inflammatory-4,5-dicyclic-2-(substituted thio) imidazoles and their corresponding sulfoxides and sulfones

Info

Publication number: CA1105024A
Authority: CA; Canada
Prior art keywords: thienyl; compound; prepared; pyridyl; hydrogen
Prior art date: 1977-02-09
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA296,606A

Other languages

English (en)

French (fr)

Inventor

Saul C. Cherkofsky

Thomas R. Sharpe

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

EIDP Inc

Original Assignee

EI Du Pont de Nemours and Co

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.)

1977-02-09

Filing date

1978-02-07

Publication date

1981-07-14

1978-01-05 Priority claimed from US05/865,832 external-priority patent/US4159338A/en

1978-02-07 Application filed by EI Du Pont de Nemours and Co filed Critical EI Du Pont de Nemours and Co

1981-07-14 Application granted granted Critical

1981-07-14 Publication of CA1105024A publication Critical patent/CA1105024A/en

Status Expired legal-status Critical Current

Links

125000000446 sulfanediyl group Chemical group *S* 0.000 title abstract description 5
150000003457 sulfones Chemical class 0.000 title abstract description 4
150000003462 sulfoxides Chemical class 0.000 title abstract description 4
150000002460 imidazoles Chemical class 0.000 title description 10
PEPARVGCRJOCSI-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(1,1,2,2-tetrafluoroethylsulfonyl)-5-thiophen-2-yl-1h-imidazole Chemical compound N1C(S(=O)(=O)C(F)(F)C(F)F)=NC(C=2C=CC(F)=CC=2)=C1C1=CC=CS1 PEPARVGCRJOCSI-UHFFFAOYSA-N 0.000 claims abstract 3
238000000034 method Methods 0.000 claims description 91
230000008569 process Effects 0.000 claims description 79
150000001875 compounds Chemical class 0.000 claims description 73
229910052739 hydrogen Inorganic materials 0.000 claims description 58
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 48
-1 3-pyridyl-N?oxide Chemical group 0.000 claims description 48
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 40
239000001257 hydrogen Substances 0.000 claims description 37
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 35
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
239000000460 chlorine Substances 0.000 claims description 30
229910052801 chlorine Inorganic materials 0.000 claims description 26
229910052731 fluorine Inorganic materials 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 21
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 11
239000003795 chemical substances by application Substances 0.000 claims description 11
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
229910052794 bromium Inorganic materials 0.000 claims description 7
229910052751 metal Inorganic materials 0.000 claims description 7
239000002184 metal Substances 0.000 claims description 7
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 claims description 4
239000002168 alkylating agent Substances 0.000 claims description 4
229940100198 alkylating agent Drugs 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
239000007800 oxidant agent Substances 0.000 claims description 4
YEYQRQQDUWBEIZ-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-2-(1,1,2,2-tetrafluoroethylsulfonyl)-5-thiophen-2-yl-1h-imidazole Chemical compound N1C(S(=O)(=O)C(F)(F)C(F)F)=NC(C=2C=C(Cl)C(Cl)=CC=2)=C1C1=CC=CS1 YEYQRQQDUWBEIZ-UHFFFAOYSA-N 0.000 claims description 3
150000008064 anhydrides Chemical class 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
230000001590 oxidative effect Effects 0.000 claims description 2
235000013350 formula milk Nutrition 0.000 claims 12
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 10
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 8
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 8
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 6
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 4
238000004519 manufacturing process Methods 0.000 claims 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
FMDGQCVDJMGSQH-UHFFFAOYSA-N 2-(1,1,2,2-tetrafluoroethylsulfonyl)-4,5-dithiophen-2-yl-1h-imidazole Chemical compound C=1C=CSC=1C=1NC(S(=O)(=O)C(F)(F)C(F)F)=NC=1C1=CC=CS1 FMDGQCVDJMGSQH-UHFFFAOYSA-N 0.000 claims 2
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 2
APZIHCXATJXHCW-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2-(1,1,2,2-tetrafluoroethylsulfonyl)-5-thiophen-2-yl-1h-imidazole Chemical compound C1=CC(OC)=CC=C1C1=C(C=2SC=CC=2)NC(S(=O)(=O)C(F)(F)C(F)F)=N1 APZIHCXATJXHCW-UHFFFAOYSA-N 0.000 claims 2
LOTKSXMGKSVBJW-UHFFFAOYSA-N 5-(4-methoxyphenyl)-5-thiophen-2-yl-2-(trifluoromethylsulfonyl)-1,4-dihydroimidazole Chemical compound C1=CC(OC)=CC=C1C1(C=2SC=CC=2)N=C(S(=O)(=O)C(F)(F)F)NC1 LOTKSXMGKSVBJW-UHFFFAOYSA-N 0.000 claims 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 2
