CA1291757C - Pyrimidine derivatives - Google Patents
Pyrimidine derivativesInfo
- Publication number
- CA1291757C CA1291757C CA000543812A CA543812A CA1291757C CA 1291757 C CA1291757 C CA 1291757C CA 000543812 A CA000543812 A CA 000543812A CA 543812 A CA543812 A CA 543812A CA 1291757 C CA1291757 C CA 1291757C
- Authority
- CA
- Canada
- Prior art keywords
- pyrimidine
- pyrazolyl
- imidazolyl
- group
- chloro
- 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 - Lifetime
Links
- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 7
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 46
- -1 1-pyrazolyl Chemical group 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 30
- 230000000767 anti-ulcer Effects 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 8
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 3
- ZSXAXULNRYCRRQ-UHFFFAOYSA-N 4-ethoxy-6-methyl-2-pyrazol-1-ylpyrimidine Chemical compound CCOC1=CC(C)=NC(N2N=CC=C2)=N1 ZSXAXULNRYCRRQ-UHFFFAOYSA-N 0.000 claims description 2
- JMOIYFQXFXBKRH-UHFFFAOYSA-N 4-methoxy-6-methyl-2-pyrazol-1-ylpyrimidine Chemical compound COC1=CC(C)=NC(N2N=CC=C2)=N1 JMOIYFQXFXBKRH-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- NNSVPSHGALYRGV-UHFFFAOYSA-N ClC1=CC(=NC=N1)N1N=CC=C1.N1(C=NC=C1)C1=NC=CC(=N1)N1C=NC=C1.N1(N=CC=C1)C1=NC=CC(=N1)N1N=CC=C1.N1(C=NC=C1)C1=NC=NC(=C1)N1C=NC=C1.N1(N=CC=C1)C1=NC=NC(=C1)N1N=CC=C1 Chemical compound ClC1=CC(=NC=N1)N1N=CC=C1.N1(C=NC=C1)C1=NC=CC(=N1)N1C=NC=C1.N1(N=CC=C1)C1=NC=CC(=N1)N1N=CC=C1.N1(C=NC=C1)C1=NC=NC(=C1)N1C=NC=C1.N1(N=CC=C1)C1=NC=NC(=C1)N1N=CC=C1 NNSVPSHGALYRGV-UHFFFAOYSA-N 0.000 claims 1
- CSJAONIZIXJJTF-UHFFFAOYSA-N O(C1=CC=CC=C1)C1=CC(=NC=N1)N1N=CC=C1.NC1=CC(=NC=N1)N1N=CC=C1.N1(CCCCC1)C1=CC(=NC=N1)N1N=CC=C1.N1(C=NC=C1)C1=NC=CC(=N1)OC.C(C)(C)OC1=CC(=NC=N1)N1N=CC=C1 Chemical compound O(C1=CC=CC=C1)C1=CC(=NC=N1)N1N=CC=C1.NC1=CC(=NC=N1)N1N=CC=C1.N1(CCCCC1)C1=CC(=NC=N1)N1N=CC=C1.N1(C=NC=C1)C1=NC=CC(=N1)OC.C(C)(C)OC1=CC(=NC=N1)N1N=CC=C1 CSJAONIZIXJJTF-UHFFFAOYSA-N 0.000 claims 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 abstract description 7
- 125000002883 imidazolyl group Chemical group 0.000 abstract description 6
- 125000001425 triazolyl group Chemical group 0.000 abstract description 6
- 125000004104 aryloxy group Chemical group 0.000 abstract description 4
- 208000008469 Peptic Ulcer Diseases 0.000 abstract description 3
- 208000011906 peptic ulcer disease Diseases 0.000 abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 238000000034 method Methods 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 101150041968 CDC13 gene Proteins 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- ITORZLJASZQARK-UHFFFAOYSA-N 4,6-di(pyrazol-1-yl)pyrimidine Chemical compound C1=CC=NN1C1=CC(N2N=CC=C2)=NC=N1 ITORZLJASZQARK-UHFFFAOYSA-N 0.000 description 5
- HDRFFLHBLUPAKE-UHFFFAOYSA-N 4-chloro-6-pyrazol-1-ylpyrimidine Chemical compound C1=NC(Cl)=CC(N2N=CC=C2)=N1 HDRFFLHBLUPAKE-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 210000002784 stomach Anatomy 0.000 description 5
- 150000003852 triazoles Chemical class 0.000 description 5
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 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 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- HBGCZKKCKKDPOI-UHFFFAOYSA-N 2-chloro-4-methoxy-6-methylpyrimidine Chemical compound COC1=CC(C)=NC(Cl)=N1 HBGCZKKCKKDPOI-UHFFFAOYSA-N 0.000 description 3
