CA1254563A - Imidazo ¬5,1-d| tetrazin-1,2,3,5 one-derivatives and related products, processes for their preparation and composition containing said derivatives - Google Patents
Imidazo ¬5,1-d| tetrazin-1,2,3,5 one-derivatives and related products, processes for their preparation and composition containing said derivativesInfo
- Publication number
- CA1254563A CA1254563A CA000434582A CA434582A CA1254563A CA 1254563 A CA1254563 A CA 1254563A CA 000434582 A CA000434582 A CA 000434582A CA 434582 A CA434582 A CA 434582A CA 1254563 A CA1254563 A CA 1254563A
- Authority
- CA
- Canada
- Prior art keywords
- group
- carbon atoms
- group containing
- substituted
- substituents selected
- 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
- 238000000034 method Methods 0.000 title claims abstract description 76
- 238000002360 preparation method Methods 0.000 title claims abstract description 57
- 239000000203 mixture Substances 0.000 title claims description 106
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 183
- 125000001424 substituent group Chemical group 0.000 claims abstract description 155
- 125000005843 halogen group Chemical group 0.000 claims abstract description 137
- 150000001875 compounds Chemical class 0.000 claims abstract description 127
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 126
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 118
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 114
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 72
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 58
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 54
- 150000004905 tetrazines Chemical class 0.000 claims abstract description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 32
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 28
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- 239000001301 oxygen Substances 0.000 claims abstract description 24
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 12
- 239000005864 Sulphur Chemical group 0.000 claims abstract description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 332
- 125000003545 alkoxy group Chemical group 0.000 claims description 134
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 70
- BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 claims description 49
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 25
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 22
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 17
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 11
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 11
- 230000006978 adaptation Effects 0.000 claims description 10
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 8
- 229940124530 sulfonamide Drugs 0.000 claims description 8
- 229910052717 sulfur Chemical group 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 7
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 claims description 6
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 5
- 238000006396 nitration reaction Methods 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- HQQOOAOVOVCGGM-UHFFFAOYSA-N 4-diazo-2-methyl-5-methylsulfonylimidazole Chemical compound CC1=NC(=[N+]=[N-])C(S(C)(=O)=O)=N1 HQQOOAOVOVCGGM-UHFFFAOYSA-N 0.000 claims description 4
- WZNLIHBAMSARDC-UHFFFAOYSA-N 4-diazo-5-methylsulfonylimidazole Chemical compound CS(=O)(=O)C1=NC=NC1=[N+]=[N-] WZNLIHBAMSARDC-UHFFFAOYSA-N 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 claims description 4
- AOXBCWSUKKUDEW-UHFFFAOYSA-N [N+](=[N-])=C1C(=NC(=N1)CCC)C(=O)N Chemical compound [N+](=[N-])=C1C(=NC(=N1)CCC)C(=O)N AOXBCWSUKKUDEW-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 238000006264 debenzylation reaction Methods 0.000 claims description 4
- 229910017604 nitric acid Inorganic materials 0.000 claims description 4
- 239000001117 sulphuric acid Substances 0.000 claims description 4
