CA2406562C - Hiv replication inhibiting pyrimidines and triazines - Google Patents
Hiv replication inhibiting pyrimidines and triazines Download PDFInfo
- Publication number
- CA2406562C CA2406562C CA002406562A CA2406562A CA2406562C CA 2406562 C CA2406562 C CA 2406562C CA 002406562 A CA002406562 A CA 002406562A CA 2406562 A CA2406562 A CA 2406562A CA 2406562 C CA2406562 C CA 2406562C
- Authority
- CA
- Canada
- Prior art keywords
- 6alkyl
- formula
- compound
- amino
- cyano
- 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
- 230000010076 replication Effects 0.000 title abstract description 8
- 230000002401 inhibitory effect Effects 0.000 title description 10
- 150000003918 triazines Chemical class 0.000 title description 3
- 150000003230 pyrimidines Chemical class 0.000 title description 2
- 238000002360 preparation method Methods 0.000 claims abstract description 76
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 23
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
- 150000001412 amines Chemical group 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 16
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 260
- -1 cyano, aminocarbonyl Chemical group 0.000 claims description 157
- 239000000203 mixture Substances 0.000 claims description 90
- 239000002904 solvent Substances 0.000 claims description 83
- 125000005843 halogen group Chemical group 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 239000002585 base Substances 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 19
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 208000031886 HIV Infections Diseases 0.000 claims description 10
- 239000012298 atmosphere Substances 0.000 claims description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
- 230000000798 anti-retroviral effect Effects 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 6
- 208000037357 HIV infectious disease Diseases 0.000 claims description 6
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 6
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- WKKHLVSETHNCAY-UHFFFAOYSA-N 2-(4-cyanoanilino)-6-(2,4,6-trimethylanilino)pyrimidine-4-carboxamide Chemical compound CC1=CC(C)=CC(C)=C1NC1=CC(C(N)=O)=NC(NC=2C=CC(=CC=2)C#N)=N1 WKKHLVSETHNCAY-UHFFFAOYSA-N 0.000 claims description 2
- WMARVTJIFRNLQT-UHFFFAOYSA-N 5-bromo-2-(4-cyanoanilino)-6-(2,4,6-trimethylanilino)pyrimidine-4-carboxamide Chemical compound CC1=CC(C)=CC(C)=C1NC1=NC(NC=2C=CC(=CC=2)C#N)=NC(C(N)=O)=C1Br WMARVTJIFRNLQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 2
- ZBRAQRKOXKJAOV-UHFFFAOYSA-N 4-(4-cyanoanilino)-6-(2,4,6-trimethylanilino)-1,3,5-triazine-2-carboxamide Chemical compound CC1=CC(C)=CC(C)=C1NC1=NC(NC=2C=CC(=CC=2)C#N)=NC(C(N)=O)=N1 ZBRAQRKOXKJAOV-UHFFFAOYSA-N 0.000 claims 1
- 125000000815 N-oxide group Chemical group 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 29
- 239000003112 inhibitor Substances 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 6
- 235000013350 formula milk Nutrition 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 94
- 239000000543 intermediate Substances 0.000 description 92
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 77
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 60
- 239000007787 solid Substances 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- 229910001868 water Inorganic materials 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- 239000011541 reaction mixture Substances 0.000 description 37