229910052740 iodine Chemical group 0.000 claims 2
239000011630 iodine Chemical group 0.000 claims 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 1
206010003246 arthritis Diseases 0.000 abstract description 10
230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
201000010099 disease Diseases 0.000 abstract description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
239000000203 mixture Substances 0.000 description 34
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
239000000047 product Substances 0.000 description 21
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
229960001701 chloroform Drugs 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
229910000027 potassium carbonate Inorganic materials 0.000 description 10
235000011181 potassium carbonates Nutrition 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
238000010992 reflux Methods 0.000 description 9
239000007787 solid Substances 0.000 description 9
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
210000002683 foot Anatomy 0.000 description 8
241000700159 Rattus Species 0.000 description 7
239000003814 drug Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000002904 solvent Substances 0.000 description 6
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000011593 sulfur Substances 0.000 description 5
229910052717 sulfur Inorganic materials 0.000 description 5
239000003826 tablet Substances 0.000 description 5
BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 5
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
238000001914 filtration Methods 0.000 description 4
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 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
229910000029 sodium carbonate Inorganic materials 0.000 description 4
238000003756 stirring Methods 0.000 description 4
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 4
239000000725 suspension Substances 0.000 description 4
BTANRVKWQNVYAZ-SCSAIBSYSA-N (2R)-butan-2-ol Chemical compound CC[C@@H](C)O BTANRVKWQNVYAZ-SCSAIBSYSA-N 0.000 description 3
RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
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 3
241000699670 Mus sp. Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000000202 analgesic effect Effects 0.000 description 3
230000002917 arthritic effect Effects 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
238000001816 cooling Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
229940043279 diisopropylamine Drugs 0.000 description 3
238000001035 drying Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
210000000548 hind-foot Anatomy 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000008297 liquid dosage form Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000000126 substance Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
JQBQAYRWGWUSIC-UHFFFAOYSA-N 2-(4-fluorophenyl)-1-thiophen-2-ylethanone Chemical compound C1=CC(F)=CC=C1CC(=O)C1=CC=CS1 JQBQAYRWGWUSIC-UHFFFAOYSA-N 0.000 description 2
ZVAKZVDJIUFFFP-UHFFFAOYSA-N 2-chlorooxolane Chemical compound ClC1CCCO1 ZVAKZVDJIUFFFP-UHFFFAOYSA-N 0.000 description 2
LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
229910021590 Copper(II) bromide Inorganic materials 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 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
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229960001138 acetylsalicylic acid Drugs 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
239000000538 analytical sample Substances 0.000 description 2
230000002456 anti-arthritic effect Effects 0.000 description 2
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
229960000905 indomethacin Drugs 0.000 description 2
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
229960002216 methylparaben Drugs 0.000 description 2
VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000003182 parenteral nutrition solution Substances 0.000 description 2
229960002895 phenylbutazone Drugs 0.000 description 2
VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
238000000746 purification Methods 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
239000000523 sample Substances 0.000 description 2
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
239000007858 starting material Substances 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
229930192474 thiophene Natural products 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 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
238000010792 warming Methods 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical compound SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 description 1
IZXWCDITFDNEBY-UHFFFAOYSA-N 1-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCl)C=C1 IZXWCDITFDNEBY-UHFFFAOYSA-N 0.000 description 1