- 235000011149 sulphuric acid Nutrition 0.000 claims description 4
- FPJOCIZOSGXPGL-UHFFFAOYSA-N 2-butyl-5-diazoimidazole-4-carboxamide Chemical compound C(CCC)C1=NC(C(=N1)C(=O)N)=[N+]=[N-] FPJOCIZOSGXPGL-UHFFFAOYSA-N 0.000 claims description 3
- ZNSWWWOHNIHHPP-UHFFFAOYSA-N 3-(2-chloroethyl)-8-methylsulfonylimidazo[5,1-d][1,2,3,5]tetrazin-4-one Chemical compound N1=NN(CCCl)C(=O)N2C1=C(S(=O)(=O)C)N=C2 ZNSWWWOHNIHHPP-UHFFFAOYSA-N 0.000 claims description 3
- BQSJKVZIMIYYKM-UHFFFAOYSA-N 3-diazopyrazole-4-carboxamide Chemical compound NC(=O)C1=CN=NC1=[N+]=[N-] BQSJKVZIMIYYKM-UHFFFAOYSA-N 0.000 claims description 3
- XRKHMOZFJQLSJR-UHFFFAOYSA-N 3-methyl-8-methylsulfonylimidazo[5,1-d][1,2,3,5]tetrazin-4-one Chemical compound CN1N=NC=2N(C1=O)C=NC2S(=O)(=O)C XRKHMOZFJQLSJR-UHFFFAOYSA-N 0.000 claims description 3
- RREVXGBSLCCEKT-UHFFFAOYSA-N 5-diazo-N,N,2-trimethylimidazole-4-sulfonamide Chemical compound [N+](=[N-])=C1C(=NC(=N1)C)S(N(C)C)(=O)=O RREVXGBSLCCEKT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- MTTANBKQUNTRGF-UHFFFAOYSA-N 3-(2-chloroethyl)-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-sulfonamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(S(=O)(=O)N)N=C2 MTTANBKQUNTRGF-UHFFFAOYSA-N 0.000 claims description 2
- DYFOLIVSADVMQX-UHFFFAOYSA-N 3-(2-chloroethyl)-8-methylsulfonylpyrazolo[5,1-d][1,2,3,5]tetrazin-4-one Chemical compound N1=NN(CCCl)C(=O)N2C1=C(S(=O)(=O)C)C=N2 DYFOLIVSADVMQX-UHFFFAOYSA-N 0.000 claims description 2
- LXKYNXDRSSBLME-UHFFFAOYSA-N 5-diazo-2-methylimidazole-4-carboxamide Chemical compound [N+](=[N-])=C1C(=NC(=N1)C)C(=O)N LXKYNXDRSSBLME-UHFFFAOYSA-N 0.000 claims description 2
- CGUOOAJNXYGEFB-UHFFFAOYSA-N 3-(2-chloroethyl)-8-(piperidine-1-carbonyl)imidazo[5,1-d][1,2,3,5]tetrazin-4-one Chemical compound N1=CN2C(=O)N(CCCl)N=NC2=C1C(=O)N1CCCCC1 CGUOOAJNXYGEFB-UHFFFAOYSA-N 0.000 claims 2
- BCSDQRFQGUJUKI-UHFFFAOYSA-N 3-(2-chloroethyl)-N-[(4-methoxyphenyl)methyl]-6-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-sulfonamide Chemical compound ClCCN1N=NC=2N(C1=O)C(=NC2S(NCC2=CC=C(C=C2)OC)(=O)=O)C BCSDQRFQGUJUKI-UHFFFAOYSA-N 0.000 claims 2
- TVYRKSKMTZTXSN-UHFFFAOYSA-N 3-(2-chloroethyl)-n,n-dimethyl-4-oxopyrazolo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(C(=O)N(C)C)C=N2 TVYRKSKMTZTXSN-UHFFFAOYSA-N 0.000 claims 2
- CUNKBKXWDQMEOE-UHFFFAOYSA-N 3-(2-chloroethyl)-n-nitro-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(C(=O)N[N+](=O)[O-])N=C2 CUNKBKXWDQMEOE-UHFFFAOYSA-N 0.000 claims 2
- QRKTVLUUPAGXLL-UHFFFAOYSA-N 6-butyl-3-(2-chloroethyl)-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C(CCCC)=NC(C(N)=O)=C21 QRKTVLUUPAGXLL-UHFFFAOYSA-N 0.000 claims 2
- PDGHAGNLCZOMJA-UHFFFAOYSA-N n-benzyl-3-(2-chloroethyl)-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=CN2C(=O)N(CCCl)N=NC2=C1C(=O)NCC1=CC=CC=C1 PDGHAGNLCZOMJA-UHFFFAOYSA-N 0.000 claims 2
- OXLCXBVBLSAUJO-UHFFFAOYSA-N 3-(2-chloroethyl)-4-oxo-6-propan-2-ylimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C(C(C)C)=NC(C(N)=O)=C21 OXLCXBVBLSAUJO-UHFFFAOYSA-N 0.000 claims 1
- GCOAJPQTYKOBSK-UHFFFAOYSA-N 3-(2-chloroethyl)-4-oxopyrazolo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(C(=O)N)C=N2 GCOAJPQTYKOBSK-UHFFFAOYSA-N 0.000 claims 1
- DIBUJGHFHUZTOU-UHFFFAOYSA-N 3-(2-chloroethyl)-6-cyclohexyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(C(=O)N)N=C2C1CCCCC1 DIBUJGHFHUZTOU-UHFFFAOYSA-N 0.000 claims 1
- MMSMNBAMEBSIKH-UHFFFAOYSA-N 3-(2-chloroethyl)-6-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C(C)=NC(C(N)=O)=C21 MMSMNBAMEBSIKH-UHFFFAOYSA-N 0.000 claims 1
- YKHGJGVERXYXBH-UHFFFAOYSA-N 3-(2-chloroethyl)-6-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-sulfonamide Chemical compound ClCCN1N=NC=2N(C1=O)C(=NC2S(N)(=O)=O)C YKHGJGVERXYXBH-UHFFFAOYSA-N 0.000 claims 1
