ES2589283T3 - Agentes anti-malaria - Google Patents
Agentes anti-malaria Download PDFInfo
- Publication number
- ES2589283T3 ES2589283T3 ES13712926.8T ES13712926T ES2589283T3 ES 2589283 T3 ES2589283 T3 ES 2589283T3 ES 13712926 T ES13712926 T ES 13712926T ES 2589283 T3 ES2589283 T3 ES 2589283T3
- Authority
- ES
- Spain
- Prior art keywords
- optionally substituted
- formula
- phenyl
- mmol
- trifluoromethyl
- 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.)
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- 239000003430 antimalarial agent Substances 0.000 title description 2
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 abstract description 35
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 21
- -1 complexes Chemical class 0.000 abstract description 17
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract description 7
- 150000003839 salts Chemical class 0.000 abstract description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
- 125000001424 substituent group Chemical group 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract 2
- 150000002367 halogens Chemical class 0.000 abstract 2
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 50
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 239000011541 reaction mixture Substances 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 34
- 239000007787 solid Substances 0.000 description 31
- 239000000543 intermediate Substances 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 239000000203 mixture Substances 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 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 239000007832 Na2SO4 Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- BNTIPMNMTIAWIW-UHFFFAOYSA-N [6-(trifluoromethyl)pyridin-3-yl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)N=C1 BNTIPMNMTIAWIW-UHFFFAOYSA-N 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- KRRTXVSBTPCDOS-UHFFFAOYSA-N 5-bromopyrazin-2-amine Chemical compound NC1=CN=C(Br)C=N1 KRRTXVSBTPCDOS-UHFFFAOYSA-N 0.000 description 5
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 201000004792 malaria Diseases 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 4
- 244000045947 parasite Species 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000223960 Plasmodium falciparum Species 0.000 description 3
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- GNRHNKBJNUVWFZ-UHFFFAOYSA-N (4-carbamoylphenyl)boronic acid Chemical compound NC(=O)C1=CC=C(B(O)O)C=C1 GNRHNKBJNUVWFZ-UHFFFAOYSA-N 0.000 description 2
- VDUKDQTYMWUSAC-UHFFFAOYSA-N (4-methylsulfonylphenyl)boronic acid Chemical compound CS(=O)(=O)C1=CC=C(B(O)O)C=C1 VDUKDQTYMWUSAC-UHFFFAOYSA-N 0.000 description 2
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 2
- TVMWNJXWFMZIPH-UHFFFAOYSA-N 3-bromo-5-(4-methylsulfonylphenyl)pyrazin-2-amine Chemical group C1=CC(S(=O)(=O)C)=CC=C1C1=CN=C(N)C(Br)=N1 TVMWNJXWFMZIPH-UHFFFAOYSA-N 0.000 description 2