DOOBZXAXOJNMMN-UHFFFAOYSA-N 1-thiophen-2-ylimidazole Chemical compound C1=CSC(N2C=NC=C2)=C1 DOOBZXAXOJNMMN-UHFFFAOYSA-N 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
GOIWZZQXWJVDOG-UHFFFAOYSA-N 2,2,2-trifluoroethyl trichloromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(Cl)(Cl)Cl GOIWZZQXWJVDOG-UHFFFAOYSA-N 0.000 description 1
IOHCXXVLWAKZJN-UHFFFAOYSA-N 2-(1,1,2-trifluoroethylsulfanyl)-1h-imidazole Chemical class FCC(F)(F)SC1=NC=CN1 IOHCXXVLWAKZJN-UHFFFAOYSA-N 0.000 description 1
MWHBYDHNJMOVDF-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-1-thiophen-2-ylethanone Chemical compound C1=C(Cl)C(Cl)=CC=C1CC(=O)C1=CC=CS1 MWHBYDHNJMOVDF-UHFFFAOYSA-N 0.000 description 1
CSACRTDKCPIHGB-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-2-hydroxy-1-thiophen-2-ylethanone Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(O)C(=O)C1=CC=CS1 CSACRTDKCPIHGB-UHFFFAOYSA-N 0.000 description 1
ZOUPGSMSNQLUNW-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C(Cl)=C1 ZOUPGSMSNQLUNW-UHFFFAOYSA-N 0.000 description 1
QFAKETLKGUMJHH-UHFFFAOYSA-N 2-(4-chlorophenyl)-1-thiophen-2-ylethanone Chemical compound C1=CC(Cl)=CC=C1CC(=O)C1=CC=CS1 QFAKETLKGUMJHH-UHFFFAOYSA-N 0.000 description 1
LNBPTMIVDUSKBN-UHFFFAOYSA-N 2-(4-fluorophenyl)-2-hydroxy-1-thiophen-2-ylethanone Chemical compound C=1C=C(F)C=CC=1C(O)C(=O)C1=CC=CS1 LNBPTMIVDUSKBN-UHFFFAOYSA-N 0.000 description 1
MGKPFALCNDRSQD-UHFFFAOYSA-N 2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C=C1 MGKPFALCNDRSQD-UHFFFAOYSA-N 0.000 description 1
URQJGINXGUXZQL-UHFFFAOYSA-N 2-(dimethylamino)-2-thiophen-2-ylacetonitrile Chemical compound CN(C)C(C#N)C1=CC=CS1 URQJGINXGUXZQL-UHFFFAOYSA-N 0.000 description 1
WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 1
MDELWZVHTHCFLX-UHFFFAOYSA-N 2-bromo-2-(4-fluorophenyl)-1-thiophen-2-ylethanone Chemical compound C1=CC(F)=CC=C1C(Br)C(=O)C1=CC=CS1 MDELWZVHTHCFLX-UHFFFAOYSA-N 0.000 description 1
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
NIRFVHWSWXRGCZ-UHFFFAOYSA-N 3-[5-phenyl-2-(1,1,2,2-tetrafluoroethylsulfanyl)-1h-imidazol-4-yl]pyridine Chemical compound N1C(SC(F)(F)C(F)F)=NC(C=2C=CC=CC=2)=C1C1=CC=CN=C1 NIRFVHWSWXRGCZ-UHFFFAOYSA-N 0.000 description 1
CDNHLXOFELOEOL-UHFFFAOYSA-N 3-methyl-1h-benzimidazole-2-thione Chemical compound C1=CC=C2N(C)C(S)=NC2=C1 CDNHLXOFELOEOL-UHFFFAOYSA-N 0.000 description 1
JPXCIPNJJMSYDI-UHFFFAOYSA-N 4,5-bis(4-chlorophenyl)-2-methylsulfanyl-1h-imidazole Chemical compound N1C(SC)=NC(C=2C=CC(Cl)=CC=2)=C1C1=CC=C(Cl)C=C1 JPXCIPNJJMSYDI-UHFFFAOYSA-N 0.000 description 1
BADMPUNGMZZJOP-UHFFFAOYSA-N 4,5-dithiophen-2-yl-1h-imidazole Chemical compound C1=CSC(C2=C(NC=N2)C=2SC=CC=2)=C1 BADMPUNGMZZJOP-UHFFFAOYSA-N 0.000 description 1
YSLDZCQYODZSLJ-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-thiophen-2-yl-1,3-dihydroimidazole-2-thione Chemical compound N1C(S)=NC(C=2C=C(Cl)C(Cl)=CC=2)=C1C1=CC=CS1 YSLDZCQYODZSLJ-UHFFFAOYSA-N 0.000 description 1
SBPUKRVDDSUUPT-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(1,1,2,2-tetrafluoroethylsulfanyl)-5-thiophen-2-yl-1h-imidazole Chemical compound N1C(SC(F)(F)C(F)F)=NC(C=2C=CC(Cl)=CC=2)=C1C1=CC=CS1 SBPUKRVDDSUUPT-UHFFFAOYSA-N 0.000 description 1
NDQDASDYGCUQQP-UHFFFAOYSA-N 4-(4-chlorophenyl)-5-thiophen-2-yl-1,3-dihydroimidazole-2-thione Chemical compound N1C(S)=NC(C=2C=CC(Cl)=CC=2)=C1C1=CC=CS1 NDQDASDYGCUQQP-UHFFFAOYSA-N 0.000 description 1
LTPOTMQACHYUMQ-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-thiophen-2-yl-1,3-dihydroimidazole-2-thione Chemical compound C1=CC(F)=CC=C1C1=C(C=2SC=CC=2)NC(S)=N1 LTPOTMQACHYUMQ-UHFFFAOYSA-N 0.000 description 1
ZLHTTXRBURFPFT-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-thiophen-2-yl-1h-imidazole Chemical compound C1=CC(F)=CC=C1C1=C(C=2SC=CC=2)NC=N1 ZLHTTXRBURFPFT-UHFFFAOYSA-N 0.000 description 1
XNMQSJRNUAATOK-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-thiophen-2-yl-2-(trifluoromethylsulfonyl)-1h-imidazole Chemical compound C1=CC(F)=CC=C1C1=C(C=2SC=CC=2)NC(S(=O)(=O)C(F)(F)F)=N1 XNMQSJRNUAATOK-UHFFFAOYSA-N 0.000 description 1
CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 1
BGSMPYBXIPGUIA-UHFFFAOYSA-N 4-phenyl-5-pyridin-3-yl-1,3-dihydroimidazole-2-thione Chemical compound N1C(S)=NC(C=2C=CC=CC=2)=C1C1=CC=CN=C1 BGSMPYBXIPGUIA-UHFFFAOYSA-N 0.000 description 1
OQEOPQIPVXGRAT-UHFFFAOYSA-N 5-thiophen-2-yl-1h-imidazole Chemical compound C1=CSC(C=2N=CNC=2)=C1 OQEOPQIPVXGRAT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 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
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
206010053155 Epigastric discomfort Diseases 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
208000009386 Experimental Arthritis Diseases 0.000 description 1
AIKKULXCBHRFOS-UHFFFAOYSA-N Formothion Chemical compound COP(=S)(OC)SCC(=O)N(C)C=O AIKKULXCBHRFOS-UHFFFAOYSA-N 0.000 description 1