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 35
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 28
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 27
- 150000003254 radicals Chemical class 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 229920000858 Cyclodextrin Polymers 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 229910052786 argon Inorganic materials 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 239000007832 Na2SO4 Substances 0.000 description 14
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 239000007962 solid dispersion Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 229920003169 water-soluble polymer Polymers 0.000 description 12
- 229940097362 cyclodextrins Drugs 0.000 description 11
- 229960004132 diethyl ether Drugs 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
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- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 8
- 125000006416 CBr Chemical group BrC* 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
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- 238000003756 stirring Methods 0.000 description 7
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 6
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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- 125000006239 protecting group Chemical group 0.000 description 5
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
- C07D251/50—Two nitrogen atoms with a halogen atom attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- AIDS & HIV (AREA)
- Communicable Diseases (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)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20247200P | 2000-05-08 | 2000-05-08 | |
| US60/202,472 | 2000-05-08 | ||
| PCT/EP2001/004991 WO2001085700A2 (en) | 2000-05-08 | 2001-05-03 | Hiv replication inhibiting pyrimidines and triazines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2406562A1 CA2406562A1 (en) | 2001-11-15 |
| CA2406562C true CA2406562C (en) | 2009-09-15 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA002406562A Expired - Lifetime CA2406562C (en) | 2000-05-08 | 2001-05-03 | Hiv replication inhibiting pyrimidines and triazines |
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| Country | Link |
|---|---|
| US (1) | US7276510B2 (enExample) |
| EP (1) | EP1282606B1 (enExample) |
| JP (1) | JP5230050B2 (enExample) |
| AR (1) | AR028423A1 (enExample) |
| AU (1) | AU783981C (enExample) |
| CA (1) | CA2406562C (enExample) |
| ES (1) | ES2542326T3 (enExample) |
| MY (1) | MY139506A (enExample) |
| PA (1) | PA8516401A1 (enExample) |
| WO (1) | WO2001085700A2 (enExample) |
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| WO2003011836A1 (en) * | 2001-08-01 | 2003-02-13 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| JO3429B1 (ar) | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | مشتقات برميدينات مثبطة فيروس الايدز |
| US8101629B2 (en) | 2001-08-13 | 2012-01-24 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
| US7638522B2 (en) | 2001-08-13 | 2009-12-29 | Janssen Pharmaceutica N.V. | Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile |
| US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-substituted pyrimidinyl derivatives and methods of use |
| US6939874B2 (en) | 2001-08-22 | 2005-09-06 | Amgen Inc. | Substituted pyrimidinyl derivatives and methods of use |