- BFEUGUAUYFATRV-UHFFFAOYSA-N 3-bromopyrazin-2-amine Chemical class NC1=NC=CN=C1Br BFEUGUAUYFATRV-UHFFFAOYSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- XDETXTPYFPJKPS-UHFFFAOYSA-N 5-bromo-3-(6-methoxypyridin-3-yl)pyrazin-2-amine Chemical group C1=NC(OC)=CC=C1C1=NC(Br)=CN=C1N XDETXTPYFPJKPS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- KMNLIQJXZPBCDU-UHFFFAOYSA-N [4-(morpholine-4-carbonyl)phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C(=O)N1CCOCC1 KMNLIQJXZPBCDU-UHFFFAOYSA-N 0.000 description 2
- 229960004191 artemisinin Drugs 0.000 description 2
- 229930101531 artemisinin Natural products 0.000 description 2
- 229960003159 atovaquone Drugs 0.000 description 2
- KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical class N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 229960003722 doxycycline Drugs 0.000 description 2
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 2
- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 150000003235 pyrrolidines Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229940086542 triethylamine Drugs 0.000 description 2
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 description 1
- IFSRLALWNRZNIR-UHFFFAOYSA-N (3-aminopyrrolidin-1-yl)-[4-[5-amino-6-[4-(trifluoromethyl)phenyl]pyrazin-2-yl]phenyl]methanone Chemical compound C1C(N)CCN1C(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2C=CC(=CC=2)C(F)(F)F)C=C1 IFSRLALWNRZNIR-UHFFFAOYSA-N 0.000 description 1
- ATFCGTCYACZEPJ-UHFFFAOYSA-N (3-aminopyrrolidin-1-yl)-[4-[5-amino-6-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-yl]phenyl]methanone Chemical compound C1C(N)CCN1C(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2C=NC(=CC=2)C(F)(F)F)C=C1 ATFCGTCYACZEPJ-UHFFFAOYSA-N 0.000 description 1
- FGEWQKLJXCFIGT-UHFFFAOYSA-N (4-aminopiperidin-1-yl)-[4-[5-amino-6-[4-(trifluoromethyl)phenyl]pyrazin-2-yl]phenyl]methanone Chemical compound C1CC(N)CCN1C(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2C=CC(=CC=2)C(F)(F)F)C=C1 FGEWQKLJXCFIGT-UHFFFAOYSA-N 0.000 description 1
- QZNPPKWFTCQHST-UHFFFAOYSA-N (4-aminopiperidin-1-yl)-[4-[5-amino-6-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-yl]phenyl]methanone Chemical compound C1CC(N)CCN1C(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2C=NC(=CC=2)C(F)(F)F)C=C1 QZNPPKWFTCQHST-UHFFFAOYSA-N 0.000 description 1
- DHADXDMPEUWEAS-UHFFFAOYSA-N (6-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=N1 DHADXDMPEUWEAS-UHFFFAOYSA-N 0.000 description 1
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- MSGBHWXJZXCMDF-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-5-(4-methylsulfonylphenyl)pyrazin-2-amine Chemical compound C1=NC(OC)=CC=C1C1=NC(C=2C=CC(=CC=2)S(C)(=O)=O)=CN=C1N MSGBHWXJZXCMDF-UHFFFAOYSA-N 0.000 description 1
- WUKANDNCRFGEHC-UHFFFAOYSA-N 3-(dimethylamino)propyl-(ethyliminomethylidene)azanium;chloride;hydrochloride Chemical compound Cl.Cl.CCN=C=NCCCN(C)C WUKANDNCRFGEHC-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- HDACDDSPBQTVCH-UHFFFAOYSA-N 3-hydroxypyrrolidine-1-carbaldehyde Chemical compound OC1CCN(C=O)C1 HDACDDSPBQTVCH-UHFFFAOYSA-N 0.000 description 1
- NPGXJTVGTZFRFV-UHFFFAOYSA-N 4-(5-aminopyrazin-2-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CN=C(N)C=N1 NPGXJTVGTZFRFV-UHFFFAOYSA-N 0.000 description 1