102100039401 Gap junction beta-6 protein Human genes 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
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000186359 Mycobacterium Species 0.000 description 1
241000187479 Mycobacterium tuberculosis Species 0.000 description 1
150000001204 N-oxides Chemical class 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
206010036030 Polyarthritis Diseases 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
206010037660 Pyrexia Diseases 0.000 description 1
241000219289 Silene Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
241000269319 Squalius cephalus Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 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
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
GLYOPNLBKCBTMI-UHFFFAOYSA-N [2-chloro-2-(1-chloro-2-phenylethoxy)ethyl]benzene Chemical compound C=1C=CC=CC=1CC(Cl)OC(Cl)CC1=CC=CC=C1 GLYOPNLBKCBTMI-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
238000007259 addition reaction Methods 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
230000001780 adrenocortical effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
210000000601 blood cell Anatomy 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
229940116592 central nervous system diagnostic radiopharmaceuticals Drugs 0.000 description 1
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 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
LADPCMZCENPFGV-UHFFFAOYSA-N chloromethoxymethylbenzene Chemical compound ClCOCC1=CC=CC=C1 LADPCMZCENPFGV-UHFFFAOYSA-N 0.000 description 1
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 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
239000000470 constituent Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229960003887 dichlorophen Drugs 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
MIJRFWVFNKQQDK-UHFFFAOYSA-N furoin Chemical compound C=1C=COC=1C(O)C(=O)C1=CC=CO1 MIJRFWVFNKQQDK-UHFFFAOYSA-N 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
230000036541 health Effects 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
208000014674 injury Diseases 0.000 description 1
230000007794 irritation Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
150000002739 metals Chemical class 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
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 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
238000006053 organic reaction Methods 0.000 description 1
230000001151 other effect Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
235000019629 palatability Nutrition 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
208000030428 polyarticular arthritis Diseases 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
125000006684 polyhaloalkyl group Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 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
239000012286 potassium permanganate 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
239000000843 powder Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
230000009467 reduction Effects 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
HJHVQCXHVMGZNC-JCJNLNMISA-M sodium;(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoate Chemical compound [Na+].O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C([O-])=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C HJHVQCXHVMGZNC-JCJNLNMISA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000005477 standard model Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
230000006103 sulfonylation Effects 0.000 description 1
238000005694 sulfonylation reaction Methods 0.000 description 1
230000001629 suppression Effects 0.000 description 1
230000008961 swelling Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
238000010998 test method Methods 0.000 description 1
UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000008736 traumatic injury Effects 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
230000000007 visual effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
- 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
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/84—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pain & Pain Management (AREA)
Pharmacology & Pharmacy (AREA)
Rheumatology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA296,606A 1977-02-09 1978-02-07 Anti-inflammatory-4,5-dicyclic-2-(substituted thio) imidazoles and their corresponding sulfoxides and sulfones Expired CA1105024A (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US76722077A	1977-02-09	1977-02-09
US767,220		1977-02-09
US865,832		1978-01-05
US05/865,832 US4159338A (en)	1977-02-09	1978-01-05	Antiinflammatory-4,5-dicyclic-2-(substituted thio)-imidazoles and their corresponding sulfoxides and sulfones