| DE60209381T2 (de) | 2001-10-26 | 2006-10-05 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | N-substituierte hydroxypyrimidinoncarboxamid-hemmer der hiv-integrase |
| ATE355064T1 (de) | 2001-10-26 | 2006-03-15 | Angeletti P Ist Richerche Bio | Dihydroxypyrimidin-carbonsäueramid-hemmer der hiv-integrase |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| AR039540A1 (es) * | 2002-05-13 | 2005-02-23 | Tibotec Pharm Ltd | Compuestos microbicidas con contenido de pirimidina o triazina |
| SE0201976D0 (sv) * | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| GB0215844D0 (en) | 2002-07-09 | 2002-08-14 | Novartis Ag | Organic compounds |
| DK1534286T3 (da) | 2002-07-29 | 2010-04-26 | Rigel Pharmaceuticals Inc | Fremgangsmåder til behandling eller forebyggelse af autoimmune sygdomme med 2,4-pyrimidindiamin-forbindelser |
| MY144894A (en) | 2002-08-09 | 2011-11-30 | Janssen Pharmaceutica Nv | Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2, 6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
| DE602004015254D1 (de) * | 2003-02-07 | 2008-09-04 | Janssen Pharmaceutica Nv | Hiv-inhibierende1,2,4-triazine |
| HRP20050688B1 (hr) | 2003-02-07 | 2017-03-24 | Janssen Pharmaceutica N.V. | Derivati pirimidina za sprječavanje hiv infekcije |
| CL2004000306A1 (es) | 2003-02-20 | 2005-04-08 | Tibotec Pharm Ltd | Compuestos derivados de pirimidina sustituidas con indano; proceso para su preparacion; composicion farmaceutica que lo comprende; combinacion farmaceutica; y su uso para el tratamiento o profilaxis de una enfermedad infecciosa. |
| EP1644338A1 (en) * | 2003-04-01 | 2006-04-12 | Aponetics AG | 2, 4, 6-trisubstituted pyrimidine derivatives useful for the treatment of neoplastic and autoimmune diseases |
| NZ545270A (en) | 2003-07-30 | 2010-04-30 | Rigel Pharmaceuticals Inc | 2,4-Pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases |
| BRPI0508854A (pt) * | 2004-03-17 | 2007-08-28 | Panacos Pharmaceuticals Inc | sais farmacêuticos de ácido-3-o-(3',3'-dimetilsuccinil) betulìnico |
| AU2005271161B2 (en) | 2004-08-10 | 2011-05-12 | Janssen Pharmaceutica N.V. | HIV inhibiting 1,2,4-triazin-6-one derivatives |
| RU2405778C2 (ru) * | 2004-09-30 | 2010-12-10 | Тиботек Фармасьютикалз Лтд. | 5-гетероциклилпиримидины, ингибирующие вич |
| BRPI0515935B8 (pt) | 2004-09-30 | 2021-05-25 | Janssen Sciences Ireland Uc | pirimidinas heterociclil- ou 5-carbo substituídas para inibição de hiv, e composição farmacêutica |
| AU2005288866B2 (en) * | 2004-09-30 | 2012-07-26 | Janssen Sciences Ireland Uc | HIV inhibiting 5-substituted pyrimidines |
| US8153640B2 (en) | 2004-10-29 | 2012-04-10 | Tibotec Pharmaceuticals Ltd. | HIV inhibiting bicyclic pyrimdine derivatives |
| ATE540035T1 (de) | 2004-11-24 | 2012-01-15 | Rigel Pharmaceuticals Inc | Spiro-2,4-pyrimidindiamin-verbindungen und ihre verwendungen |
| CN101068533B (zh) * | 2004-12-03 | 2011-04-27 | 默沙东公司 | 含有抗成核剂的药物组合物 |
| ES2337496T3 (es) | 2005-01-19 | 2010-04-26 | Rigel Pharmaceuticals, Inc. | Profarmacos de compuestos de 2,4-pirimidindiamina y sus usos. |
| JP2008535923A (ja) * | 2005-04-12 | 2008-09-04 | パナコス ファーマシューティカルズ インコーポレーティッド | ３−ｏ−（３’，３’−ジメチルスクシニル）ベツリン酸ジ−ｎ−メチル−ｄ−グルカミンの多形 |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| US7491732B2 (en) | 2005-06-08 | 2009-02-17 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
| SI2004641T1 (sl) * | 2006-03-30 | 2011-02-28 | Tibotec Pharm Ltd | HIV inhibirajoči 5-(hidroksimetilen in aminometilen) substituirani pirimidini |