- XNPURVXRWUXOPE-UHFFFAOYSA-N 4-[5-amino-6-[3-fluoro-4-(trifluoromethyl)phenyl]pyrazin-2-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CN=C(N)C(C=2C=C(F)C(=CC=2)C(F)(F)F)=N1 XNPURVXRWUXOPE-UHFFFAOYSA-N 0.000 description 1
- UBIZVPPIFUXEEB-UHFFFAOYSA-N 4-[5-amino-6-[4-(trifluoromethyl)phenyl]pyrazin-2-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CN=C(N)C(C=2C=CC(=CC=2)C(F)(F)F)=N1 UBIZVPPIFUXEEB-UHFFFAOYSA-N 0.000 description 1
- FRVNCQOSGYBWDN-UHFFFAOYSA-N 4-[5-amino-6-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CN=C(N)C(C=2C=NC(=CC=2)C(F)(F)F)=N1 FRVNCQOSGYBWDN-UHFFFAOYSA-N 0.000 description 1
- LUBUTTBEBGYNJN-UHFFFAOYSA-N 4-amino-n-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide;5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1.COC1=NC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1OC LUBUTTBEBGYNJN-UHFFFAOYSA-N 0.000 description 1
- SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- WNLGPWQMIXOKQG-UHFFFAOYSA-N 5-(4-cyclopropylsulfonylphenyl)-3-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-amine Chemical compound NC1=NC=C(C=2C=CC(=CC=2)S(=O)(=O)C2CC2)N=C1C1=CC=C(C(F)(F)F)N=C1 WNLGPWQMIXOKQG-UHFFFAOYSA-N 0.000 description 1
- MOVWXDGLBZSEPD-UHFFFAOYSA-N 5-(4-ethylsulfonylphenyl)-3-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-amine Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C1=CN=C(N)C(C=2C=NC(=CC=2)C(F)(F)F)=N1 MOVWXDGLBZSEPD-UHFFFAOYSA-N 0.000 description 1
- FRRKZFCMZMHXEM-UHFFFAOYSA-N 5-(4-methylsulfonylphenyl)-3-[4-(trifluoromethyl)phenyl]pyrazin-2-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CN=C(N)C(C=2C=CC(=CC=2)C(F)(F)F)=N1 FRRKZFCMZMHXEM-UHFFFAOYSA-N 0.000 description 1
- PXDXGCHQPAYYEN-UHFFFAOYSA-N 5-(4-methylsulfonylphenyl)-3-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CN=C(N)C(C=2C=NC(=CC=2)C(F)(F)F)=N1 PXDXGCHQPAYYEN-UHFFFAOYSA-N 0.000 description 1
- WJPYCSQNYMMSQK-UHFFFAOYSA-N 5-(4-methylsulfonylphenyl)pyrazin-2-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CN=C(N)C=N1 WJPYCSQNYMMSQK-UHFFFAOYSA-N 0.000 description 1
- UAEQPLLFQAIGHI-UHFFFAOYSA-N 5-(4-propan-2-ylsulfonylphenyl)-3-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-amine Chemical compound C1=CC(S(=O)(=O)C(C)C)=CC=C1C1=CN=C(N)C(C=2C=NC(=CC=2)C(F)(F)F)=N1 UAEQPLLFQAIGHI-UHFFFAOYSA-N 0.000 description 1
- IKVDKCGDERAICR-UHFFFAOYSA-N 5-[4-(cyclopropylmethylsulfonyl)phenyl]-3-[6-(trifluoromethyl)pyridin-3-yl]pyrazin-2-amine Chemical compound NC1=NC=C(C=2C=CC(=CC=2)S(=O)(=O)CC2CC2)N=C1C1=CC=C(C(F)(F)F)N=C1 IKVDKCGDERAICR-UHFFFAOYSA-N 0.000 description 1
- DLYPREQTTOHKSM-UHFFFAOYSA-N 7-chloro-n-[[2-[(dimethylamino)methyl]cyclopenta-1,4-dien-1-yl]methyl]quinolin-4-amine;cyclopenta-1,3-diene;iron(2+) Chemical compound [Fe+2].C1C=CC=[C-]1.C1=[C-]CC(CN(C)C)=C1CNC1=CC=NC2=CC(Cl)=CC=C12 DLYPREQTTOHKSM-UHFFFAOYSA-N 0.000 description 1
- BRJULSXZDFYSPG-MSMJXPJBSA-N CC(C)(N)NC(=O)C[C@H]1CC[C@]2(CC1)OOC1(O2)[C@H]2CC3CC(C2)C[C@H]1C3 Chemical compound CC(C)(N)NC(=O)C[C@H]1CC[C@]2(CC1)OOC1(O2)[C@H]2CC3CC(C2)C[C@H]1C3 BRJULSXZDFYSPG-MSMJXPJBSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having 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
