CA1176247A - Trisubstituted pyrimido [5,4-d] pyrimidines, their preparation and their use as pharmaceuticals - Google Patents
Trisubstituted pyrimido [5,4-d] pyrimidines, their preparation and their use as pharmaceuticalsInfo
- Publication number
- CA1176247A CA1176247A CA000393091A CA393091A CA1176247A CA 1176247 A CA1176247 A CA 1176247A CA 000393091 A CA000393091 A CA 000393091A CA 393091 A CA393091 A CA 393091A CA 1176247 A CA1176247 A CA 1176247A
- Authority
- CA
- Canada
- Prior art keywords
- group
- carbon atoms
- groups
- alkyl
- optionally substituted
- 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 15
- JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 title abstract 2
- 239000003814 drug Substances 0.000 title description 2
- -1 hydroxy, mercapto Chemical class 0.000 claims abstract description 264
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
- 239000002253 acid Substances 0.000 claims abstract description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000003277 amino group Chemical class 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 210
- 125000000217 alkyl group Chemical group 0.000 claims description 114
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 73
- 150000001875 compounds Chemical class 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 125000003545 alkoxy group Chemical group 0.000 claims description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000004414 alkyl thio group Chemical group 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 14
- 125000002425 furfuryl group Chemical group C(C1=CC=CO1)* 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
- 230000003647 oxidation Effects 0.000 claims description 10
- 238000007254 oxidation reaction Methods 0.000 claims description 10
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000011737 fluorine Chemical group 0.000 claims description 9
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 9
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 7
- 239000007800 oxidant agent Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 230000000269 nucleophilic effect Effects 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Chemical group 0.000 claims description 3
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- KAIRAEWLMZMXEL-UHFFFAOYSA-N 2-[[8-(benzylamino)-4-(1-oxo-1,4-thiazinan-4-yl)pyrimido[5,4-d]pyrimidin-2-yl]amino]ethanol Chemical compound C=12N=CN=C(NCC=3C=CC=CC=3)C2=NC(NCCO)=NC=1N1CCS(=O)CC1 KAIRAEWLMZMXEL-UHFFFAOYSA-N 0.000 claims description 2
- 229910001508 alkali metal halide Inorganic materials 0.000 claims description 2
- 150000008045 alkali metal halides Chemical class 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000004803 chlorobenzyl group Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 125000006502 nitrobenzyl group Chemical group 0.000 claims description 2
- 150000007530 organic bases Chemical group 0.000 claims description 2
- 235000013350 formula milk Nutrition 0.000 claims 32
- 238000004519 manufacturing process Methods 0.000 claims 4
- MYEUKQVEDDDHKN-UHFFFAOYSA-N 2-[[8-benzylsulfanyl-4-(1-oxo-1,4-thiazinan-4-yl)pyrimido[5,4-d]pyrimidin-2-yl]amino]ethanol Chemical compound C=12N=CN=C(SCC=3C=CC=CC=3)C2=NC(NCCO)=NC=1N1CCS(=O)CC1 MYEUKQVEDDDHKN-UHFFFAOYSA-N 0.000 claims 2
- 125000005237 alkyleneamino group Chemical group 0.000 claims 2
- 230000001590 oxidative effect Effects 0.000 claims 2
- UNHJBCCKHKDXOC-UHFFFAOYSA-N 2-[(8-benzylsulfanyl-4-thiomorpholin-4-ylpyrimido[5,4-d]pyrimidin-2-yl)amino]ethanol Chemical compound C=12N=CN=C(SCC=3C=CC=CC=3)C2=NC(NCCO)=NC=1N1CCSCC1 UNHJBCCKHKDXOC-UHFFFAOYSA-N 0.000 claims 1
- BAWWKDNLEZZFSS-UHFFFAOYSA-N 4-(8-benzylsulfanyl-2-chloropyrimido[5,4-d]pyrimidin-4-yl)-1,4-thiazinane 1-oxide Chemical compound C=12N=CN=C(SCC=3C=CC=CC=3)C2=NC(Cl)=NC=1N1CCS(=O)CC1 BAWWKDNLEZZFSS-UHFFFAOYSA-N 0.000 claims 1
- 125000006178 methyl benzyl group Chemical group 0.000 claims 1
- IYHKZYBVJJPGFD-UHFFFAOYSA-N n-benzyl-2-chloro-4-(1-oxo-1,4-thiazinan-4-yl)pyrimido[5,4-d]pyrimidin-8-amine Chemical compound C=12N=CN=C(NCC=3C=CC=CC=3)C2=NC(Cl)=NC=1N1CCS(=O)CC1 IYHKZYBVJJPGFD-UHFFFAOYSA-N 0.000 claims 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 230000002785 anti-thrombosis Effects 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 125000004122 cyclic group Chemical group 0.000 abstract 2