| RU2480464C2 (ru) | 2006-03-30 | 2013-04-27 | Тиботек Фармасьютикалз Лтд. | 5-амидо-замещенные пиримидины, ингибирующие вич |
| EA019966B1 (ru) | 2006-12-08 | 2014-07-30 | АйАрЭм ЭлЭлСи | Соединения и композиции в качестве ингибиторов протеинкиназы |
| US8318736B2 (en) | 2006-12-29 | 2012-11-27 | Janssen R&D Ireland | HIV inhibiting 5,6-substituted pyrimidines |
| KR20090094073A (ko) * | 2006-12-29 | 2009-09-03 | 티보텍 파마슈티칼즈 리미티드 | Ｈｉｖ를 억제하는 6-치환된 피리미딘 |
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| ES2645689T5 (en) | 2008-05-21 | 2025-06-24 | Takeda Pharmaceuticals Co | Phosphorous derivatives as kinase inhibitors |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| WO2011017079A1 (en) | 2009-07-27 | 2011-02-10 | Teva Pharmaceutical Industries Ltd. | Process for the preparation and purification of etravirine and intermediates thereof |
| GR1007010B (el) | 2009-10-08 | 2010-10-07 | Χημικα Και Βιοφαρμακευτικα Εργαστηρια Πατρων Αε (Cbl-Patras), | Ινσουλινοειδη πεπτιδια |
| PT2576541T (pt) | 2010-06-04 | 2016-07-08 | Hoffmann La Roche | Derivados de aminopirimidina como moduladores de lrrk2 |
| SG189043A1 (en) | 2010-11-10 | 2013-05-31 | Hoffmann La Roche | Pyrazole aminopyrimidine derivatives as lrrk2 modulators |
| KR101884010B1 (ko) | 2011-05-04 | 2018-07-31 | 어리어드 파마슈티칼스, 인코포레이티드 | Egfr-유도된 암의 세포 증식을 억제하는 화합물 |
| CN102260215A (zh) * | 2011-05-13 | 2011-11-30 | 复旦大学 | 一种二芳基嘧啶类衍生物及其制备方法和用途 |
| WO2013047411A1 (ja) * | 2011-09-29 | 2013-04-04 | 富士フイルム株式会社 | 新規なトリアジン誘導体、紫外線吸収剤 |
| US20130123498A1 (en) | 2011-10-19 | 2013-05-16 | Maja Sepelj MAJER | Process for the preparation of etravirine and intermediates in the synthesis thereof |
| GB201119358D0 (en) | 2011-11-10 | 2011-12-21 | Lewi Paulus J | Disubstituted triazine dimers for treatment and/or prevention of infectious diseases |
| CN104066431B (zh) | 2011-11-23 | 2017-03-08 | 波托拉医药品公司 | 吡嗪激酶抑制剂 |
| GB201204756D0 (en) | 2012-03-19 | 2012-05-02 | Lewi Paulus J | Triazines with suitable spacers for treatment and/or prevention of HIV infections |
| JP6469567B2 (ja) | 2012-05-05 | 2019-02-13 | アリアド・ファーマシューティカルズ・インコーポレイテッド | Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物 |
| WO2014072419A1 (en) | 2012-11-08 | 2014-05-15 | Universiteit Antwerpen | Novel anti-hiv compounds |
| US9145387B2 (en) | 2013-02-08 | 2015-09-29 | Celgene Avilomics Research, Inc. | ERK inhibitors and uses thereof |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN111620830A (zh) * | 2014-03-14 | 2020-09-04 | 北卡罗来纳大学教堂山分校 | 用于抑制雄性生育力的小分子 |
| TW201613892A (en) | 2014-08-13 | 2016-04-16 | Celgene Avilomics Res Inc | Forms and compositions of an ERK inhibitor |
| SG11202112171XA (en) | 2019-05-10 | 2021-12-30 | Deciphera Pharmaceuticals Llc | Heteroarylaminopyrimidine amide autophagy inhibitors and methods of use thereof |
| CN118930524A (zh) | 2019-05-10 | 2024-11-12 | 德西费拉制药有限责任公司 | 苯基氨基嘧啶酰胺自噬抑制剂及其使用方法 |
| AU2020297422B2 (en) | 2019-06-17 | 2024-03-21 | Deciphera Pharmaceuticals, Llc | Aminopyrimidine amide autophagy inhibitors and methods of use thereof |
| EP4335847A1 (en) * | 2021-05-07 | 2024-03-13 | Voronoi Inc. | Heteroaryl derivative, method for preparing same, and pharmaceutical composition comprising same as active ingredient |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US2433439A (en) * | 1947-12-30 | Pyrimidine compounds | ||
| GB854011A (en) * | 1958-09-10 | 1960-11-16 | Ici Ltd | New pyrimidines |