- C07D241/20—Nitrogen atoms
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- C07D401/10—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 carbon chain containing aromatic rings
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- 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
- C07D401/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261600324P | 2012-02-17 | 2012-02-17 | |
| US201261600324P | 2012-02-17 | ||
| PCT/IB2013/051235 WO2013121387A1 (en) | 2012-02-17 | 2013-02-15 | Anti -malarial agents |
Publications (1)
| Publication Number | Publication Date |
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| ES2589283T3 true ES2589283T3 (es) | 2016-11-11 |
Family
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| ES13712926.8T Active ES2589283T3 (es) | 2012-02-17 | 2013-02-15 | Agentes anti-malaria |
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| US (1) | US9266842B2 (enExample) |
| EP (1) | EP2814820B1 (enExample) |
| JP (1) | JP6226889B2 (enExample) |
| CN (1) | CN104136426B (enExample) |
| BR (1) | BR112014020212B1 (enExample) |
| CA (1) | CA2864483A1 (enExample) |
| CY (1) | CY1118074T1 (enExample) |
| DK (1) | DK2814820T3 (enExample) |
| ES (1) | ES2589283T3 (enExample) |
| HR (1) | HRP20161237T1 (enExample) |
| HU (1) | HUE029876T2 (enExample) |
| IN (1) | IN2014MN01622A (enExample) |
| LT (1) | LT2814820T (enExample) |
| ME (1) | ME02535B (enExample) |
| PL (1) | PL2814820T3 (enExample) |
| PT (1) | PT2814820T (enExample) |
| SI (1) | SI2814820T1 (enExample) |
| SM (1) | SMT201600441B (enExample) |
| WO (1) | WO2013121387A1 (enExample) |
| ZA (1) | ZA201406786B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2589283T3 (es) * | 2012-02-17 | 2016-11-11 | University Of Cape Town | Agentes anti-malaria |
| EP3118198A1 (en) | 2015-07-13 | 2017-01-18 | MMV Medicines for Malaria Venture | Anti-malarial agents |
| WO2017067881A1 (en) * | 2015-10-19 | 2017-04-27 | Glaxosmithkline Intellectual Property Development Limited | Pyrazine compounds for use in the treatment of parasitic protozoal infections |
| JP7057427B2 (ja) * | 2018-01-24 | 2022-04-19 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | 寄生虫感染の処置のための新規化合物 |
| CN112142715A (zh) * | 2020-10-10 | 2020-12-29 | 鲁南制药集团股份有限公司 | 一种2-氨基-5-杂环基取代的吡嗪衍生物及其用途 |
| WO2023094305A1 (en) * | 2021-11-23 | 2023-06-01 | Glaxosmithkline Intellectual Property Development Limited | Pyrazine compounds useful in the treatment of parasitic protozoal infection |
| CN119948032A (zh) | 2022-08-09 | 2025-05-06 | 默克专利股份有限公司 | 呋喃并嘧啶衍生物 |
| WO2024033280A1 (en) | 2022-08-09 | 2024-02-15 | Merck Patent Gmbh | Furopyridin and furopyrimidin, inhibitors of pi4k, for use in the treatment of parasite infection and malaria |
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| JP4772690B2 (ja) * | 2003-12-03 | 2011-09-14 | ワイエム・バイオサイエンシズ・オーストラリア・ピーティーワイ・リミテッド | チューブリン阻害剤 |
| ATE456565T1 (de) * | 2006-06-22 | 2010-02-15 | Biovitrum Ab Publ | Pyridin- und pyrazinderivate als mnk- kinaseinhibitoren |
| EP1900727A1 (en) * | 2006-08-30 | 2008-03-19 | Cellzome Ag | Aminopyridine derivatives as kinase inhibitors |
| GB0625659D0 (en) * | 2006-12-21 | 2007-01-31 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| EP2526090B1 (en) * | 2010-01-18 | 2015-08-19 | MMV Medicines for Malaria Venture | New anti-malarial agents |
| EP2569286B1 (en) * | 2010-05-12 | 2014-08-20 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| AU2012225805B2 (en) | 2011-03-04 | 2017-03-02 | Lexicon Pharmaceuticals, Inc. | MST1 kinase inhibitors and methods of their use |
| ES2589283T3 (es) * | 2012-02-17 | 2016-11-11 | University Of Cape Town | Agentes anti-malaria |
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2013
- 2013-02-15 ES ES13712926.8T patent/ES2589283T3/es active Active
- 2013-02-15 HU HUE13712926A patent/HUE029876T2/en unknown
- 2013-02-15 CN CN201380009373.9A patent/CN104136426B/zh not_active Expired - Fee Related
- 2013-02-15 US US14/379,332 patent/US9266842B2/en not_active Expired - Fee Related
- 2013-02-15 HR HRP20161237TT patent/HRP20161237T1/hr unknown
- 2013-02-15 EP EP13712926.8A patent/EP2814820B1/en active Active
- 2013-02-15 CA CA2864483A patent/CA2864483A1/en not_active Abandoned
- 2013-02-15 JP JP2014557157A patent/JP6226889B2/ja not_active Expired - Fee Related
- 2013-02-15 WO PCT/IB2013/051235 patent/WO2013121387A1/en not_active Ceased
- 2013-02-15 LT LTEP13712926.8T patent/LT2814820T/lt unknown
- 2013-02-15 PL PL13712926T patent/PL2814820T3/pl unknown
- 2013-02-15 IN IN1622MUN2014 patent/IN2014MN01622A/en unknown
- 2013-02-15 DK DK13712926.8T patent/DK2814820T3/en active
- 2013-02-15 SI SI201330290A patent/SI2814820T1/sl unknown
- 2013-02-15 PT PT137129268T patent/PT2814820T/pt unknown
- 2013-02-15 ME MEP-2016-214A patent/ME02535B/me unknown
- 2013-02-15 BR BR112014020212-5A patent/BR112014020212B1/pt not_active IP Right Cessation
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2014
- 2014-09-16 ZA ZA2014/06786A patent/ZA201406786B/en unknown
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2016
- 2016-10-10 CY CY20161100998T patent/CY1118074T1/el unknown
- 2016-12-02 SM SM201600441T patent/SMT201600441B/it unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SI2814820T1 (sl) | 2016-10-28 |
| PT2814820T (pt) | 2016-10-25 |
| HK1202859A1 (en) | 2015-10-09 |
| HRP20161237T1 (hr) | 2016-11-04 |
| BR112014020212B1 (pt) | 2021-11-23 |
| BR112014020212A8 (pt) | 2018-01-23 |
| CN104136426A (zh) | 2014-11-05 |
| HUE029876T2 (en) | 2017-04-28 |
| US20150031682A1 (en) | 2015-01-29 |
| EP2814820A1 (en) | 2014-12-24 |
| JP6226889B2 (ja) | 2017-11-08 |
| JP2015507004A (ja) | 2015-03-05 |
| WO2013121387A1 (en) | 2013-08-22 |
| US9266842B2 (en) | 2016-02-23 |
| CA2864483A1 (en) | 2013-08-22 |
| IN2014MN01622A (enExample) | 2015-05-15 |
| LT2814820T (lt) | 2016-10-25 |
| CY1118074T1 (el) | 2017-06-28 |
| ME02535B (me) | 2017-02-20 |
| EP2814820B1 (en) | 2016-07-20 |
| SMT201600441B (it) | 2017-01-10 |
| PL2814820T3 (pl) | 2017-01-31 |
| ZA201406786B (en) | 2015-06-24 |
| DK2814820T3 (en) | 2016-10-03 |
| CN104136426B (zh) | 2017-10-03 |
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