- ZADSVILBOFLJFF-UHFFFAOYSA-N 3-(2-chloroethyl)-6-methyl-8-methylsulfinylimidazo[5,1-d][1,2,3,5]tetrazin-4-one Chemical compound ClCCN1N=NC=2N(C1=O)C(=NC2S(=O)C)C ZADSVILBOFLJFF-UHFFFAOYSA-N 0.000 claims 1
- CAHWKRMIWNDLCP-UHFFFAOYSA-N 3-(2-chloroethyl)-8-ethylsulfonyl-6-methylimidazo[5,1-d][1,2,3,5]tetrazin-4-one Chemical compound ClCCN1N=NC=2N(C1=O)C(=NC2S(=O)(=O)CC)C CAHWKRMIWNDLCP-UHFFFAOYSA-N 0.000 claims 1
- VWWNGDYKIZWUHM-UHFFFAOYSA-N 3-(2-chloroethyl)-N-[(4-methoxyphenyl)methyl]-4-oxo-N-phenylimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound ClCCN1N=NC=2N(C1=O)C=NC2C(N(C2=CC=CC=C2)CC2=CC=C(C=C2)OC)=O VWWNGDYKIZWUHM-UHFFFAOYSA-N 0.000 claims 1
- YJQJSSZIAYYUEO-UHFFFAOYSA-N 3-(2-chloroethyl)-n,n-dimethyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-sulfonamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(S(=O)(=O)N(C)C)N=C2 YJQJSSZIAYYUEO-UHFFFAOYSA-N 0.000 claims 1
- JBUYYXUMLKLCKB-UHFFFAOYSA-N 3-(2-chloroethyl)-n-[(4-methoxyphenyl)methyl]-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-sulfonamide Chemical compound C1=CC(OC)=CC=C1CNS(=O)(=O)C1=C(N=NN(CCCl)C2=O)N2C=N1 JBUYYXUMLKLCKB-UHFFFAOYSA-N 0.000 claims 1
- QRSVUTWZXVDUEA-UHFFFAOYSA-N 3-(2-chloroethyl)-n-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-sulfonamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(S(=O)(=O)NC)N=C2 QRSVUTWZXVDUEA-UHFFFAOYSA-N 0.000 claims 1
- NHXAXFAKTMZCOV-UHFFFAOYSA-N 3-methyl-4-oxopyrazolo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)C=NN21 NHXAXFAKTMZCOV-UHFFFAOYSA-N 0.000 claims 1
- SBKFUIRJCGCFNK-UHFFFAOYSA-N 6-benzyl-3-(2-chloroethyl)-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(C(=O)N)N=C2CC1=CC=CC=C1 SBKFUIRJCGCFNK-UHFFFAOYSA-N 0.000 claims 1
- VFZNLFWMVBFQMV-UHFFFAOYSA-N N-benzyl-3-(2-chloroethyl)-N-[(4-methoxyphenyl)methyl]-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide Chemical compound C(C1=CC=CC=C1)N(C(=O)C=1N=CN2C1N=NN(C2=O)CCCl)CC2=CC=C(C=C2)OC VFZNLFWMVBFQMV-UHFFFAOYSA-N 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 6
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 4
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 abstract 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 abstract 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 1
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 abstract 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical class CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 228
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 146
- 239000000243 solution Substances 0.000 description 127
- 239000007787 solid Substances 0.000 description 91
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- 238000000354 decomposition reaction Methods 0.000 description 40
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- 239000000460 chlorine Substances 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000000921 elemental analysis Methods 0.000 description 20
- 239000003208 petroleum Substances 0.000 description 19
- 235000010288 sodium nitrite Nutrition 0.000 description 19
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical class CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 11
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 11
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- 229910000564 Raney nickel Inorganic materials 0.000 description 10
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
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- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
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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
- C07D231/14—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- 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
- C07D231/14—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
-
- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
-
- 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