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000007080 aromatic substitution reaction Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- DWNKNOSIDWJEBZ-UHFFFAOYSA-N 2,4-di(imidazol-1-yl)pyrimidine Chemical compound C1=NC=CN1C1=CC=NC(N2C=NC=C2)=N1 DWNKNOSIDWJEBZ-UHFFFAOYSA-N 0.000 description 2
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 2
- VEGXTHMAVSWQTH-UHFFFAOYSA-N 2-chloro-4-ethoxy-6-methylpyrimidine Chemical compound CCOC1=CC(C)=NC(Cl)=N1 VEGXTHMAVSWQTH-UHFFFAOYSA-N 0.000 description 2
- DCQGLKJULMYXAV-UHFFFAOYSA-N 4-chloro-2-imidazol-1-ylpyrimidine Chemical compound ClC1=CC=NC(N2C=NC=C2)=N1 DCQGLKJULMYXAV-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000002467 anti-pepsin effect Effects 0.000 description 2
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- 238000004440 column chromatography Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229960004592 isopropanol Drugs 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 238000013222 sprague-dawley male rat Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- AJNAMVHKXSFJFJ-UHFFFAOYSA-N 2-chloro-4-imidazol-1-ylpyrimidine Chemical compound ClC1=NC=CC(N2C=NC=C2)=N1 AJNAMVHKXSFJFJ-UHFFFAOYSA-N 0.000 description 1
- AONCLSDFPYXELL-UHFFFAOYSA-N 2-imidazol-1-yl-4-methoxy-6-methylpyrimidine Chemical compound COC1=CC(C)=NC(N2C=NC=C2)=N1 AONCLSDFPYXELL-UHFFFAOYSA-N 0.000 description 1
- MLTSBTVXGJSIOQ-UHFFFAOYSA-N 2-imidazol-1-yl-4-methoxypyrimidine Chemical compound COC1=CC=NC(N2C=NC=C2)=N1 MLTSBTVXGJSIOQ-UHFFFAOYSA-N 0.000 description 1
- HYNIJNUNVBFXNN-UHFFFAOYSA-N 2-methoxy-4-methyl-6-(1,2,4-triazol-1-yl)pyrimidine Chemical compound COC1=NC(C)=CC(N2N=CN=C2)=N1 HYNIJNUNVBFXNN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical class NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical class COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ONOSIHCSUIEICE-UHFFFAOYSA-N 4-chloro-2-methoxy-6-methylpyrimidine Chemical compound COC1=NC(C)=CC(Cl)=N1 ONOSIHCSUIEICE-UHFFFAOYSA-N 0.000 description 1
- BOBHIPMYQAROLL-UHFFFAOYSA-N 4-chloro-6-imidazol-1-ylpyrimidine Chemical compound C1=NC(Cl)=CC(N2C=NC=C2)=N1 BOBHIPMYQAROLL-UHFFFAOYSA-N 0.000 description 1
- GYWARUMEOXBMQX-UHFFFAOYSA-N 4-ethoxy-2-imidazol-1-yl-6-methylpyrimidine Chemical compound CCOC1=CC(C)=NC(N2C=NC=C2)=N1 GYWARUMEOXBMQX-UHFFFAOYSA-N 0.000 description 1
- JZJJPJWXORKLGK-UHFFFAOYSA-N 4-imidazol-1-yl-6-methoxypyrimidine Chemical compound C1=NC(OC)=CC(N2C=NC=C2)=N1 JZJJPJWXORKLGK-UHFFFAOYSA-N 0.000 description 1
- RECQJRLJPPRICN-UHFFFAOYSA-N 4-methoxy-6-pyrazol-1-ylpyrimidine Chemical compound C1=NC(OC)=CC(N2N=CC=C2)=N1 RECQJRLJPPRICN-UHFFFAOYSA-N 0.000 description 1
- OYMRGNAOABAKMM-UHFFFAOYSA-N 4-phenoxy-6-pyrazol-1-ylpyrimidine Chemical compound C=1C(N2N=CC=C2)=NC=NC=1OC1=CC=CC=C1 OYMRGNAOABAKMM-UHFFFAOYSA-N 0.000 description 1
- BUCREIZRYQPPRS-UHFFFAOYSA-N 4-piperidin-1-yl-6-pyrazol-1-ylpyrimidine Chemical compound C1CCCCN1C1=CC(N2N=CC=C2)=NC=N1 BUCREIZRYQPPRS-UHFFFAOYSA-N 0.000 description 1
- XYYWPIPDUIKOSX-UHFFFAOYSA-N 4-propan-2-yloxy-6-pyrazol-1-ylpyrimidine Chemical compound C1=NC(OC(C)C)=CC(N2N=CC=C2)=N1 XYYWPIPDUIKOSX-UHFFFAOYSA-N 0.000 description 1
- WAQXCJDLNSZZSS-UHFFFAOYSA-N 6-pyrazol-1-ylpyrimidin-4-amine Chemical compound C1=NC(N)=CC(N2N=CC=C2)=N1 WAQXCJDLNSZZSS-UHFFFAOYSA-N 0.000 description 1
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- 102100022210 COX assembly mitochondrial protein 2 homolog Human genes 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 101000900446 Homo sapiens COX assembly mitochondrial protein 2 homolog Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
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- 206010042220 Stress ulcer Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241001433070 Xiphoides Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002180 anti-stress Effects 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Chemical class 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 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 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000011975 tartaric acid Chemical class 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 210000002417 xiphoid bone Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61184484A JPS6339875A (ja) | 1986-08-05 | 1986-08-05 | ピリミジン誘導体 |
| JP61-184484 | 1986-08-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1291757C true CA1291757C (en) | 1991-11-05 |
Family
ID=16153982
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000543812A Expired - Lifetime CA1291757C (en) | 1986-08-05 | 1987-08-05 | Pyrimidine derivatives |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4849424A (en, 2012) |
| EP (1) | EP0257850B1 (en, 2012) |
| JP (1) | JPS6339875A (en, 2012) |
| CA (1) | CA1291757C (en, 2012) |
| DE (1) | DE3788385T2 (en, 2012) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0421266A1 (de) * | 1989-10-06 | 1991-04-10 | BASF Aktiengesellschaft | Azolylpyrimidin- und -triazinderivate und sie enthaltende Mittel |
| JPH0710859B2 (ja) * | 1990-05-10 | 1995-02-08 | 日清食品株式会社 | ビスアゾリルピリミジン誘導体の製造方法 |
| DE4131924A1 (de) * | 1991-09-25 | 1993-07-08 | Hoechst Ag | Substituierte 4-alkoxypyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel |
| US5318975A (en) * | 1993-02-16 | 1994-06-07 | Berlex Laboratories, Inc. | 5-pyrimdineamine derivatives |
| US6432947B1 (en) | 1997-02-19 | 2002-08-13 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as NOS inhibitors |
| DK0968206T3 (da) * | 1997-02-19 | 2007-03-26 | Berlex Inc | N-heterocykliske derivater som NOS-inhibitorer |
| US7037916B2 (en) | 1999-07-15 | 2006-05-02 | Pharmacopeia Drug Discovery, Inc. | Pyrimidine derivatives as IL-8 receptor antagonists |
| US6525051B2 (en) | 2000-03-27 | 2003-02-25 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| JP4186484B2 (ja) * | 2002-03-12 | 2008-11-26 | 住友化学株式会社 | ピリミジン化合物およびその用途 |
| US6982259B2 (en) | 2002-04-30 | 2006-01-03 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| US20050014753A1 (en) * | 2003-04-04 | 2005-01-20 | Irm Llc | Novel compounds and compositions as protein kinase inhibitors |
| CN100424083C (zh) * | 2006-10-14 | 2008-10-08 | 广西民族大学 | 一种嘧啶衍生化合物及其制备方法 |
| EP2417123A2 (en) | 2009-04-06 | 2012-02-15 | Agios Pharmaceuticals, Inc. | Therapeutic compositions and related methods of use |
| WO2010119879A1 (en) * | 2009-04-16 | 2010-10-21 | Sumitomo Chemical Company, Limited | Pyrimidine compound and its use for pest control |
| WO2010119878A1 (en) * | 2009-04-16 | 2010-10-21 | Sumitomo Chemical Company, Limited | Pyrimidine compound and its use for pest control |