Publications (1)

Publication Number	Publication Date
CA1105024A true CA1105024A (en)	1981-07-14

Family

ID=27117879

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA296,606A Expired CA1105024A (en)	1977-02-09	1978-02-07	Anti-inflammatory-4,5-dicyclic-2-(substituted thio) imidazoles and their corresponding sulfoxides and sulfones

Country Status (26)

Country	Link
JP (1)	JPS53130664A (de)
AR (1)	AR219310A1 (de)
AT (1)	AT361470B (de)
AU (1)	AU517028B2 (de)
CA (1)	CA1105024A (de)
CH (1)	CH644108A5 (de)
DE (1)	DE2805167A1 (de)
DK (1)	DK16778A (de)
ES (1)	ES466794A1 (de)
FI (1)	FI69462C (de)
FR (1)	FR2380275A1 (de)
GB (1)	GB1564184A (de)
GR (1)	GR64142B (de)
HU (1)	HU178211B (de)
IE (1)	IE46187B1 (de)
IL (1)	IL53995A (de)
IT (1)	IT1092588B (de)
LU (1)	LU79024A1 (de)
MX (1)	MX5933E (de)
NL (1)	NL7801453A (de)
NO (1)	NO148265C (de)
NZ (1)	NZ186410A (de)
PH (1)	PH13852A (de)
PT (1)	PT67626B (de)
SE (1)	SE7801467L (de)
YU (1)	YU28878A (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0004648B1 (de) *	1978-04-11	1982-08-25	Ciba-Geigy Ag	Neue Mercaptoimidazolderivate, Verfahren zu deren Herstellung, Mercaptoimidazolderivate zur Behandlung entzündlicher Erkrankungen und diese enthaltende pharmazeutische Präparate
US4199592A (en) *	1978-08-29	1980-04-22	E. I. Du Pont De Nemours And Company	Antiinflammatory 4,5-diaryl-2-nitroimidazoles
DK337779A (da) *	1978-10-02	1980-04-03	Du Pont	Fremgangsmaade til fremstilling af antiinflammatoriske 2-substituerede 1h-phenantro (9,10)-imidazoler
AT374198B (de) *	1979-04-10	1984-03-26	Ciba Geigy Ag	Verfahren zur herstellung neuer 2-substituierter mercaptoimidazolderivate, ihrer n-oxyde und ihrer salze
FI850995L (fi) *	1984-03-16	1985-09-17	Ciba Geigy Ag	Foerfarande foer framstaellning av nya 3-merkapto-1,2,4-triazacykloalkadienderivat.
US6040320A (en) *	1997-06-30	2000-03-21	Ortho-Mcneil Pharmaceutical, Inc.	2-substituted imidazoles useful in the treatment of inflammatory diseases
DE10107683A1 (de)	2001-02-19	2002-08-29	Merckle Gmbh Chem Pharm Fabrik	2-Thio-substituierte Imidazolderivate und ihre Verwendung in der Pharmazie

