DE2134880C3 - Thieno-pyrimidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel - Google Patents
Thieno-pyrimidine, Verfahren zu ihrer Herstellung und diese enthaltende ArzneimittelInfo
- Publication number
- DE2134880C3 DE2134880C3 DE2134880A DE2134880A DE2134880C3 DE 2134880 C3 DE2134880 C3 DE 2134880C3 DE 2134880 A DE2134880 A DE 2134880A DE 2134880 A DE2134880 A DE 2134880A DE 2134880 C3 DE2134880 C3 DE 2134880C3
- Authority
- DE
- Germany
- Prior art keywords
- thieno
- pyrimidine
- amino
- hydroxy
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000002360 preparation method Methods 0.000 title claims description 18
- 238000000034 method Methods 0.000 title claims description 11
- 239000003814 drug Substances 0.000 title description 3
- -1 Ci -CV-alkylamino Chemical group 0.000 claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 34
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 13
- 239000003513 alkali Substances 0.000 claims description 11
- KQWHKLZRDFJOCN-UHFFFAOYSA-N thieno[3,4-d]pyrimidine Chemical class N1=CN=CC2=CSC=C21 KQWHKLZRDFJOCN-UHFFFAOYSA-N 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 10
- 241000251730 Chondrichthyes Species 0.000 claims description 8
- SCFLDALNYFZRIK-UHFFFAOYSA-N 2-chloro-n-propan-2-ylthieno[3,4-d]pyrimidin-4-amine Chemical compound CC(C)NC1=NC(Cl)=NC2=CSC=C12 SCFLDALNYFZRIK-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- MVKBLIGBWKCBCN-UHFFFAOYSA-N 2-ethoxy-n-propan-2-ylthieno[3,4-d]pyrimidin-4-amine Chemical compound N1=C(OCC)N=C(NC(C)C)C2=CSC=C21 MVKBLIGBWKCBCN-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- YMKICRAYPFSBSO-UHFFFAOYSA-N 2-ethoxy-n-propylthieno[3,4-d]pyrimidin-4-amine Chemical compound CCCNC1=NC(OCC)=NC2=CSC=C12 YMKICRAYPFSBSO-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 238000004458 analytical method Methods 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 22
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000012458 free base Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- FUFRGBBMQQJFMJ-UHFFFAOYSA-N 2,4-dichlorothieno[3,4-d]pyrimidine Chemical compound N1=C(Cl)N=C(Cl)C2=CSC=C21 FUFRGBBMQQJFMJ-UHFFFAOYSA-N 0.000 description 4
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 4
- 230000000747 cardiac effect Effects 0.000 description 4
- 229960000876 cinnarizine Drugs 0.000 description 4
- 229960001789 papaverine Drugs 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- XPJDJNLVKRNGPH-UHFFFAOYSA-N 2,4-diethoxythieno[3,4-d]pyrimidine Chemical compound N1=C(OCC)N=C(OCC)C2=CSC=C21 XPJDJNLVKRNGPH-UHFFFAOYSA-N 0.000 description 3
- WOYWLLHHWAMFCB-UHFFFAOYSA-N 2-ethylhexyl acetate Chemical compound CCCCC(CC)COC(C)=O WOYWLLHHWAMFCB-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940105994 ethylhexyl acetate Drugs 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CGYZVYDIFMJANQ-UHFFFAOYSA-N 2,4-dichloro-5-methylthieno[3,4-d]pyrimidine Chemical compound N1=C(Cl)N=C(Cl)C2=C(C)SC=C21 CGYZVYDIFMJANQ-UHFFFAOYSA-N 0.000 description 2
- BBHXNQPOHXENOJ-UHFFFAOYSA-N 4-(2-propylthieno[3,4-d]pyrimidin-4-yl)morpholine Chemical compound C12=CSC=C2N=C(CCC)N=C1N1CCOCC1 BBHXNQPOHXENOJ-UHFFFAOYSA-N 0.000 description 2
- OSMPALRXWMHPRD-UHFFFAOYSA-N 4-chloro-2-propylthieno[3,4-d]pyrimidine Chemical compound N1=C(CCC)N=C(Cl)C2=CSC=C21 OSMPALRXWMHPRD-UHFFFAOYSA-N 0.000 description 2
- WVFMXHMEFTVOIB-UHFFFAOYSA-N 4-n-propan-2-yl-2-n-propylthieno[3,4-d]pyrimidine-2,4-diamine Chemical compound N1=C(NCCC)N=C(NC(C)C)C2=CSC=C21 WVFMXHMEFTVOIB-UHFFFAOYSA-N 0.000 description 2
- UQOKZIGAHZYXLC-UHFFFAOYSA-N 5-methyl-1h-thieno[3,4-d]pyrimidine-2,4-dione Chemical compound N1=C(O)N=C(O)C2=C(C)SC=C21 UQOKZIGAHZYXLC-UHFFFAOYSA-N 0.000 description 2
- HPOLWWHVTZGREL-UHFFFAOYSA-N 5-methyl-4-n-propan-2-yl-2-n-propylthieno[3,4-d]pyrimidine-2,4-diamine Chemical compound N1=C(NCCC)N=C(NC(C)C)C2=C(C)SC=C21 HPOLWWHVTZGREL-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000002269 analeptic agent Substances 0.000 description 2
- 230000003555 analeptic effect Effects 0.000 description 2
- AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- TXAMOCHUEGHJML-UHFFFAOYSA-N ethyl 4-(carbamoylamino)-2-methylthiophene-3-carboxylate Chemical compound CCOC(=O)C1=C(C)SC=C1NC(N)=O TXAMOCHUEGHJML-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- MDFGIHMUKUHJMU-UHFFFAOYSA-N n-propan-2-ylthieno[3,4-d]pyrimidin-4-amine Chemical compound CC(C)NC1=NC=NC2=CSC=C12 MDFGIHMUKUHJMU-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- RZBNSEBSVPLRMA-UHFFFAOYSA-N 1h-thieno[3,4-d]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)NC2=CSC=C21 RZBNSEBSVPLRMA-UHFFFAOYSA-N 0.000 description 1
- BJRNUJIZPAWECC-UHFFFAOYSA-N 2-[[2-(propylamino)thieno[3,4-d]pyrimidin-4-yl]amino]propan-1-ol Chemical compound N1=C(NCCC)N=C(NC(C)CO)C2=CSC=C21 BJRNUJIZPAWECC-UHFFFAOYSA-N 0.000 description 1
- QVALAQMFPSQTKC-UHFFFAOYSA-N 2-chloro-4-(4-methylpiperazin-1-yl)thieno[3,4-d]pyrimidine Chemical compound C1CN(C)CCN1C1=NC(Cl)=NC2=CSC=C12 QVALAQMFPSQTKC-UHFFFAOYSA-N 0.000 description 1
- VIYUSXOQFKQPHA-UHFFFAOYSA-N 2-chloro-4-ethoxythieno[3,4-d]pyrimidine Chemical compound CCOC1=NC(Cl)=NC2=CSC=C12 VIYUSXOQFKQPHA-UHFFFAOYSA-N 0.000 description 1
- FWVBZFSHNHEBBZ-UHFFFAOYSA-N 2-chloro-4-piperidin-1-ylthieno[3,4-d]pyrimidine Chemical compound C12=CSC=C2N=C(Cl)N=C1N1CCCCC1 FWVBZFSHNHEBBZ-UHFFFAOYSA-N 0.000 description 1
- HVIGWXABOAJNME-UHFFFAOYSA-N 2-chloro-5-methyl-n-propan-2-ylthieno[3,4-d]pyrimidin-4-amine Chemical compound CC(C)NC1=NC(Cl)=NC2=CSC(C)=C12 HVIGWXABOAJNME-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- NVWKEGBDSSBGTD-UHFFFAOYSA-N 2-n-ethyl-4-n-propan-2-ylthieno[3,4-d]pyrimidine-2,4-diamine Chemical compound N1=C(NCC)N=C(NC(C)C)C2=CSC=C21 NVWKEGBDSSBGTD-UHFFFAOYSA-N 0.000 description 1
- QIHFLAURTFZSEX-UHFFFAOYSA-N 2-propyl-1h-thieno[3,4-d]pyrimidin-4-one Chemical compound N1=C(CCC)N=C(O)C2=CSC=C21 QIHFLAURTFZSEX-UHFFFAOYSA-N 0.000 description 1
- NZMMPTGEFNSVBC-UHFFFAOYSA-N 4-(2-chlorothieno[3,4-d]pyrimidin-4-yl)morpholine Chemical compound C12=CSC=C2N=C(Cl)N=C1N1CCOCC1 NZMMPTGEFNSVBC-UHFFFAOYSA-N 0.000 description 1
- HORWNRQRCWWONX-UHFFFAOYSA-N 4-[2-(4-methylpiperazin-1-yl)thieno[3,4-d]pyrimidin-4-yl]morpholine Chemical compound C1CN(C)CCN1C1=NC2=CSC=C2C(N2CCOCC2)=N1 HORWNRQRCWWONX-UHFFFAOYSA-N 0.000 description 1
- UGFJGBOOHQSNBQ-UHFFFAOYSA-N 4-n-butan-2-yl-2-n-propylthieno[3,4-d]pyrimidine-2,4-diamine Chemical compound N1=C(NCCC)N=C(NC(C)CC)C2=CSC=C21 UGFJGBOOHQSNBQ-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 240000007049 Juglans regia Species 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PGBFYLVIMDQYMS-UHFFFAOYSA-N Methyl thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=CS1 PGBFYLVIMDQYMS-UHFFFAOYSA-N 0.000 description 1