| NL129020C (enExample) * | 1964-12-15 | |||
| US3459731A (en) | 1966-12-16 | 1969-08-05 | Corn Products Co | Cyclodextrin polyethers and their production |
| US4659363A (en) * | 1983-07-25 | 1987-04-21 | Ciba-Geigy Corporation | N-(2-nitrophenyl)-2-aminopyrimidine derivatives, the preparation and use thereof |
| JPH0784445B2 (ja) * | 1986-12-03 | 1995-09-13 | クミアイ化学工業株式会社 | ピリミジン誘導体および農園芸用殺菌剤 |
| GB9012592D0 (en) * | 1990-06-06 | 1990-07-25 | Smithkline Beecham Intercredit | Compounds |
| GB9016800D0 (en) * | 1990-07-31 | 1990-09-12 | Shell Int Research | Tetrahydropyrimidine derivatives |
| US5516775A (en) | 1992-08-31 | 1996-05-14 | Ciba-Geigy Corporation | Further use of pyrimidine derivatives |
| RU2153494C2 (ru) | 1993-10-12 | 2000-07-27 | Дзе Дюпон Мерк Фармасьютикал Компани | 1-n-алкил-n-арилпиримидинамины, способ лечения заболеваний, фармацевтическая композиция |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| WO1997018839A1 (en) | 1995-11-23 | 1997-05-29 | Janssen Pharmaceutica N.V. | Solid mixtures of cyclodextrins prepared via melt-extrusion |
| CN1163401A (zh) | 1996-02-13 | 1997-10-29 | 李占元 | 全自动血球计数仪试剂及配制方法 |
| NO311614B1 (no) | 1996-10-01 | 2001-12-17 | Janssen Pharmaceutica Nv | Substituerte diamino-1,3,5-triazinderivater |
| GB9705361D0 (en) * | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| ES2308821T3 (es) * | 1997-12-15 | 2008-12-01 | Astellas Pharma Inc. | Nuevos derivados de pirimidin-5-carboxamida. |
| CN1297447A (zh) * | 1998-02-17 | 2001-05-30 | 图拉列克股份有限公司 | 抗病毒嘧啶衍生物 |
| EP0945443B9 (en) * | 1998-03-27 | 2003-08-13 | Janssen Pharmaceutica N.V. | HIV inhibiting pyrimidine derivatives |
| EP0945447A1 (en) | 1998-03-27 | 1999-09-29 | Janssen Pharmaceutica N.V. | Trisubstituted 1,3,5-triazine derivatives for treatment of HIV infections |
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| OA11674A (en) | 1998-11-10 | 2005-01-12 | Janssen Pharmaceutica Nv | HIV Replication inhibiting pyrimidines. |
| GB9828511D0 (en) * | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
-
2001
- 2001-05-03 AU AU56333/01A patent/AU783981C/en not_active Expired
- 2001-05-03 US US10/275,931 patent/US7276510B2/en not_active Expired - Lifetime
- 2001-05-03 CA CA002406562A patent/CA2406562C/en not_active Expired - Lifetime
- 2001-05-03 WO PCT/EP2001/004991 patent/WO2001085700A2/en not_active Ceased
- 2001-05-03 EP EP01929616.9A patent/EP1282606B1/en not_active Expired - Lifetime
- 2001-05-03 JP JP2001582301A patent/JP5230050B2/ja not_active Expired - Lifetime
- 2001-05-03 ES ES01929616.9T patent/ES2542326T3/es not_active Expired - Lifetime
- 2001-05-04 MY MYPI20012096A patent/MY139506A/en unknown
- 2001-05-07 AR ARP010102147A patent/AR028423A1/es not_active Application Discontinuation
- 2001-05-08 PA PA20018516401A patent/PA8516401A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1282606A2 (en) | 2003-02-12 |
| CA2406562A1 (en) | 2001-11-15 |
| ES2542326T3 (es) | 2015-08-04 |
| US20030171374A1 (en) | 2003-09-11 |
| JP2003535828A (ja) | 2003-12-02 |
| WO2001085700A3 (en) | 2002-02-07 |
| WO2001085700A2 (en) | 2001-11-15 |
| AU783981C (en) | 2007-05-03 |
| US7276510B2 (en) | 2007-10-02 |
| AU783981B2 (en) | 2006-01-12 |
| AU5633301A (en) | 2001-11-20 |
| MY139506A (en) | 2009-10-30 |
| JP5230050B2 (ja) | 2013-07-10 |
| PA8516401A1 (es) | 2002-02-21 |
| AR028423A1 (es) | 2003-05-07 |
| EP1282606B1 (en) | 2015-04-22 |
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