LU82844A1 - Nouveaux composes heterocycliques azotes anti-inflammatoires et immunoregulateurs et composition pharmaceutique les contenant - Google Patents
Nouveaux composes heterocycliques azotes anti-inflammatoires et immunoregulateurs et composition pharmaceutique les contenant Download PDFInfo
- Publication number
- LU82844A1 LU82844A1 LU82844A LU82844A LU82844A1 LU 82844 A1 LU82844 A1 LU 82844A1 LU 82844 A LU82844 A LU 82844A LU 82844 A LU82844 A LU 82844A LU 82844 A1 LU82844 A1 LU 82844A1
- Authority
- LU
- Luxembourg
- Prior art keywords
- oil
- pyridine
- mmol
- solution
- reaction mixture
- Prior art date
Links
- -1 NITROGEN HETEROCYCLIC COMPOUNDS Chemical class 0.000 title claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 title claims description 6
- 230000003110 anti-inflammatory effect Effects 0.000 title abstract description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title description 9
- 239000008194 pharmaceutical composition Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 24
- OYJOLTPPSDAGJC-UHFFFAOYSA-N 2-(pyridin-4-ylmethylsulfanyl)ethanol Chemical class OCCSCC1=CC=NC=C1 OYJOLTPPSDAGJC-UHFFFAOYSA-N 0.000 abstract description 12
- 230000004957 immunoregulator effect Effects 0.000 abstract description 11
- PGTWETKOKSJIQO-UHFFFAOYSA-N 1-(pyridin-4-ylmethylsulfanyl)propan-2-ol Chemical compound CC(O)CSCC1=CC=NC=C1 PGTWETKOKSJIQO-UHFFFAOYSA-N 0.000 abstract description 3
- IIJADHQFJSSMHU-UHFFFAOYSA-N 2-(pyrimidin-4-ylmethylsulfanyl)ethanol Chemical compound OCCSCC1=CC=NC=N1 IIJADHQFJSSMHU-UHFFFAOYSA-N 0.000 abstract description 3
- BAPIUJYONJVSKH-UHFFFAOYSA-N 3-(pyridin-4-ylmethylsulfanyl)butan-2-ol Chemical compound CC(O)C(C)SCC1=CC=NC=C1 BAPIUJYONJVSKH-UHFFFAOYSA-N 0.000 abstract description 3
- ZQADQPAQGWNURI-UHFFFAOYSA-N 3-(pyridin-4-ylmethylsulfanyl)propane-1,2-diol Chemical compound OCC(O)CSCC1=CC=NC=C1 ZQADQPAQGWNURI-UHFFFAOYSA-N 0.000 abstract description 3
- KHJJJVWKGALGAY-UHFFFAOYSA-N 2-(pyridin-4-ylmethylsulfanyl)phenol Chemical compound OC1=CC=CC=C1SCC1=CC=NC=C1 KHJJJVWKGALGAY-UHFFFAOYSA-N 0.000 abstract description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 112
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 78
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- 239000003921 oil Substances 0.000 description 73
- 235000019198 oils Nutrition 0.000 description 73
- 239000000243 solution Substances 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 61
- 239000011541 reaction mixture Substances 0.000 description 48
- 238000007792 addition Methods 0.000 description 33
- 238000000034 method Methods 0.000 description 31
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000047 product Substances 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000002329 infrared spectrum Methods 0.000 description 22
- 239000012299 nitrogen atmosphere Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000003480 eluent Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 230000009467 reduction Effects 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 239000005909 Kieselgur Substances 0.000 description 10
- 206010030113 Oedema Diseases 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 239000010408 film Substances 0.000 description 10
- 150000004820 halides Chemical class 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- YUWAUUTYKFAJBH-UHFFFAOYSA-N pyridin-4-ylmethanethiol Chemical compound SCC1=CC=NC=C1 YUWAUUTYKFAJBH-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- 150000004678 hydrides Chemical class 0.000 description 9
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 210000003743 erythrocyte Anatomy 0.000 description 8
- 150000004795 grignard reagents Chemical class 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-UHFFFAOYSA-N 0.000 description 7
- 239000007818 Grignard reagent Substances 0.000 description 7
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 230000028993 immune response Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000001819 mass spectrum Methods 0.000 description 7
- 150000003222 pyridines Chemical group 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 description 6
- 239000002260 anti-inflammatory agent Substances 0.000 description 6
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 6
- 229960002170 azathioprine Drugs 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 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 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000000679 carrageenan Substances 0.000 description 5
- 229940113118 carrageenan Drugs 0.000 description 5
- 235000010418 carrageenan Nutrition 0.000 description 5
- 229920001525 carrageenan Polymers 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 229960002895 phenylbutazone Drugs 0.000 description 5
- 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 5
- 150000003230 pyrimidines Chemical group 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 5
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 5
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 4
- DINNJAVAAQMMHV-UHFFFAOYSA-N 4-pyridin-4-ylbutane-2-thione Chemical compound CC(=S)CCC1=CC=NC=C1 DINNJAVAAQMMHV-UHFFFAOYSA-N 0.000 description 4
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 238000003810 ethyl acetate extraction Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 4
- VBAOEVKQBLGWTH-UHFFFAOYSA-N 2-pyridin-4-ylethanethiol Chemical compound SCCC1=CC=NC=C1 VBAOEVKQBLGWTH-UHFFFAOYSA-N 0.000 description 3
- VAJUUDUWDNCECT-UHFFFAOYSA-N 4-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=NC=C1 VAJUUDUWDNCECT-UHFFFAOYSA-N 0.000 description 3
- KFDVPJUYSDEJTH-UHFFFAOYSA-N 4-ethenylpyridine Chemical compound C=CC1=CC=NC=C1 KFDVPJUYSDEJTH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 3
- 239000012448 Lithium borohydride Substances 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 241001494479 Pecora 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
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 229960000905 indomethacin Drugs 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229960001614 levamisole Drugs 0.000 description 3
- BVVOVEFLZPQKOL-UHFFFAOYSA-N methyl 2-phenyl-2-(pyridin-4-ylmethylsulfanyl)acetate Chemical compound C=1C=CC=CC=1C(C(=O)OC)SCC1=CC=NC=C1 BVVOVEFLZPQKOL-UHFFFAOYSA-N 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 201000003068 rheumatic fever Diseases 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011343 solid material Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000001562 ulcerogenic effect Effects 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- UKNOHZCPWSXJPL-UHFFFAOYSA-N 1-phenyl-2-(pyridin-4-ylmethylsulfanyl)propan-1-ol Chemical compound C=1C=CC=CC=1C(O)C(C)SCC1=CC=NC=C1 UKNOHZCPWSXJPL-UHFFFAOYSA-N 0.000 description 2
- IYQDVZPIZGYHJI-UHFFFAOYSA-N 2-(pyridin-4-ylmethylsulfanyl)ethyl acetate Chemical compound CC(=O)OCCSCC1=CC=NC=C1 IYQDVZPIZGYHJI-UHFFFAOYSA-N 0.000 description 2
- DKBVJOOKZMTTMK-UHFFFAOYSA-N 2-methyl-1-(pyridin-4-ylmethylsulfanyl)propan-2-ol Chemical compound CC(C)(O)CSCC1=CC=NC=C1 DKBVJOOKZMTTMK-UHFFFAOYSA-N 0.000 description 2
- VMKYTRPNOVFCGZ-UHFFFAOYSA-N 2-sulfanylphenol Chemical compound OC1=CC=CC=C1S VMKYTRPNOVFCGZ-UHFFFAOYSA-N 0.000 description 2
- OKLBYPMDIRXALH-UHFFFAOYSA-N 4-(bromomethyl)pyrimidine Chemical compound BrCC1=CC=NC=N1 OKLBYPMDIRXALH-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
- 206010015150 Erythema Diseases 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- XUPKOLLGVILXSP-UHFFFAOYSA-N [amino(sulfanyl)methylidene]-(pyridin-4-ylmethyl)azanium;chloride;hydrochloride Chemical compound Cl.Cl.SC(=N)NCC1=CC=NC=C1 XUPKOLLGVILXSP-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- CMJVTGWDYPQSTL-UHFFFAOYSA-N dihydrogen phosphate;2-(pyridin-1-ium-4-ylmethylsulfanyl)ethanol Chemical compound OP(O)(O)=O.OCCSCC1=CC=NC=C1 CMJVTGWDYPQSTL-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- XRDQIFGHTFLEHD-UHFFFAOYSA-N ethyl 2-(pyridin-4-ylmethylsulfanyl)propanoate Chemical compound CCOC(=O)C(C)SCC1=CC=NC=C1 XRDQIFGHTFLEHD-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 150000005217 methyl ethers Chemical class 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 229960002702 piroxicam Drugs 0.000 description 2
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- ZGXKOLGDFWQRMM-UHFFFAOYSA-N pyridin-4-ylmethyl acetate Chemical compound CC(=O)OCC1=CC=NC=C1 ZGXKOLGDFWQRMM-UHFFFAOYSA-N 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- ZFQUWZCCXOTRJG-UHFFFAOYSA-M sodium;2-(pyridin-4-ylmethylsulfanyl)propanoate Chemical compound [Na+].[O-]C(=O)C(C)SCC1=CC=NC=C1 ZFQUWZCCXOTRJG-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- QYIGFZOHYGYBLX-SSDOTTSWSA-N (2r)-2-phenyl-2-sulfanylacetic acid Chemical compound OC(=O)[C@H](S)C1=CC=CC=C1 QYIGFZOHYGYBLX-SSDOTTSWSA-N 0.000 description 1
- JLIFSYCXGJGLGE-UHFFFAOYSA-N (4-methylpyridin-3-yl) acetate Chemical compound CC(=O)OC1=CN=CC=C1C JLIFSYCXGJGLGE-UHFFFAOYSA-N 0.000 description 1
- USVCRBGYQRVTNK-UHFFFAOYSA-N 1-Mercapto-2-propanone Chemical compound CC(=O)CS USVCRBGYQRVTNK-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical class CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- SLHYXNYHQSTFMA-UHFFFAOYSA-N 1-phenyl-2-(pyridin-4-ylmethylsulfanyl)ethanol Chemical compound C=1C=CC=CC=1C(O)CSCC1=CC=NC=C1 SLHYXNYHQSTFMA-UHFFFAOYSA-N 0.000 description 1
- PFMZKLLNBVGYQB-UHFFFAOYSA-N 1-phenyl-2-(pyridin-4-ylmethylsulfanyl)ethanone Chemical compound C=1C=CC=CC=1C(=O)CSCC1=CC=NC=C1 PFMZKLLNBVGYQB-UHFFFAOYSA-N 0.000 description 1
- RVSLGHONXIRODY-UHFFFAOYSA-N 2-(2-pyridin-4-ylethylsulfanyl)ethanol Chemical compound OCCSCCC1=CC=NC=C1 RVSLGHONXIRODY-UHFFFAOYSA-N 0.000 description 1
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
- JXIVUVCIBGRJQU-UHFFFAOYSA-N 2-(pyridin-2-ylmethylsulfanyl)ethanol Chemical compound OCCSCC1=CC=CC=N1 JXIVUVCIBGRJQU-UHFFFAOYSA-N 0.000 description 1
- SAWSUHYFYCIVHL-UHFFFAOYSA-N 2-(pyridin-3-ylmethylsulfanyl)ethanol Chemical compound OCCSCC1=CC=CN=C1 SAWSUHYFYCIVHL-UHFFFAOYSA-N 0.000 description 1
- RDWSWEZQTVXLBM-UHFFFAOYSA-N 2-(pyridin-4-ylmethylsulfanyl)propan-1-ol Chemical compound OCC(C)SCC1=CC=NC=C1 RDWSWEZQTVXLBM-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- XQJAHBHCLXUGEP-UHFFFAOYSA-N 2-bromo-1-(4-methoxyphenyl)ethanone Chemical compound COC1=CC=C(C(=O)CBr)C=C1 XQJAHBHCLXUGEP-UHFFFAOYSA-N 0.000 description 1
- MBUPVGIGAMCMBT-UHFFFAOYSA-N 2-bromo-1-(4-nitrophenyl)ethanone Chemical compound [O-][N+](=O)C1=CC=C(C(=O)CBr)C=C1 MBUPVGIGAMCMBT-UHFFFAOYSA-N 0.000 description 1
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
- VHXDADVHQVXSKC-UHFFFAOYSA-N 2-methoxyethanethiol Chemical compound COCCS VHXDADVHQVXSKC-UHFFFAOYSA-N 0.000 description 1
- LAZZBEQTMYZKFN-UHFFFAOYSA-N 2-oxo-3h-1-benzofuran-3-carboxamide Chemical class C1=CC=C2C(C(=O)N)C(=O)OC2=C1 LAZZBEQTMYZKFN-UHFFFAOYSA-N 0.000 description 1
- VWKXFSPPLHTWHE-UHFFFAOYSA-N 2-phenyl-2-(pyridin-4-ylmethylsulfanyl)ethanol Chemical compound C=1C=CC=CC=1C(CO)SCC1=CC=NC=C1 VWKXFSPPLHTWHE-UHFFFAOYSA-N 0.000 description 1
- QNNVICQPXUUBSN-UHFFFAOYSA-N 2-sulfanylpropan-1-ol Chemical compound CC(S)CO QNNVICQPXUUBSN-UHFFFAOYSA-N 0.000 description 1
- GHNLJDPNIAIWOQ-UHFFFAOYSA-N 2h-1$l^{6},2-benzothiazine 1,1-dioxide Chemical class C1=CC=C2S(=O)(=O)NC=CC2=C1 GHNLJDPNIAIWOQ-UHFFFAOYSA-N 0.000 description 1
- AFVLLDNHUWLBJZ-UHFFFAOYSA-N 3-(1-methylimidazol-2-yl)sulfanylpropanenitrile Chemical compound CN1C=CN=C1SCCC#N AFVLLDNHUWLBJZ-UHFFFAOYSA-N 0.000 description 1
- BDHRMEIYRGIWAH-UHFFFAOYSA-N 3-(pyridin-4-ylmethylsulfanyl)propan-1-ol Chemical compound OCCCSCC1=CC=NC=C1 BDHRMEIYRGIWAH-UHFFFAOYSA-N 0.000 description 1
- MJQWABQELVFQJL-UHFFFAOYSA-N 3-Mercapto-2-butanol Chemical compound CC(O)C(C)S MJQWABQELVFQJL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OUCSZKWRKZPPMC-UHFFFAOYSA-N 3-pyridin-4-ylsulfanylpropan-1-ol Chemical compound OCCCSC1=CC=NC=C1 OUCSZKWRKZPPMC-UHFFFAOYSA-N 0.000 description 1
- PSVLZDPFBODRQO-UHFFFAOYSA-N 4-(2-methoxyethylsulfanylmethyl)pyridine Chemical compound COCCSCC1=CC=NC=C1 PSVLZDPFBODRQO-UHFFFAOYSA-N 0.000 description 1
- KRLKXOLFFQWKPZ-UHFFFAOYSA-N 4-(bromomethyl)pyridine Chemical compound BrCC1=CC=NC=C1 KRLKXOLFFQWKPZ-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- IWYYIZOHWPCALJ-UHFFFAOYSA-N 4-methyl-1-oxidopyridin-1-ium Chemical compound CC1=CC=[N+]([O-])C=C1 IWYYIZOHWPCALJ-UHFFFAOYSA-N 0.000 description 1
- LVILGAOSPDLNRM-UHFFFAOYSA-N 4-methylpyrimidine Chemical compound CC1=CC=NC=N1 LVILGAOSPDLNRM-UHFFFAOYSA-N 0.000 description 1
- IJJWOSAXNHWBPR-HUBLWGQQSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-hydrazinyl-6-oxohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCC(=O)NN)SC[C@@H]21 IJJWOSAXNHWBPR-HUBLWGQQSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000008365 aromatic ketones Chemical class 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- QLFNUXTWJGXNLH-UHFFFAOYSA-N bis(2-methoxyethoxy)alumane Chemical compound COCCO[AlH]OCCOC QLFNUXTWJGXNLH-UHFFFAOYSA-N 0.000 description 1
- UPBWIICFGYMCPC-UHFFFAOYSA-N bis(2-methoxyethoxy)aluminum Chemical compound COCCO[Al]OCCOC UPBWIICFGYMCPC-UHFFFAOYSA-N 0.000 description 1
- BKWBNPHAXJIXSB-UHFFFAOYSA-N bis(2-methoxyethyl)aluminum Chemical compound COCC[Al]CCOC BKWBNPHAXJIXSB-UHFFFAOYSA-N 0.000 description 1
- AOJDZKCUAATBGE-UHFFFAOYSA-N bromomethane Chemical compound Br[CH2] AOJDZKCUAATBGE-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical class SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000003944 halohydrins Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- AJQVXEIIIQBPAL-UHFFFAOYSA-N o-methyl 2-phenyl-3-pyridin-4-ylpropanethioate Chemical compound C=1C=CC=CC=1C(C(=S)OC)CC1=CC=NC=C1 AJQVXEIIIQBPAL-UHFFFAOYSA-N 0.000 description 1
- UJTMLNARSPORHR-UHFFFAOYSA-N oc2h5 Chemical compound C=C=[O+] UJTMLNARSPORHR-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000007793 ph indicator Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 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
- HOJLDGRYURJOJS-UHFFFAOYSA-N phosphoric acid;pyridine Chemical compound OP(O)(O)=O.C1=CC=NC=C1 HOJLDGRYURJOJS-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical compound CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- HSXXTCFMNNMOOM-UHFFFAOYSA-N pyridin-4-ylmethylsulfanyl propanoate Chemical compound C(CC)(=O)OSCC1=CC=NC=C1 HSXXTCFMNNMOOM-UHFFFAOYSA-N 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- RVEZZJVBDQCTEF-UHFFFAOYSA-N sulfenic acid Chemical class SO RVEZZJVBDQCTEF-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01D—HARVESTING; MOWING
- A01D34/00—Mowers; Mowing apparatus of harvesters
- A01D34/001—Accessories not otherwise provided for
- A01D34/003—Means for cleaning the machine
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C33/00—Moulds or cores; Details thereof or accessories therefor
- B29C33/56—Coatings, e.g. enameled or galvanised; Releasing, lubricating or separating agents
- B29C33/60—Releasing, lubricating or separating agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C70/00—Shaping composites, i.e. plastics material comprising reinforcements, fillers or preformed parts, e.g. inserts
- B29C70/68—Shaping composites, i.e. plastics material comprising reinforcements, fillers or preformed parts, e.g. inserts by incorporating or moulding on preformed parts, e.g. inserts or layers, e.g. foam blocks
- B29C70/84—Shaping composites, i.e. plastics material comprising reinforcements, fillers or preformed parts, e.g. inserts by incorporating or moulding on preformed parts, e.g. inserts or layers, e.g. foam blocks by moulding material on preformed parts to be joined
-
- 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
- C07D213/54—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
- C07D213/55—Acids; Esters
-
- 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
- C07D213/60—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 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16C—SHAFTS; FLEXIBLE SHAFTS; ELEMENTS OR CRANKSHAFT MECHANISMS; ROTARY BODIES OTHER THAN GEARING ELEMENTS; BEARINGS
- F16C11/00—Pivots; Pivotal connections
- F16C11/04—Pivotal connections
- F16C11/06—Ball-joints; Other joints having more than one degree of angular freedom, i.e. universal joints
- F16C11/0604—Construction of the male part
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16C—SHAFTS; FLEXIBLE SHAFTS; ELEMENTS OR CRANKSHAFT MECHANISMS; ROTARY BODIES OTHER THAN GEARING ELEMENTS; BEARINGS
- F16C11/00—Pivots; Pivotal connections
- F16C11/04—Pivotal connections
- F16C11/06—Ball-joints; Other joints having more than one degree of angular freedom, i.e. universal joints
- F16C11/068—Special features relating to lubrication
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Environmental Sciences (AREA)
- Composite Materials (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8501179 | 1979-10-15 | ||
US06/085,011 US4246263A (en) | 1979-10-15 | 1979-10-15 | Antiinflammatory and immunoregulatory pyrimidines, their method of use and pharmaceutical compositions |
Publications (1)
Publication Number | Publication Date |
---|---|
LU82844A1 true LU82844A1 (fr) | 1981-06-04 |
Family
ID=22188737
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LU82844A LU82844A1 (fr) | 1979-10-15 | 1980-10-13 | Nouveaux composes heterocycliques azotes anti-inflammatoires et immunoregulateurs et composition pharmaceutique les contenant |
Country Status (39)
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4371696A (en) * | 1980-07-14 | 1983-02-01 | Pfizer Inc. | Certain pyridine methylthio acetaldehyde derivatives and non-cyclic and cyclic acetals thereof |
GB8405896D0 (en) * | 1984-03-07 | 1984-04-11 | Sandoz Ltd | Organic compounds |
WO1987007842A1 (en) * | 1986-06-17 | 1987-12-30 | Biogen N.V. | Combinations of gamma interferons and anti-inflammatory or anti-pyretic agents and methods for treating diseases |
WO2003024955A2 (en) * | 2001-09-18 | 2003-03-27 | Sunesis Pharmaceuticals, Inc. | Small molecule inhibitors of caspases |
CA2599169C (en) * | 2005-02-25 | 2013-10-22 | Temple University - Of The Commonwealth System Of Higher Education | Synthesis of (e)-alpha, beta unsaturated sulfides, sulfones, sulfoxides and sulfonamides |
JP5287033B2 (ja) * | 2007-08-23 | 2013-09-11 | 住友化学株式会社 | 含フッ素有機硫黄化合物およびその有害節足動物防除剤 |
CN108530606B (zh) * | 2018-04-19 | 2020-11-20 | 山东师范大学 | 一种pH敏感性医用聚氨酯脲材料及其制备方法 |
CA3115629A1 (en) | 2018-10-08 | 2020-04-16 | Ecolab Usa Inc. | Sulfide-based compounds and uses thereof |
CN110483740B (zh) * | 2019-08-12 | 2021-08-27 | 山东师范大学 | 一种聚合物、pH敏感性纳米囊泡及制备方法与应用 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3409626A (en) * | 1963-09-17 | 1968-11-05 | Neisler Lab Inc | Indolylethyl pyridinium quaternary ammonium compounds |
NL144484B (nl) * | 1967-07-26 | 1975-01-15 | Merck & Co Inc | Werkwijze ter bereiding van een geneesmiddel met anti-anflammatoire werking, alsmede werkwijze ter bereiding van de anti-inflammatoir werkzame aralkylmercaptoaminozuren. |
US3558640A (en) * | 1967-12-20 | 1971-01-26 | Merck & Co Inc | Certain pyridyl and thiazolyl methylthiopropionic acids and derivatives |
US3636074A (en) * | 1968-08-05 | 1972-01-18 | Hooker Chemical Corp | Novel mercaptophenol derivatives |
US3591584A (en) | 1968-08-27 | 1971-07-06 | Pfizer | Benzothiazine dioxides |
US3818009A (en) * | 1969-12-29 | 1974-06-18 | Lilly Co Eli | Alpha, alpha-disubstituted-5-pyrimidinemethanes |
US3676463A (en) | 1970-10-15 | 1972-07-11 | Pfizer | Oxobenzofuran carboxamides |
US3707475A (en) | 1970-11-16 | 1972-12-26 | Pfizer | Antiinflammatory imidazoles |
JPS52125170A (en) * | 1976-04-12 | 1977-10-20 | Yoshitomi Pharmaceut Ind Ltd | Pyridine derivatives |
-
1979
- 1979-10-15 US US06/085,011 patent/US4246263A/en not_active Expired - Lifetime
-
1980
- 1980-08-16 IN IN597/DEL/80A patent/IN154554B/en unknown
- 1980-09-24 DK DK403080A patent/DK152427C/da not_active IP Right Cessation
- 1980-10-09 AR AR282823A patent/AR226864A1/es active
- 1980-10-10 CA CA000362238A patent/CA1156231A/en not_active Expired
- 1980-10-11 GR GR63147A patent/GR70311B/el unknown
- 1980-10-13 DE DE19803038593 patent/DE3038593A1/de active Granted
- 1980-10-13 AT AT0508980A patent/AT377513B/de not_active IP Right Cessation
- 1980-10-13 NZ NZ195246A patent/NZ195246A/en unknown
- 1980-10-13 YU YU2626/80A patent/YU41740B/xx unknown
- 1980-10-13 GB GB8137997A patent/GB2092133B/en not_active Expired
- 1980-10-13 LU LU82844A patent/LU82844A1/fr unknown
- 1980-10-13 IL IL61261A patent/IL61261A/xx unknown
- 1980-10-13 GB GB8032971A patent/GB2061928B/en not_active Expired
- 1980-10-14 EG EG80638A patent/EG14676A/xx active
- 1980-10-14 SU SU802993951A patent/SU1083907A3/ru active
- 1980-10-14 NL NL8005652A patent/NL8005652A/nl not_active Application Discontinuation
- 1980-10-14 IT IT25324/80A patent/IT1195269B/it active
- 1980-10-14 ES ES495932A patent/ES8201972A1/es not_active Expired
- 1980-10-14 DD DD80224544A patent/DD154816B3/de not_active IP Right Cessation
- 1980-10-14 IE IE2125/80A patent/IE50665B1/en unknown
- 1980-10-14 FR FR8021931A patent/FR2467199A1/fr active Granted
- 1980-10-14 PH PH24725A patent/PH18277A/en unknown
- 1980-10-14 AU AU63240/80A patent/AU517763B2/en not_active Ceased
- 1980-10-14 BE BE0/202467A patent/BE885709A/fr not_active IP Right Cessation
- 1980-10-14 HU HU802494A patent/HU183233B/hu not_active IP Right Cessation
- 1980-10-14 JP JP14357280A patent/JPS5663962A/ja active Granted
- 1980-10-14 FI FI803239A patent/FI75560C/fi not_active IP Right Cessation
- 1980-10-14 SE SE8007193A patent/SE437023B/sv not_active IP Right Cessation
- 1980-10-14 NO NO803073A patent/NO156566C/no unknown
- 1980-10-14 PT PT71917A patent/PT71917B/pt unknown
- 1980-10-14 HU HU83101A patent/HU191824B/hu not_active IP Right Cessation
- 1980-10-14 ZA ZA00806306A patent/ZA806306B/xx unknown
- 1980-10-15 PL PL1980227307A patent/PL125314B1/pl unknown
- 1980-10-15 KR KR1019800003966A patent/KR840001614B1/ko not_active Expired
- 1980-10-15 CH CH771980A patent/CH646425A5/fr not_active IP Right Cessation
- 1980-10-15 CS CS806985A patent/CS226020B2/cs unknown
- 1980-10-15 PL PL1980231782A patent/PL125402B1/pl unknown
-
1981
- 1981-09-08 CS CS816610A patent/CS226034B2/cs unknown
- 1981-09-16 ES ES505544A patent/ES505544A0/es active Granted
- 1981-11-04 SU SU813349450A patent/SU1144617A3/ru active
-
1982
- 1982-01-18 DD DD82236826A patent/DD202543A5/de not_active IP Right Cessation
- 1982-02-18 AR AR288463A patent/AR227089A1/es active
- 1982-02-18 AR AR288464A patent/AR227576A1/es active
- 1982-12-01 YU YU2668/82A patent/YU42059B/xx unknown
-
1983
- 1983-07-22 AT AT0268783A patent/AT379801B/de not_active IP Right Cessation
-
1984
- 1984-06-05 IN IN464/DEL/84A patent/IN163553B/en unknown
- 1984-08-13 SG SG563/84A patent/SG56384G/en unknown
- 1984-08-22 KR KR1019840005076A patent/KR840001615B1/ko not_active Expired
- 1984-09-24 KE KE3461A patent/KE3461A/xx unknown
- 1984-09-25 SG SG691/84A patent/SG69184G/en unknown
- 1984-10-05 KE KE3466A patent/KE3466A/xx unknown
-
1985
- 1985-01-03 HK HK11/85A patent/HK1185A/xx unknown
- 1985-12-30 MY MY323/85A patent/MY8500323A/xx unknown
- 1985-12-30 MY MY325/85A patent/MY8500325A/xx unknown
-
1987
- 1987-09-17 HK HK668/87A patent/HK66887A/xx unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0202164B1 (fr) | Dérivés de (benzoyl-4 pipéridino)-2 phenyl-1 alcanols, leur préparation et leur application en thérapeutique | |
EP0350403B1 (fr) | Dérivés de (aza)naphtalènesultame, leurs procédés de préparation et les médicaments les contenant | |
EP0042781B1 (fr) | Nouveaux dérivés de (quinolyl-4)-1 (pipéridyl ou pyrrolidinyl-2 ou -3)-2 ou -3 éthanone ou propanone, procédés pour leur préparation, et leur utilisation comme médicaments | |
EP0001534B1 (fr) | Nouveaux dérivés du pyrrole, leur procédé de préparation et leurs applications en thérapeutique | |
EP0468884B1 (fr) | Nouveaux dérivés de benzimidazole, leur préparation, et leur application en tant que médicaments | |
LU82844A1 (fr) | Nouveaux composes heterocycliques azotes anti-inflammatoires et immunoregulateurs et composition pharmaceutique les contenant | |
EP0031753B1 (fr) | Nouveaux dérivés de la (pipéridyl-4)-2 (quinolyl-4)-1 éthanone, produits intermédiaires et procédés pour leur préparation, et leur utilisation comme médicaments | |
EP0388309A2 (fr) | Nouveaux dérivés du 1h,3h-pyrrolo [1,2-c] thiazolecarboxamide-7, leur préparation et les compositions pharmaceutiques qui les contiennent. | |
EP0418933A1 (fr) | Dérivés d'alcadiènes, leurs préparations, les médicaments les contenant et produits intermédiaires | |
EP0239461A1 (fr) | Dérivés de N-¬¬(hydroxy-2 phényl) (phényl) méthylène amino-2 éthyl acétamide, leur préparation et leur application en thérapeutique | |
EP0366511A1 (fr) | Nouveaux dérivés benzoxazolinoniques, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent | |
EP0410834A1 (fr) | Médicaments à base de dérivés de benzoxadiazine-4, 1, 2 nouveaux dérivés et leurs procédés de préparation | |
CH641798A5 (fr) | Derives de dibenzothiepinne et leur procede de synthese. | |
KR900006724B1 (ko) | 벤조티아진 디옥사이드 유도체 | |
EP0374041A1 (fr) | Médicaments à base de dérivés de la benzothiazolamine-2, dérivés et leur préparation | |
EP0006789A1 (fr) | Composés bis (aryloxyalcanecarboxyliques), leur préparation et leur utilisation en thérapeutique | |
CA2022732A1 (fr) | Derives d'oxazolo pyridines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent | |
FR2509725A1 (fr) | (hydroxyalkyl)phenylsulfures, leurs procedes de preparation et compositions pharmaceutiques les contenant | |
JPS5849369A (ja) | 新規のイミダゾール化合物 | |
EP0294258A1 (fr) | Dérivés d'hydrazine, procédé d'obtention et compositions pharmaceutiques les contenant | |
EP0074873A1 (fr) | Dérivés de phénoxy-3 propanol-2, leur préparation et leur application en thérapeutique | |
CH648483A5 (fr) | Composition pharmaceutique contre l'arthrite rhumatoide. | |
EP0412898A1 (fr) | Nouveaux dérivés d'oxazolo pyridines, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent | |
EP0078765A1 (fr) | Dérivés de p-acylaminophénol à effet thérapeutique, procédé pour leur préparation, et composition à effet thérapeutique contenant lesdits dérivés à titre d'ingrédients pharmacologiquement actifs | |
FR2475543A1 (fr) | Derives benzylideniques, leur preparation et leur application en therapeutique |