- WMJIFLXGECCUNM-UHFFFAOYSA-N N1(CCCC1)C1N(CCOC1)N1CCCCC1 Chemical compound N1(CCCC1)C1N(CCOC1)N1CCCCC1 WMJIFLXGECCUNM-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 125000004122 cyclic group Chemical class 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- OBSIYBMTDOHLNJ-UHFFFAOYSA-N ethyl 2-methyl-4-oxothiolane-3-carboxylate Chemical compound CCOC(=O)C1C(C)SCC1=O OBSIYBMTDOHLNJ-UHFFFAOYSA-N 0.000 description 1
- JFGSHIFFUDQQOJ-UHFFFAOYSA-N ethyl 4-amino-2-methylthiophene-3-carboxylate Chemical compound CCOC(=O)C1=C(C)SC=C1N JFGSHIFFUDQQOJ-UHFFFAOYSA-N 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 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
- 238000012812 general test Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- RBBOWEDMXHTEPA-UHFFFAOYSA-N hexane;toluene Chemical compound CCCCCC.CC1=CC=CC=C1 RBBOWEDMXHTEPA-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- LROFLRPIPNWJJG-UHFFFAOYSA-N methyl 4-(butanoylamino)thiophene-3-carboxylate Chemical compound CCCC(=O)NC1=CSC=C1C(=O)OC LROFLRPIPNWJJG-UHFFFAOYSA-N 0.000 description 1
- BUFZZXCVOFBHLS-UHFFFAOYSA-N methyl 4-aminothiophene-3-carboxylate Chemical compound COC(=O)C1=CSC=C1N BUFZZXCVOFBHLS-UHFFFAOYSA-N 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- VPIHOHZXGKTAOT-UHFFFAOYSA-N n-propan-2-yl-2-propylthieno[3,4-d]pyrimidin-4-amine Chemical compound N1=C(CCC)N=C(NC(C)C)C2=CSC=C21 VPIHOHZXGKTAOT-UHFFFAOYSA-N 0.000 description 1
- 125000004888 n-propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- NCYVXEGFNDZQCU-UHFFFAOYSA-N nikethamide Chemical compound CCN(CC)C(=O)C1=CC=CN=C1 NCYVXEGFNDZQCU-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- VMXUWOKSQNHOCA-UKTHLTGXSA-N ranitidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-UKTHLTGXSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 1
- 238000002061 vacuum sublimation Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 210000002385 vertebral artery Anatomy 0.000 description 1
- 235000020234 walnut Nutrition 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pulmonology (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 |
|---|---|---|---|
| GB3414470 | 1970-07-14 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2134880A1 DE2134880A1 (de) | 1972-05-25 |
| DE2134880B2 DE2134880B2 (de) | 1977-12-15 |
| DE2134880C3 true DE2134880C3 (de) | 1978-08-31 |
Family
ID=10361935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2134880A Expired DE2134880C3 (de) | 1970-07-14 | 1971-07-13 | Thieno-pyrimidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US3850919A (enExample) |
| JP (2) | JPS5344476B1 (enExample) |
| BE (1) | BE769843A (enExample) |
| DE (1) | DE2134880C3 (enExample) |
| FR (1) | FR2100899B1 (enExample) |
| GB (1) | GB1324849A (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3931204A (en) * | 1971-07-13 | 1976-01-06 | U.C.B. Societe Anonyme | Thieno[3,4-d]pyrimidines |
| GB1570494A (en) * | 1975-11-28 | 1980-07-02 | Ici Ltd | Thienopyrimidine derivatives and their use as pesticides |
| JPS58152593U (ja) * | 1982-04-07 | 1983-10-12 | 三洋電機株式会社 | 遠隔操作式電気機器 |
| JPS5980171U (ja) * | 1982-11-24 | 1984-05-30 | ティー・シー・エム株式会社 | 荷役車両のボンネツト |
-
1970
- 1970-07-14 GB GB3414470A patent/GB1324849A/en not_active Expired
-
1971
- 1971-07-09 FR FR7125563A patent/FR2100899B1/fr not_active Expired
- 1971-07-12 BE BE769843A patent/BE769843A/xx not_active IP Right Cessation
- 1971-07-13 US US00162255A patent/US3850919A/en not_active Expired - Lifetime