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8223583 | 1982-08-17 | ||
| GB8223580 | 1982-08-17 | ||
| GB8223580 | 1982-08-17 | ||
| GB8223583 | 1982-08-17 | ||
| GB8226169 | 1982-09-14 | ||
| GB8226169 | 1982-09-14 | ||
| GB838306904A GB8306904D0 (en) | 1983-03-14 | 1983-03-14 | Compositions of matter |
| GB8306904 | 1983-03-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1254563A true CA1254563A (en) | 1989-05-23 |
Family
ID=27449377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000434582A Expired CA1254563A (en) | 1982-08-17 | 1983-08-15 | Imidazo ¬5,1-d| tetrazin-1,2,3,5 one-derivatives and related products, processes for their preparation and composition containing said derivatives |
Country Status (18)
| Country | Link |
|---|---|
| AU (1) | AU575782B2 (de) |
| BE (1) | BE897548A (de) |
| CA (1) | CA1254563A (de) |
| CH (1) | CH657855A5 (de) |
| DE (1) | DE3329505A1 (de) |
| DK (1) | DK374983A (de) |
| ES (1) | ES524995A0 (de) |
| FI (1) | FI80273C (de) |
| FR (1) | FR2531958B1 (de) |
| GR (1) | GR78688B (de) |
| HU (1) | HU189321B (de) |
| IE (1) | IE55849B1 (de) |
| IL (1) | IL69500A (de) |
| IT (1) | IT1194375B (de) |
| LU (1) | LU84969A1 (de) |
| NL (1) | NL8302863A (de) |
| NZ (1) | NZ205272A (de) |
| SE (1) | SE455198B (de) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2932305A1 (de) * | 1979-08-09 | 1981-02-26 | Basf Ag | Azolo- eckige klammer auf 5,1-d eckige klammer zu - eckige klammer auf 1,2,3,5 eckige klammer zu -tetrazin-4-one und verfahren zur herstellung dieser verbindungen |
| OA07174A (fr) * | 1981-08-24 | 1984-04-30 | May & Baker Ltd | Nouvelles imidazotétrazionones, leur préparation et les médicaments qui les contiennent. |
-
1983
- 1983-08-12 FR FR8313246A patent/FR2531958B1/fr not_active Expired
- 1983-08-12 GR GR72210A patent/GR78688B/el unknown
- 1983-08-15 CA CA000434582A patent/CA1254563A/en not_active Expired
- 1983-08-15 HU HU832860A patent/HU189321B/hu unknown
- 1983-08-15 SE SE8304415A patent/SE455198B/sv not_active IP Right Cessation
- 1983-08-15 IE IE1913/83A patent/IE55849B1/xx unknown
- 1983-08-15 AU AU17968/83A patent/AU575782B2/en not_active Ceased
- 1983-08-15 IL IL69500A patent/IL69500A/xx unknown
- 1983-08-15 FI FI832927A patent/FI80273C/fi not_active IP Right Cessation
- 1983-08-15 NZ NZ205272A patent/NZ205272A/en unknown
- 1983-08-15 NL NL8302863A patent/NL8302863A/nl not_active Application Discontinuation
- 1983-08-16 DK DK374983A patent/DK374983A/da not_active Application Discontinuation
- 1983-08-16 LU LU84969A patent/LU84969A1/fr unknown
- 1983-08-16 IT IT22566/83A patent/IT1194375B/it active
- 1983-08-16 DE DE3329505A patent/DE3329505A1/de not_active Withdrawn
- 1983-08-17 BE BE0/211366A patent/BE897548A/fr not_active IP Right Cessation
- 1983-08-17 CH CH4490/83A patent/CH657855A5/fr not_active IP Right Cessation
- 1983-08-17 ES ES83524995A patent/ES524995A0/es active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| IE831913L (en) | 1984-02-17 |
| IL69500A (en) | 1989-01-31 |
| SE8304415D0 (sv) | 1983-08-15 |
| FR2531958B1 (fr) | 1986-10-31 |
| FI832927A (fi) | 1984-02-18 |
| IT8322566A0 (it) | 1983-08-16 |
| AU575782B2 (en) | 1988-08-11 |
| ES8502441A1 (es) | 1985-01-01 |
| GR78688B (de) | 1984-09-27 |
| FI80273B (fi) | 1990-01-31 |
| CH657855A5 (fr) | 1986-09-30 |
| NL8302863A (nl) | 1984-03-16 |
| HU189321B (en) | 1986-06-30 |
| FI832927A0 (fi) | 1983-08-15 |
| FI80273C (fi) | 1990-05-10 |
| BE897548A (fr) | 1984-02-17 |
| SE455198B (sv) | 1988-06-27 |
| DE3329505A1 (de) | 1984-02-23 |
| NZ205272A (en) | 1986-12-05 |
| IT1194375B (it) | 1988-09-22 |
| DK374983A (da) | 1984-02-18 |
| ES524995A0 (es) | 1985-01-01 |
| IE55849B1 (en) | 1991-01-30 |
| DK374983D0 (da) | 1983-08-16 |
| SE8304415L (sv) | 1984-02-18 |
| LU84969A1 (fr) | 1984-03-23 |
| AU1796883A (en) | 1984-02-23 |
| FR2531958A1 (fr) | 1984-02-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |