SK278012B6 - Thienopyrane derivatives, method of their production and their use - Google Patents
Thienopyrane derivatives, method of their production and their use Download PDFInfo
- Publication number
- SK278012B6 SK278012B6 SK3172-90A SK317290A SK278012B6 SK 278012 B6 SK278012 B6 SK 278012B6 SK 317290 A SK317290 A SK 317290A SK 278012 B6 SK278012 B6 SK 278012B6
- Authority
- SK
- Slovakia
- Prior art keywords
- general formula
- derivatives
- thieno
- compound
- pyran
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000003085 diluting agent Substances 0.000 claims abstract description 5
- 230000004913 activation Effects 0.000 claims abstract description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 3
- 239000000460 chlorine Substances 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 21
- -1 2-oxo-1-pyrrolidinyl Chemical group 0.000 claims description 12
- HJYUNRDQEQBDCG-UHFFFAOYSA-N 5H-thieno[3,2-b]pyran Chemical class C1=CCOC2=C1SC=C2 HJYUNRDQEQBDCG-UHFFFAOYSA-N 0.000 claims description 9
- 108090000862 Ion Channels Proteins 0.000 claims description 3
- 102000004310 Ion Channels Human genes 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000000269 nucleophilic effect Effects 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- ULFGDQDWOJBMLY-YPMHNXCESA-N (6s,7s)-6-hydroxy-5,5-dimethyl-7-(2-oxopyrrolidin-1-yl)-6,7-dihydrothieno[3,2-b]pyran-2-carbonitrile Chemical compound N1([C@@H]2C=3SC(=CC=3OC([C@H]2O)(C)C)C#N)CCCC1=O ULFGDQDWOJBMLY-YPMHNXCESA-N 0.000 claims 1
- MMTVHLPXGYWNOJ-UHFFFAOYSA-N 2h-pyran-2-carboxamide Chemical compound NC(=O)C1OC=CC=C1 MMTVHLPXGYWNOJ-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 11
- 239000012528 membrane Substances 0.000 abstract description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 abstract 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 abstract 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 229910052740 iodine Inorganic materials 0.000 abstract 1
- 239000011630 iodine Substances 0.000 abstract 1
- 239000012038 nucleophile Substances 0.000 abstract 1
- 229930192474 thiophene Natural products 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000013078 crystal Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000012071 phase Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- RUFPSEPHYSMUCR-UHFFFAOYSA-N 2h-pyran-2-carbonitrile Chemical compound N#CC1OC=CC=C1 RUFPSEPHYSMUCR-UHFFFAOYSA-N 0.000 description 6
- 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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 239000003610 charcoal Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- WXWQJUNPKFWAEX-UHFFFAOYSA-N 2h-pyran-2-carbaldehyde Chemical compound O=CC1OC=CC=C1 WXWQJUNPKFWAEX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 239000005662 Paraffin oil Substances 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SDRQQMUJLIEIEO-PWSUYJOCSA-N (6s,7s)-6-hydroxy-5,5-dimethyl-7-(2-oxopyrrolidin-1-yl)-6,7-dihydrothieno[3,2-b]pyran-2-carboxamide Chemical compound N1([C@@H]2C=3SC(=CC=3OC([C@H]2O)(C)C)C(N)=O)CCCC1=O SDRQQMUJLIEIEO-PWSUYJOCSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- WSEQXVZVJXJVFP-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound O1CC2=CC(C#N)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 WSEQXVZVJXJVFP-UHFFFAOYSA-N 0.000 description 1
- JJSCUXAFAJEQGB-UHFFFAOYSA-N 1-isocyanatoethylbenzene Chemical compound O=C=NC(C)C1=CC=CC=C1 JJSCUXAFAJEQGB-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- GQBCZPRINVZQJQ-UHFFFAOYSA-N 3-hydroxythiophene-2-carbaldehyde Chemical compound OC=1C=CSC=1C=O GQBCZPRINVZQJQ-UHFFFAOYSA-N 0.000 description 1
- JIVGFTRLLYSYQT-UHFFFAOYSA-N 5,5-dimethylthieno[3,2-b]pyran Chemical compound C1=CC(C)(C)OC2=C1SC=C2 JIVGFTRLLYSYQT-UHFFFAOYSA-N 0.000 description 1
- ZZSLZQUPYGQPNA-UHFFFAOYSA-N 5,5-dimethylthieno[3,2-b]pyran-2-carbonitrile Chemical compound C1=CC(C)(C)OC2=C1SC(C#N)=C2 ZZSLZQUPYGQPNA-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- PYRMXWDZLODRCH-PWSUYJOCSA-N CC1([C@H]([C@@H](C2=C(O1)C=C(S2)C(=O)O)N2C(CCC2)=O)O)C Chemical compound CC1([C@H]([C@@H](C2=C(O1)C=C(S2)C(=O)O)N2C(CCC2)=O)O)C PYRMXWDZLODRCH-PWSUYJOCSA-N 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 239000005046 Chlorosilane Substances 0.000 description 1
- TVZCRIROJQEVOT-CABCVRRESA-N Cromakalim Chemical compound N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-CABCVRRESA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- JJSCUXAFAJEQGB-QMMMGPOBSA-N [(1s)-1-isocyanatoethyl]benzene Chemical compound O=C=N[C@@H](C)C1=CC=CC=C1 JJSCUXAFAJEQGB-QMMMGPOBSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 150000001562 benzopyrans Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229950004210 cromakalim Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 239000002244 precipitate Substances 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
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HSNUIYJWTSJUMS-UHFFFAOYSA-N sodium;trimethyl(oxido)silane Chemical compound [Na+].C[Si](C)(C)[O-] HSNUIYJWTSJUMS-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DTCKWTYGYOJMAT-UHFFFAOYSA-N thieno[3,2-b]pyran-5-one Chemical compound O1C(=O)C=CC2=C1C=CS2 DTCKWTYGYOJMAT-UHFFFAOYSA-N 0.000 description 1
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 1
- 239000005052 trichlorosilane Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT157389 | 1989-06-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK317290A3 SK317290A3 (en) | 1995-10-11 |
| SK278012B6 true SK278012B6 (en) | 1995-10-11 |
Family
ID=3516340
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK3172-90A SK278012B6 (en) | 1989-06-27 | 1990-06-26 | Thienopyrane derivatives, method of their production and their use |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US5077307A (cs) |
| EP (1) | EP0405298B1 (cs) |
| KR (1) | KR910000743A (cs) |
| CN (1) | CN1025621C (cs) |
| AT (1) | ATE105559T1 (cs) |
| AU (1) | AU628995B2 (cs) |
| CA (1) | CA2019737A1 (cs) |
| CZ (1) | CZ280543B6 (cs) |
| DD (1) | DD295850A5 (cs) |
| DE (1) | DE59005666D1 (cs) |
| DK (1) | DK0405298T3 (cs) |
| ES (1) | ES2053015T3 (cs) |
| FI (1) | FI96312C (cs) |
| HR (1) | HRP940819A2 (cs) |
| HU (1) | HU204834B (cs) |
| IE (1) | IE63935B1 (cs) |
| IL (1) | IL94703A (cs) |
| LT (1) | LT3799B (cs) |
| LV (1) | LV10776A (cs) |
| MD (1) | MD121C2 (cs) |
| NO (1) | NO174423C (cs) |
| NZ (1) | NZ234084A (cs) |
| PT (1) | PT94487B (cs) |
| RU (1) | RU1833386C (cs) |
| SK (1) | SK278012B6 (cs) |
| UA (1) | UA15930A (cs) |
| YU (1) | YU124690A (cs) |
| ZA (1) | ZA904885B (cs) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ230711A (en) * | 1988-09-23 | 1990-10-26 | Ortho Pharma Corp | Substituted thienopyrans as antihypertensive agents |
| DE3925719A1 (de) * | 1989-08-03 | 1991-02-07 | Bayer Ag | Substituierte thienopyranone, verfahren zu ihrer herstellung und ihre verwendung zur bekaempfung von parasiten |
| NZ240933A (en) * | 1990-12-21 | 1993-05-26 | Ortho Pharma Corp | Preparing enantiomerically pure thienopyran derivatives |
| GB9909792D0 (en) * | 1998-12-04 | 1999-06-23 | Cambridge Bioclinical Limited | Potassium channel activators and their use |
| MD149Z5 (ro) * | 2009-09-17 | 2010-09-30 | Сергей Чербарь | Sigiliu cu fibre optice din polimer |
| MD4034C2 (ro) * | 2009-11-03 | 2010-11-30 | Сергей Чербарь | Sigiliu indicator pentru dispozitive metrologice |
| MD4230C1 (ro) * | 2012-11-29 | 2013-12-31 | Фёдор СЫРБУ | Sigiliu |
| MD861Z (ro) * | 2014-06-03 | 2015-07-31 | Александр КОРЕНКОВ | Sigiliu |
| MD4534C1 (ro) * | 2017-03-03 | 2018-06-30 | Сергей Чербарь | Sigiliu cu rotor blocabil pentru dispozitive metrologice |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3274350D1 (en) * | 1981-09-25 | 1987-01-08 | Beecham Group Plc | Pharmaceutically active benzopyran compounds |
| GB8308062D0 (en) * | 1983-03-24 | 1983-05-05 | Beecham Group Plc | Active compounds |
| DE3682331D1 (de) * | 1985-06-08 | 1991-12-12 | Beecham Group Plc | Pyrano(3,2-c)pyridinderivate, verfahren und zwischenprodukte zu ihrer herstellung und diese enthaltende pharmazeutische zubereitungen. |
| GB8613786D0 (en) * | 1986-06-06 | 1986-07-09 | Beecham Group Plc | Active compounds |
| DE3881714D1 (de) * | 1987-02-04 | 1993-07-22 | Hoechst Ag | Alkylsubstituierte n-benzopyranyllactame, verfahren zu ihrer herstellung, ihre verwendung sowie pharmazeutische praeparate auf basis dieser verbindungen. |
| US4789525A (en) * | 1987-06-22 | 1988-12-06 | Eastman Kodak Company | Analytical method and multilayer element for total ionic iron determination |
| NZ230711A (en) * | 1988-09-23 | 1990-10-26 | Ortho Pharma Corp | Substituted thienopyrans as antihypertensive agents |
-
1990
- 1990-06-11 IE IE209790A patent/IE63935B1/en not_active IP Right Cessation
- 1990-06-12 IL IL9470390A patent/IL94703A/en not_active IP Right Cessation
- 1990-06-13 US US07/537,629 patent/US5077307A/en not_active Expired - Fee Related
- 1990-06-15 NZ NZ234084A patent/NZ234084A/en unknown
- 1990-06-19 DK DK90111529.5T patent/DK0405298T3/da not_active Application Discontinuation
- 1990-06-19 DE DE59005666T patent/DE59005666D1/de not_active Expired - Fee Related
- 1990-06-19 EP EP90111529A patent/EP0405298B1/de not_active Expired - Lifetime
- 1990-06-19 AT AT9090111529T patent/ATE105559T1/de not_active IP Right Cessation
- 1990-06-19 ES ES90111529T patent/ES2053015T3/es not_active Expired - Lifetime
- 1990-06-22 ZA ZA904885A patent/ZA904885B/xx unknown
- 1990-06-22 AU AU57787/90A patent/AU628995B2/en not_active Ceased
- 1990-06-23 KR KR1019900009322A patent/KR910000743A/ko not_active Ceased
- 1990-06-25 FI FI903172A patent/FI96312C/fi not_active IP Right Cessation
- 1990-06-25 CA CA002019737A patent/CA2019737A1/en not_active Abandoned
- 1990-06-25 PT PT94487A patent/PT94487B/pt not_active IP Right Cessation
- 1990-06-26 CZ CS903172A patent/CZ280543B6/cs unknown
- 1990-06-26 UA UA4830828A patent/UA15930A/uk unknown
- 1990-06-26 NO NO902832A patent/NO174423C/no unknown
- 1990-06-26 DD DD90342098A patent/DD295850A5/de not_active IP Right Cessation
- 1990-06-26 RU SU904830828A patent/RU1833386C/ru active
- 1990-06-26 YU YU01246/90A patent/YU124690A/xx unknown
- 1990-06-26 SK SK3172-90A patent/SK278012B6/sk unknown
- 1990-06-26 HU HU903998A patent/HU204834B/hu not_active IP Right Cessation
- 1990-06-27 CN CN90103312A patent/CN1025621C/zh not_active Expired - Fee Related
-
1993
- 1993-11-17 LV LV931243A patent/LV10776A/xx unknown
- 1993-12-14 LT LTIP1590A patent/LT3799B/lt not_active IP Right Cessation
-
1994
- 1994-05-24 MD MD94-0124A patent/MD121C2/ro not_active IP Right Cessation
- 1994-10-27 HR HRP-1246/90A patent/HRP940819A2/xx not_active Application Discontinuation
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