- 1971-07-13 DE DE2134880A patent/DE2134880C3/de not_active Expired
- 1971-07-13 JP JP5206171A patent/JPS5344476B1/ja active Pending
-
1978
- 1978-03-24 JP JP3399178A patent/JPS53124291A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5748118B2 (enExample) | 1982-10-14 |
| GB1324849A (en) | 1973-07-25 |
| BE769843A (fr) | 1972-01-12 |
| DE2134880B2 (de) | 1977-12-15 |
| US3850919A (en) | 1974-11-26 |
| JPS53124291A (en) | 1978-10-30 |
| FR2100899A1 (enExample) | 1972-03-24 |
| DE2134880A1 (de) | 1972-05-25 |
| FR2100899B1 (enExample) | 1974-11-15 |
| JPS5344476B1 (enExample) | 1978-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0005205B1 (de) | Substituierte 5,6-Dimethylpyrrolo(2,3-d)pyrimidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
| DE69014351T2 (de) | Pyridincarbonsäureamid-Derivate und diese enthaltende pharmazeutische Zusammensetzungen. | |
| DE1795769B2 (de) | 6,7A9-Tetrahydro-2H-pyrido [1,2-a] pyrimidinderivate, deren Salze mit Säuren und quaternär? Methosalze, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende Arzneimittel | |
| CH625522A5 (enExample) | ||
| DE2120495A1 (de) | Neue Trialkoxychinazolin-Verbindungen und Verfahren zu ihrer Herstellung | |
| DE3779825T2 (de) | Derivate von benzhydryloxyaethylpiperazinen, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zusammensetzungen. | |
| DE3430284A1 (de) | Neue tryptamin-derivate, ein verfahren zu ihrer herstellung und ihre verwendung | |
| DE2149249A1 (de) | 6-Arylpyrimidine | |
| DD263772A5 (de) | Verfahren zur herstellung neuer 1h, 3h-pyrrolo[1,2-c]thiazolderivate | |
| DE2727469A1 (de) | Neue hexahydropyrimidine, verfahren zu ihrer herstellung und arzneimittel, die diese verbindungen enthalten | |
| DE2461802A1 (de) | Pyrazinderivate | |
| DE2134880C3 (de) | Thieno-pyrimidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
| DE3782636T2 (de) | Isoindolin-1-on-derivat und antiarrhythmisches mittel. | |
| DE3013906A1 (de) | Substituierte (alpha) -aminocarbonyl-l-benzyl-3,4-dihydro-isochinoline, verfahren zu deren herstellung und deren verwendung | |
| DD216014A5 (de) | Verfahren zur herstellung von verbindungen mit einem heterocyclischen distickstoffkern | |
| DE3888215T2 (de) | Piperazinylpyrimidine als beta-adrenergische Rezeptoren blockierende Mittel. | |
| DD202563A5 (de) | Verfahren zur herstellung von 1,5-diphenylpyrazolin-3-on-verbindungen | |
| DD210040A5 (de) | Verfahren zur herstellung von 4-phenyl-chinazolin-derivaten | |
| DE2457309A1 (de) | 2-phenylhydrazinothiazolin- beziehungsweise 2-phenylhydrazinothiazininderivate sowie ihre verwendung und verfahren zur herstellung derselben | |
| DE2819896A1 (de) | Chromenderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel | |
| DE2046577A1 (de) | Neue Pyrimidopyndazinderivate und Verfahren zu ihrer Herstellung | |
| EP0004904B1 (de) | 2-Amino-3a,4,5,6-tetrahydro-perimidin-Derivate, diese enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
| DE2051961A1 (de) | 6 substituierte Indol eckige Klammer auf 1,2 c eckige Klammer zu chinazoline und Verfahren zu deren Herstellung | |
| DE69429569T2 (de) | Bis(hydroxymethyl)cyclopropylmethyl Pyrimidin Derivate, deren Herstellung und deren Verwendung als anti-virale Mittel | |
| DE68921470T2 (de) | Diazabicycloalkan-derivate. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| 8339 | Ceased/non-payment of the annual fee |