- 125000001841 imino group Chemical group [H]N=* 0.000 abstract 2
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 2
- 238000002844 melting Methods 0.000 description 333
- 230000008018 melting Effects 0.000 description 332
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 207
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 187
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 155
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 147
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 43
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 235000011167 hydrochloric acid Nutrition 0.000 description 10
- 229960000443 hydrochloric acid Drugs 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000013543 active substance Substances 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000000155 melt Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000001226 reprecipitation Methods 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 241001024304 Mino Species 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- FRGGNTDUBQNZBA-UHFFFAOYSA-N 2-(2-methoxyethylamino)ethanol Chemical compound COCCNCCO FRGGNTDUBQNZBA-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000012286 potassium permanganate Substances 0.000 description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- GIAFURWZWWWBQT-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanol Chemical compound NCCOCCO GIAFURWZWWWBQT-UHFFFAOYSA-N 0.000 description 2
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- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 206010027476 Metastases Diseases 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 208000001435 Thromboembolism Diseases 0.000 description 2
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- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 229940116364 hard fat Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 125000000369 oxido group Chemical group [*]=O 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Luminescent Compositions (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3049207.0 | 1980-12-27 | ||
| DE19803049207 DE3049207A1 (de) | 1980-12-27 | 1980-12-27 | Neue trisubstituierte pyrimido (5,4-d) pyrimidine, ihre herstellung und ihre verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1176247A true CA1176247A (en) | 1984-10-16 |
Family
ID=6120399
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000393091A Expired CA1176247A (en) | 1980-12-27 | 1981-12-23 | Trisubstituted pyrimido [5,4-d] pyrimidines, their preparation and their use as pharmaceuticals |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4478833A (en, 2012) |
| EP (1) | EP0055444B1 (en, 2012) |
| JP (1) | JPS57134485A (en, 2012) |
| AT (1) | ATE12232T1 (en, 2012) |
| AU (1) | AU547792B2 (en, 2012) |
| CA (1) | CA1176247A (en, 2012) |
| DE (2) | DE3049207A1 (en, 2012) |
| DK (1) | DK548981A (en, 2012) |
| ES (1) | ES508343A0 (en, 2012) |
| FI (1) | FI71151C (en, 2012) |
| GB (1) | GB2090833B (en, 2012) |
| GR (1) | GR76356B (en, 2012) |
| IE (1) | IE52323B1 (en, 2012) |
| IL (1) | IL64647A (en, 2012) |
| NO (1) | NO158256C (en, 2012) |
| NZ (1) | NZ199376A (en, 2012) |
| PH (1) | PH22243A (en, 2012) |
| PT (1) | PT74199B (en, 2012) |
| ZA (1) | ZA818934B (en, 2012) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3423092A1 (de) * | 1984-06-22 | 1986-01-02 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue 8-alkylthio-2-piperazino-pyrimido(5,4-d) pyrimidine, ihre herstellung und diese verbindungen enthaltende arzneimittel |
| JPH075594B2 (ja) * | 1986-03-25 | 1995-01-25 | 三井石油化学工業株式会社 | 新規ピリドピリミジン誘導体 |
| DE3631294A1 (de) * | 1986-09-13 | 1988-03-24 | Thomae Gmbh Dr K | Neue synergistische kombination bestehend aus einem phosphodiesterase-hemmer und einem thromboxan-a(pfeil abwaerts)2(pfeil abwaerts)-antagonisten und deren verwendung bzw. herstellung |
| DE4325900A1 (de) * | 1993-08-02 | 1995-02-09 | Thomae Gmbh Dr K | Trisubstituierte Pyrimido [5,4-d] pyrimidine zur Modulation der Multidrugresistenz, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
| DE19608588A1 (de) * | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido [5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19608653A1 (de) * | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| US8309562B2 (en) * | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| CA2531327A1 (en) | 2003-07-03 | 2005-01-13 | Myriad Genetics, Inc. | Compounds and therapeutical use thereof |
| DE102004002557A1 (de) * | 2004-01-17 | 2005-08-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von substituierten Pyrimido(5,4-d)pyrimidinen zur Behandlung von Atemwegserkrankungen |
| AU2005275935A1 (en) * | 2004-08-24 | 2006-03-02 | Sumitomo Chemical Company, Limited | Method for producing 2-(4-methyl-2-phenylpiperazine-1-yl)-3-cyanopiridine |
| EP1833482A4 (en) | 2005-01-03 | 2011-02-16 | Myriad Genetics Inc | COMPOUNDS AND ITS THERAPEUTIC USE |
| US8258145B2 (en) * | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB807826A (en) * | 1955-03-14 | 1959-01-21 | Thomae Gmbh Dr K | Derivatives of pyrimido[5,4-d] pyrimidine and production thereof |
| DE1150086B (de) * | 1956-04-25 | 1963-06-12 | Thomae Gmbh Dr K | Verfahren zur Herstellung von 2-Morpholino-4, 8-bis-(3'-methoxy-propylamino)-pyrimido [5, 4-d] pyrimidin |
| US3031450A (en) * | 1959-04-30 | 1962-04-24 | Thomae Gmbh Dr K | Substituted pyrimido-[5, 4-d]-pyrimidines |
| DE1168439B (de) * | 1959-06-25 | 1964-04-23 | Thomae Gmbh Dr K | Verfahren zur Herstellung von Estern von Hydroxyalkylamino-pyrimido [5, 4-d] pyrimidinen |
| FR1292943A (fr) * | 1960-04-27 | 1962-05-11 | Thomae Gmbh Dr K | Procédé pour la fabrication de dérivés de la pyrimido-[5, 4-d]-pyrimidine |
| GB1051218A (en, 2012) * | 1963-03-09 | |||
| US3322755A (en) * | 1964-03-10 | 1967-05-30 | Boehringer Sohn Ingelheim | Basic-substituted 1, 2, 3, 4-tetrahydropyrimido [5, 4-d]-pyrimidines |
| DE3069211D1 (en) * | 1979-07-03 | 1984-10-25 | Thomae Gmbh Dr K | 2-(perhydro-1,4-diazino)-pyrimido(5,4-d)pyrimidines, their preparation and medicaments containing them |
-
1980
- 1980-12-27 DE DE19803049207 patent/DE3049207A1/de not_active Withdrawn
-
1981
- 1981-12-10 GR GR66769A patent/GR76356B/el unknown
- 1981-12-10 DK DK548981A patent/DK548981A/da not_active Application Discontinuation
- 1981-12-16 NO NO814299A patent/NO158256C/no unknown
- 1981-12-16 US US06/331,285 patent/US4478833A/en not_active Expired - Fee Related
- 1981-12-21 DE DE8181110635T patent/DE3169480D1/de not_active Expired
- 1981-12-21 EP EP81110635A patent/EP0055444B1/de not_active Expired
- 1981-12-21 AT AT81110635T patent/ATE12232T1/de not_active IP Right Cessation
- 1981-12-23 IE IE3078/81A patent/IE52323B1/en unknown
- 1981-12-23 FI FI814148A patent/FI71151C/fi not_active IP Right Cessation
- 1981-12-23 NZ NZ199376A patent/NZ199376A/en unknown
- 1981-12-23 CA CA000393091A patent/CA1176247A/en not_active Expired
- 1981-12-23 PT PT74199A patent/PT74199B/pt unknown
- 1981-12-23 PH PH26758A patent/PH22243A/en unknown
- 1981-12-24 GB GB8138963A patent/GB2090833B/en not_active Expired
- 1981-12-24 AU AU79041/81A patent/AU547792B2/en not_active Ceased
- 1981-12-24 ES ES508343A patent/ES508343A0/es active Granted
- 1981-12-25 JP JP56216100A patent/JPS57134485A/ja active Pending
- 1981-12-25 IL IL64647A patent/IL64647A/xx unknown
- 1981-12-28 ZA ZA818934A patent/ZA818934B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FI71151C (fi) | 1986-11-24 |
| IL64647A (en) | 1985-10-31 |
| FI71151B (fi) | 1986-08-14 |
| IE813078L (en) | 1982-06-27 |
| NZ199376A (en) | 1985-12-13 |
| ES8300768A1 (es) | 1982-11-01 |
| AU7904181A (en) | 1982-07-08 |
| GR76356B (en, 2012) | 1984-08-06 |
| GB2090833A (en) | 1982-07-21 |
| IL64647A0 (en) | 1982-03-31 |
| ZA818934B (en) | 1983-09-28 |
| EP0055444A3 (en) | 1982-08-04 |
| EP0055444B1 (de) | 1985-03-20 |
| NO158256C (no) | 1988-08-10 |
| FI814148L (fi) | 1982-06-28 |
| JPS57134485A (en) | 1982-08-19 |
| AU547792B2 (en) | 1985-11-07 |
| GB2090833B (en) | 1984-10-31 |
| ES508343A0 (es) | 1982-11-01 |
| US4478833A (en) | 1984-10-23 |
| EP0055444A2 (de) | 1982-07-07 |
| DE3169480D1 (en) | 1985-04-25 |
| DE3049207A1 (de) | 1982-07-29 |
| NO814299L (no) | 1982-06-28 |
| PT74199B (de) | 1984-01-05 |
| DK548981A (da) | 1982-06-28 |
| NO158256B (no) | 1988-05-02 |
| PT74199A (de) | 1982-01-01 |
| ATE12232T1 (de) | 1985-04-15 |
| PH22243A (en) | 1988-07-01 |
| IE52323B1 (en) | 1987-09-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEC | Expiry (correction) | ||
| MKEX | Expiry |