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2981739A (en) *	1958-01-27	1961-04-25	Diamond Alkali Co	Certain alpha-haloaldehyde addition products of ethylenethioureas and process
US3714179A (en) *	1970-09-08	1973-01-30	Searle & Co	1-alkyl-2-furfurylthioimidazoles and congeners
JPS5343958B2 (de) *	1972-07-29	1978-11-24
SE428686B (sv) *	1975-08-11	1983-07-18	Du Pont	Forfarande for framstellning av antiinflammatoriskt aktiva imidazoler

1978
- 1978-01-13 DK DK16778A patent/DK16778A/da not_active Application Discontinuation
- 1978-02-06 PT PT67626A patent/PT67626B/pt unknown
- 1978-02-07 IT IT7820078A patent/IT1092588B/it active
- 1978-02-07 CA CA296,606A patent/CA1105024A/en not_active Expired
- 1978-02-08 SE SE7801467A patent/SE7801467L/xx unknown
- 1978-02-08 NO NO780433A patent/NO148265C/no unknown
- 1978-02-08 AT AT86978A patent/AT361470B/de not_active IP Right Cessation
- 1978-02-08 IE IE279/78A patent/IE46187B1/en unknown
- 1978-02-08 DE DE19782805167 patent/DE2805167A1/de not_active Withdrawn
- 1978-02-08 AU AU33096/78A patent/AU517028B2/en not_active Expired
- 1978-02-08 LU LU79024A patent/LU79024A1/xx unknown
- 1978-02-08 NZ NZ186410A patent/NZ186410A/xx unknown
- 1978-02-08 ES ES466794A patent/ES466794A1/es not_active Expired
- 1978-02-08 IL IL53995A patent/IL53995A/xx unknown
- 1978-02-08 GB GB5098/78A patent/GB1564184A/en not_active Expired
- 1978-02-08 NL NL7801453A patent/NL7801453A/xx not_active Application Discontinuation
- 1978-02-08 YU YU00288/78A patent/YU28878A/xx unknown
- 1978-02-08 MX MX786829U patent/MX5933E/es unknown
- 1978-02-08 FR FR7803518A patent/FR2380275A1/fr active Granted
- 1978-02-09 HU HU78DU279A patent/HU178211B/hu unknown
- 1978-02-09 FI FI780428A patent/FI69462C/fi not_active IP Right Cessation
- 1978-02-09 GR GR55396A patent/GR64142B/el unknown
- 1978-02-09 JP JP1304678A patent/JPS53130664A/ja active Pending
- 1978-02-09 PH PH20771A patent/PH13852A/en unknown
- 1978-02-09 CH CH147478A patent/CH644108A5/de not_active IP Right Cessation
- 1978-02-09 AR AR271048A patent/AR219310A1/es active

Also Published As

Publication number	Publication date
IE46187B1 (en)	1983-03-23
NO780433L (no)	1978-08-10
DK16778A (da)	1978-08-10
FR2380275A1 (fr)	1978-09-08
NO148265B (no)	1983-05-30
IT1092588B (it)	1985-07-12
FI780428A7 (fi)	1978-08-10
LU79024A1 (fr)	1979-05-25
MX5933E (es)	1984-08-30
DE2805167A1 (de)	1978-08-10
IL53995A (en)	1982-02-28
NO148265C (no)	1983-09-07
SE7801467L (sv)	1978-08-10
JPS53130664A (en)	1978-11-14
AT361470B (de)	1981-03-10
CH644108A5 (en)	1984-07-13
ES466794A1 (es)	1979-08-01
HU178211B (en)	1982-03-28
FI69462B (fi)	1985-10-31
GB1564184A (en)	1980-04-02
IT7820078A0 (it)	1978-02-07
FR2380275B1 (de)	1982-01-08
PH13852A (en)	1980-10-22
AU3309678A (en)	1979-08-16
GR64142B (en)	1980-01-28
PT67626B (en)	1979-07-17
PT67626A (en)	1978-03-01
FI69462C (fi)	1986-02-10
IL53995A0 (en)	1978-04-30
ATA86978A (de)	1980-08-15
NL7801453A (nl)	1978-08-11
IE780279L (en)	1978-08-09
NZ186410A (en)	1979-12-11
AU517028B2 (en)	1981-07-02
AR219310A1 (es)	1980-08-15
YU28878A (en)	1983-01-21

Legal Events

Date	Code	Title	Description
1998-07-14	MKEX	Expiry

Publication	Publication Date	Title
US4302461A (en)	1981-11-24	Antiinflammatory 5-substituted-2,3-diarylthiophenes
US4175127A (en)	1979-11-20	Pyridyl substituted 2,3-dihydroimidazo[2,1-b]thiazoles
US4125530A (en)	1978-11-14	Trifluoromethylimidazoles and a method for their preparation
US5001136A (en)	1991-03-19	Leukotriene-synthesis-inhibiting 2-substitutedmethylamino-5-(hydroxy or alkoxy)pyridines
US4182769A (en)	1980-01-08	Anti-inflammatory 1-substituted-4,5-diaryl-2-(substituted-thio) imidazoles and their corresponding sulfoxides and sulfones
US4198421A (en)	1980-04-15	Antiinflammatory 2-substituted-dibenzo[2,3:6,7]oxepino[4,5-d]imidazoles
US4159329A (en)	1979-06-26	4-Pyrimidones compositions, and methods of use
US4190666A (en)	1980-02-26	Anti-inflammatory 4,5-diarly-2-(substituted-thio)imidazoles and their corresponding sulfoxides and sulfones
US4882342A (en)	1989-11-21	5-alkylbenzimidazoles, method of use and pharmaceutical compositions
US4438117A (en)	1984-03-20	2-Substituted thio-4,5-diarylpyrimidines
US4159338A (en)	1979-06-26	Antiinflammatory-4,5-dicyclic-2-(substituted thio)-imidazoles and their corresponding sulfoxides and sulfones
US4535092A (en)	1985-08-13	Acylanilides having antiandrogenic activity
US4710506A (en)	1987-12-01	Antihypertensive thienopyridines
HU182018B (en)	1983-12-28	Process for producing new s-substituted 2-mercapto-imidazol derivatives
US4218452A (en)	1980-08-19	Substituted 4-pyrimidone compounds, compositions and methods of use
EP0171739B1 (de)	1990-01-10	Imidazo[1,5-a]pyrimidinderivate und Verfahren zu ihrer Herstellung
EP0087629B1 (de)	1986-01-15	Entzündungshemmende und/oder Schmerzstillende 2,3-Diaryl-5-halo thiophene
CA1074327A (en)	1980-03-25	Anti-inflammatory imidazoles
US3444175A (en)	1969-05-13	Certain picolylmethyl sulfones
IE46187B1 (en)	1983-03-23	Anti-inflammatory 4,5-dicyclic-2-(substituted thio)-imidazoles and their corresponding sulfoxides and sulfones
EP0005156B1 (de)	1982-09-22	4,5-Diaryl-2-(substituierte-thio)pyrrole und ihre übereinstimmenden Sulfoxyde und Sulfone, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitungen
US4215135A (en)	1980-07-29	Antiinflammatory 2-substituted-1H-phenanthro[9,10-d]imidazoles
EP0011115B1 (de)	1982-01-20	Antiinflammatorische 2-substituierte-1H-Phenanthro (9,10-d)imidazole, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen
US3551444A (en)	1970-12-29	Lower alkyl sulfinyl methyl imidazoles
US4458079A (en)	1984-07-03	Sulfur-containing imidazoles