| SG10201403696UA (en) | 2009-06-29 | 2014-10-30 | Agios Pharmaceuticals Inc | Therapeutic compounds and compositions |
| JP5764555B2 (ja) | 2009-06-29 | 2015-08-19 | アジオス ファーマシューティカルズ， インコーポレイテッド | 治療組成物および関連する使用方法 |
| ES2564952T3 (es) | 2010-12-17 | 2016-03-30 | Agios Pharmaceuticals, Inc. | Nuevos derivados de N-(4-(azetidina-1-carbonil)fenil)-(hetero-)arilsulfonamida como moduladores de piruvato quinasa M2 (PKM2) |
| JP6092118B2 (ja) | 2010-12-21 | 2017-03-08 | アジオス ファーマシューティカルズ， インコーポレイテッド | ニ環式ｐｋｍ２活性化剤 |
| TWI549947B (zh) | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| US9181231B2 (en) | 2011-05-03 | 2015-11-10 | Agios Pharmaceuticals, Inc | Pyruvate kinase activators for use for increasing lifetime of the red blood cells and treating anemia |
| WO2012151451A1 (en) | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc. | Pyruvate kinase activators for use in therapy |
| US9200001B2 (en) * | 2011-10-06 | 2015-12-01 | Merck Sharp & Dohme Corp. | Triazolyl PDE10 inhibitors |
| WO2014139144A1 (en) | 2013-03-15 | 2014-09-18 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| EP3285581B1 (en) | 2015-03-26 | 2021-08-11 | Merck Sharp & Dohme Corp. | Pyrazolyl pyrimidinone compounds as pde2 inhibitors |
| MA44392B1 (fr) | 2015-06-11 | 2023-10-31 | Agios Pharmaceuticals Inc | Procédés d'utilisation d'activateurs de la pyruvate kinase |
| PL3334431T3 (pl) | 2015-08-11 | 2020-03-31 | Novartis Ag | 5-bromo-2,6-di-(1H-pirazol-1-ilo)pirymidyno-4-amina do zastosowania w leczeniu nowotworu złośliwego |
| BR112021020906A2 (pt) * | 2019-04-18 | 2022-04-19 | Upl Ltd | Processo para a preparação de azoxistrobina e intermediários da mesma |
| JP2021187859A (ja) * | 2020-05-29 | 2021-12-13 | 大塚製薬株式会社 | 複素環化合物の医薬用途 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3040047A (en) * | 1960-04-04 | 1962-06-19 | Takeda Pharmaceutical | 2-(pyrazol-1-yl)-pyrimidine derivatives |
| US3647814A (en) * | 1969-07-03 | 1972-03-07 | Rohm & Haas | Method for preparing 4-substituted-1 2 4-triazoles |
| US3914223A (en) * | 1972-10-16 | 1975-10-21 | Rohm & Haas | 1,2,4,-4H-Triazole derivatives |
| JPS54115384A (en) * | 1978-02-28 | 1979-09-07 | Hokko Chem Ind Co Ltd | Ryrazolyl pyrimidine derivative, and agricultural and horticultural fungicides |
| US4725600A (en) * | 1984-07-13 | 1988-02-16 | Fujisawa Pharmaceutical Co., Ltd. | Pyrimidine compounds having activity as a cardiotonic anti-hypertensive cerebrovascular vasodilator and anti-platelet aggregation agent |
| JP2761673B2 (ja) * | 1990-12-14 | 1998-06-04 | 株式会社テイエルブイ | 熱応動式スチ―ムトラップ |
-
1986
- 1986-08-05 JP JP61184484A patent/JPS6339875A/ja active Granted
-
1987
- 1987-08-03 DE DE87306868T patent/DE3788385T2/de not_active Expired - Fee Related
- 1987-08-03 EP EP87306868A patent/EP0257850B1/en not_active Expired - Lifetime
- 1987-08-05 US US07/082,056 patent/US4849424A/en not_active Expired - Fee Related
- 1987-08-05 CA CA000543812A patent/CA1291757C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0257850A3 (en) | 1989-08-23 |
| JPS6339875A (ja) | 1988-02-20 |
| DE3788385T2 (de) | 1994-05-11 |
| EP0257850A2 (en) | 1988-03-02 |
| JPH0524917B2 (en, 2012) | 1993-04-09 |
| EP0257850B1 (en) | 1993-12-08 |
| DE3788385D1 (de) | 1994-01-20 |
| US4849424A (en) | 1989-07-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |