EA005072B1 - Производные пурина, способ их получения и содержащие их фармацевтические композиции - Google Patents
Производные пурина, способ их получения и содержащие их фармацевтические композиции Download PDFInfo
- Publication number
- EA005072B1 EA005072B1 EA200101224A EA200101224A EA005072B1 EA 005072 B1 EA005072 B1 EA 005072B1 EA 200101224 A EA200101224 A EA 200101224A EA 200101224 A EA200101224 A EA 200101224A EA 005072 B1 EA005072 B1 EA 005072B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- formula
- radical
- alkyl
- compound
- carbon atoms
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 5
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 5
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title description 2
- -1 -CH2- heterocyclic Chemical group 0.000 claims abstract description 577
- 150000001875 compounds Chemical class 0.000 claims abstract description 341
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 157
- 150000003254 radicals Chemical class 0.000 claims abstract description 146
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 95
- 150000003839 salts Chemical class 0.000 claims abstract description 94
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 86
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 44
- 125000003118 aryl group Chemical group 0.000 claims abstract description 42
- 239000002253 acid Substances 0.000 claims abstract description 40
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 40
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 40
- 125000005843 halogen group Chemical group 0.000 claims abstract description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 37
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 34
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims abstract description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 26
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 26
- 239000011707 mineral Substances 0.000 claims abstract description 26
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 26
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 25
- 150000007524 organic acids Chemical class 0.000 claims abstract description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 22
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 20
- 235000005985 organic acids Nutrition 0.000 claims abstract description 19
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 18
- 150000007530 organic bases Chemical class 0.000 claims abstract description 18
- 125000004429 atom Chemical group 0.000 claims abstract description 17
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 150000005840 aryl radicals Chemical class 0.000 claims abstract description 16
- 239000001301 oxygen Substances 0.000 claims abstract description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 12
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims abstract description 9
- YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 6
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 6
- 125000004001 thioalkyl group Chemical group 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 125000001422 pyrrolinyl group Chemical group 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract 2
- 150000002367 halogens Chemical class 0.000 claims abstract 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 202
- 239000000203 mixture Substances 0.000 claims description 186
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 138
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 83
- 238000006243 chemical reaction Methods 0.000 claims description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
- 238000005755 formation reaction Methods 0.000 claims description 41
- 230000015572 biosynthetic process Effects 0.000 claims description 32
- 125000006239 protecting group Chemical group 0.000 claims description 31
- 230000003993 interaction Effects 0.000 claims description 29
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 20
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 18
- 238000006722 reduction reaction Methods 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 17
- 125000003158 alcohol group Chemical group 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 238000007254 oxidation reaction Methods 0.000 claims description 14
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 14
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 13
- 150000002576 ketones Chemical group 0.000 claims description 13
- 230000009466 transformation Effects 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 11
- 150000002148 esters Chemical group 0.000 claims description 11
- 150000007513 acids Chemical class 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 239000005711 Benzoic acid Substances 0.000 claims description 9
- 150000001299 aldehydes Chemical class 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 8
- 150000003462 sulfoxides Chemical class 0.000 claims description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 8
- 208000030852 Parasitic disease Diseases 0.000 claims description 7
- 235000010233 benzoic acid Nutrition 0.000 claims description 7
- 238000003776 cleavage reaction Methods 0.000 claims description 7
- 238000005886 esterification reaction Methods 0.000 claims description 7
- 125000004494 ethyl ester group Chemical group 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 150000002923 oximes Chemical group 0.000 claims description 7
- 238000007127 saponification reaction Methods 0.000 claims description 7
- 150000003457 sulfones Chemical class 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 150000002828 nitro derivatives Chemical class 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003080 antimitotic agent Substances 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 230000009223 neuronal apoptosis Effects 0.000 claims description 4
- 238000000844 transformation Methods 0.000 claims description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
- LKMOGYXCKJCDQJ-GJFNAKTISA-N Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(cc2)C#N)c2ncn(C3CCCC3)c2n1 Chemical compound Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(cc2)C#N)c2ncn(C3CCCC3)c2n1 LKMOGYXCKJCDQJ-GJFNAKTISA-N 0.000 claims description 3
- 241000233866 Fungi Species 0.000 claims description 3
- 230000002555 anti-neurodegenerative effect Effects 0.000 claims description 3
- 230000001028 anti-proliverative effect Effects 0.000 claims description 3
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 3
- QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 claims description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 3
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 3
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims description 2
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 230000002538 fungal effect Effects 0.000 claims description 2
- 239000012948 isocyanate Substances 0.000 claims description 2
- 150000002513 isocyanates Chemical class 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical compound [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims 2
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 claims 2
- 208000031361 Hiccup Diseases 0.000 claims 1
- 239000007983 Tris buffer Substances 0.000 claims 1
- 230000009257 reactivity Effects 0.000 claims 1
- JEVCWSUVFOYBFI-UHFFFAOYSA-N cyanyl Chemical compound N#[C] JEVCWSUVFOYBFI-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 abstract description 2
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 abstract 3
- 229910006069 SO3H Inorganic materials 0.000 abstract 3
- 239000000654 additive Substances 0.000 abstract 3
- 230000000996 additive effect Effects 0.000 abstract 3
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 abstract 1
- 229910006074 SO2NH2 Inorganic materials 0.000 abstract 1
- 239000000047 product Substances 0.000 description 433
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 382
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 357
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 299
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 243
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 193
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 184
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 157
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 154
- 239000000741 silica gel Substances 0.000 description 129
- 229910002027 silica gel Inorganic materials 0.000 description 129
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 128
- 239000003480 eluent Substances 0.000 description 117
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 111
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 110
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 100
- VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical compound NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 description 97
- 239000013078 crystal Substances 0.000 description 94
- 239000000243 solution Substances 0.000 description 80
- 239000002904 solvent Substances 0.000 description 77
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 71
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 71
- 235000011114 ammonium hydroxide Nutrition 0.000 description 71
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- 238000000746 purification Methods 0.000 description 55
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 54
- 230000002829 reductive effect Effects 0.000 description 50
- 238000004587 chromatography analysis Methods 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000007864 aqueous solution Substances 0.000 description 31
- 239000011780 sodium chloride Substances 0.000 description 19
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 18
- 238000010438 heat treatment Methods 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 13
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 12
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 235000010755 mineral Nutrition 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- 230000009471 action Effects 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 10
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- UETQVDZZPKAQIC-UHFFFAOYSA-N chlorane Chemical compound Cl.Cl.Cl.Cl UETQVDZZPKAQIC-UHFFFAOYSA-N 0.000 description 9
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 9
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
- 238000006482 condensation reaction Methods 0.000 description 6
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- DWGWCWDDNTVOGF-UHFFFAOYSA-N Cl.Cl.Cl.Cl.Cl.Cl Chemical compound Cl.Cl.Cl.Cl.Cl.Cl DWGWCWDDNTVOGF-UHFFFAOYSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- UDSRUCAJZSIRHZ-UHFFFAOYSA-N benzamide dihydrochloride Chemical compound Cl.Cl.NC(=O)C1=CC=CC=C1.NC(=O)C1=CC=CC=C1 UDSRUCAJZSIRHZ-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000007654 immersion Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
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- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 125000002720 diazolyl group Chemical group 0.000 description 1
- GVVOANLKCBPVIR-UHFFFAOYSA-N diethyl 5-[(2-chloro-9-cyclopentylpurin-6-yl)amino]benzene-1,3-dicarboxylate Chemical compound CCOC(=O)C1=CC(C(=O)OCC)=CC(NC=2C=3N=CN(C=3N=C(Cl)N=2)C2CCCC2)=C1 GVVOANLKCBPVIR-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 230000000547 effect on apoptosis Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- POODNGNSOOXMBJ-UHFFFAOYSA-N ethyl 2-[2-[(2-chloro-9-cyclopentylpurin-6-yl)amino]ethylsulfamoyl]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1S(=O)(=O)NCCNC1=NC(Cl)=NC2=C1N=CN2C1CCCC1 POODNGNSOOXMBJ-UHFFFAOYSA-N 0.000 description 1
- WMQPVNIQYJAKBL-UHFFFAOYSA-N ethyl 2-[4-[(2-chloro-9-cyclopentylpurin-6-yl)amino]phenyl]acetate Chemical compound C(C)OC(CC1=CC=C(C=C1)NC1=C2N=CN(C2=NC(=N1)Cl)C1CCCC1)=O WMQPVNIQYJAKBL-UHFFFAOYSA-N 0.000 description 1
- YYVLJSYHJIQREA-UHFFFAOYSA-N ethyl 2-chlorosulfonylbenzoate Chemical compound CCOC(=O)C1=CC=CC=C1S(Cl)(=O)=O YYVLJSYHJIQREA-UHFFFAOYSA-N 0.000 description 1
- FLJFADSWIOZIAZ-UHFFFAOYSA-N ethyl 3-[(2-chloro-9-cyclopentylpurin-6-yl)amino]benzoate Chemical compound CCOC(=O)C1=CC=CC(NC=2C=3N=CN(C=3N=C(Cl)N=2)C2CCCC2)=C1 FLJFADSWIOZIAZ-UHFFFAOYSA-N 0.000 description 1
- GADPHXAWEODQPA-UHFFFAOYSA-N ethyl 4-[[2-chloro-9-(thiolan-3-yl)purin-6-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC1=NC(Cl)=NC2=C1N=CN2C1CSCC1 GADPHXAWEODQPA-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
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- 239000012535 impurity Substances 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- OPUAWDUYWRUIIL-UHFFFAOYSA-N methanedisulfonic acid Chemical compound OS(=O)(=O)CS(O)(=O)=O OPUAWDUYWRUIIL-UHFFFAOYSA-N 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- HUNUAFNLLYVTQD-UHFFFAOYSA-N methyl 2-chlorosulfonylbenzoate Chemical compound COC(=O)C1=CC=CC=C1S(Cl)(=O)=O HUNUAFNLLYVTQD-UHFFFAOYSA-N 0.000 description 1
- PZIFZFDZDLEJLO-UHFFFAOYSA-N methyl 4-[[(2-chloro-9-cyclopentylpurin-6-yl)amino]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CNC1=NC(Cl)=NC2=C1N=CN2C1CCCC1 PZIFZFDZDLEJLO-UHFFFAOYSA-N 0.000 description 1
- FEIOASZZURHTHB-UHFFFAOYSA-N methyl 4-formylbenzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
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- WFAKXKVHHXGZIJ-UHFFFAOYSA-N n'-(2-chloro-9-cyclopentylpurin-6-yl)benzenesulfonohydrazide Chemical compound C=12N=CN(C3CCCC3)C2=NC(Cl)=NC=1NNS(=O)(=O)C1=CC=CC=C1 WFAKXKVHHXGZIJ-UHFFFAOYSA-N 0.000 description 1
- RHOAHBLVHCUZBB-UHFFFAOYSA-N n'-(2-chloro-9-cyclopentylpurin-6-yl)ethane-1,2-diamine Chemical compound C1=NC=2C(NCCN)=NC(Cl)=NC=2N1C1CCCC1 RHOAHBLVHCUZBB-UHFFFAOYSA-N 0.000 description 1
- AJWNYPNPXLNRAO-UHFFFAOYSA-N n-(1,3-thiazol-2-yl)benzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)NC1=NC=CS1 AJWNYPNPXLNRAO-UHFFFAOYSA-N 0.000 description 1
- SLDBXMFBOFIMAL-UHFFFAOYSA-N n-[2-[(2-chloro-9-cyclopentylpurin-6-yl)amino]ethyl]-1,1,1-trifluoromethanesulfonamide Chemical compound C1=NC=2C(NCCNS(=O)(=O)C(F)(F)F)=NC(Cl)=NC=2N1C1CCCC1 SLDBXMFBOFIMAL-UHFFFAOYSA-N 0.000 description 1
- FDVYDUFKGKTROA-UHFFFAOYSA-N n-[2-[[2-[(4-aminocyclohexyl)amino]-9-cyclopentylpurin-6-yl]amino]ethyl]-3,5-dichlorobenzamide;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCC1NC1=NC(NCCNC(=O)C=2C=C(Cl)C=C(Cl)C=2)=C(N=CN2C3CCCC3)C2=N1 FDVYDUFKGKTROA-UHFFFAOYSA-N 0.000 description 1
- OPTWHQOHFRXUEQ-UHFFFAOYSA-N n-[2-[[2-[(4-aminocyclohexyl)amino]-9-cyclopentylpurin-6-yl]amino]ethyl]-4-(trifluoromethyl)benzamide;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCC1NC1=NC(NCCNC(=O)C=2C=CC(=CC=2)C(F)(F)F)=C(N=CN2C3CCCC3)C2=N1 OPTWHQOHFRXUEQ-UHFFFAOYSA-N 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- SEVSMVUOKAMPDO-UHFFFAOYSA-N para-Acetoxybenzaldehyde Natural products CC(=O)OC1=CC=C(C=O)C=C1 SEVSMVUOKAMPDO-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- RUOPINZRYMFPBF-UHFFFAOYSA-N pentane-1,3-diol Chemical compound CCC(O)CCO RUOPINZRYMFPBF-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- WZHRJGWXUCLILI-UHFFFAOYSA-N sulfonylcarbamic acid Chemical compound OC(=O)N=S(=O)=O WZHRJGWXUCLILI-UHFFFAOYSA-N 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
- BJYXNFYVCZIXQC-UHFFFAOYSA-N thiolan-3-ol Chemical compound OC1CCSC1 BJYXNFYVCZIXQC-UHFFFAOYSA-N 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/24—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one nitrogen and one sulfur atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Psychiatry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9906456A FR2793794B1 (fr) | 1999-05-21 | 1999-05-21 | Nouveaux derives de la purine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation |
| PCT/FR2000/001335 WO2000071543A1 (fr) | 1999-05-21 | 2000-05-18 | Derives de la purine, leur procede de preparation, et compositions pharmaceutiques les contenant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200101224A1 EA200101224A1 (ru) | 2002-10-31 |
| EA005072B1 true EA005072B1 (ru) | 2004-10-28 |
Family
ID=9545846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200101224A EA005072B1 (ru) | 1999-05-21 | 2000-05-18 | Производные пурина, способ их получения и содержащие их фармацевтические композиции |
Country Status (33)
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6413974B1 (en) * | 1998-02-26 | 2002-07-02 | Aventis Pharmaceuticals Inc. | 6,9,-disubstituted 2-[trans-(4-aminocyclohexyl) amino] purines |
| US6479487B1 (en) * | 1998-02-26 | 2002-11-12 | Aventis Pharmaceuticals Inc. | 6, 9-disubstituted 2-[trans-(4-aminocyclohexyl)amino] purines |
| US6969720B2 (en) | 1999-03-17 | 2005-11-29 | Amr Technology, Inc. | Biaryl substituted purine derivatives as potent antiproliferative agents |
| US6861524B2 (en) * | 2000-10-31 | 2005-03-01 | Aventis Pharmaceuticals Inc. | Acyl and sulfonyl derivatives of 6,9-disubstituted 2-(trans-1,4-diaminocyclohexyl)-purines and their use as antiproliferative agents |
| ATE426603T1 (de) * | 2000-10-31 | 2009-04-15 | Aventis Pharma Inc | Acyl- und sulfonylderivative 6,9- disubstitutierter 2-(trans-1,4-diaminocyclohexyl)-purine und ihre verwendung als antiproliferative mittel |
| FR2818642B1 (fr) * | 2000-12-26 | 2005-07-15 | Hoechst Marion Roussel Inc | Nouveaux derives de la purine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilistion |
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| CA2463563A1 (en) * | 2001-10-12 | 2003-04-17 | Irm Llc | Kinase inhibitor scaffolds and methods for their preparation |
| EP1556129A4 (en) * | 2002-10-15 | 2011-02-09 | Irm Llc | COMPOSITIONS AND METHODS OF INDUCING OSTEOGENESIS |
| FR2851248B1 (fr) * | 2003-02-18 | 2005-04-08 | Aventis Pharma Sa | Nouveaux derives de la purine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation |
| ES2398239T3 (es) | 2003-11-10 | 2013-03-14 | The Scripps Research Institute | Composiciones y procedimientos para inducir la desdiferenciación celular |
| AU2005231440B9 (en) * | 2004-04-02 | 2012-02-23 | Dogwood Pharmaceuticals, Inc. | Selective antagonists of A2A adenosine receptors |
| CZ302122B6 (cs) * | 2009-01-28 | 2010-10-20 | Univerzita Palackého v Olomouci | Substituované deriváty 6-(2-aminobenzylamino)purinu, jejich použití jako léciva a prípravky tyto slouceniny obsahující |
| WO2012142029A2 (en) | 2011-04-10 | 2012-10-18 | Florida A&M University | Serms for the treatment of estrogen receptor-mediated disorders |
| EP3134405B1 (en) | 2014-04-25 | 2019-08-28 | Pfizer Inc | Heteroaromatic compounds and their use as dopamine d1 ligands |
| CN114149432B (zh) * | 2016-09-30 | 2024-07-05 | 斯坦福国际研究院 | 用于癌症治疗的双重clk/cdk1抑制剂 |
| CZ308029B6 (cs) | 2017-03-20 | 2019-11-06 | Univerzita PalackĂ©ho v Olomouci | 2,6-Disubstituované-9-cyklopentyl-9H-puriny, jejich použití jako léčiva a farmaceutické přípravky |
| WO2024127350A1 (en) | 2022-12-16 | 2024-06-20 | Astrazeneca Ab | 2,6,9-trisubstituted purines |
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| DE4008858A1 (de) * | 1990-03-20 | 1991-09-26 | Hoechst Ag | Substituierte purine, verfahren zu ihrer hertellung sowie ihre verwendung als antivirale mittel |
| EP0841810B1 (en) * | 1991-12-05 | 2000-06-21 | Texas Instruments Incorporated | Method to improve a video signal |
| CA2084222C (en) * | 1991-12-06 | 2004-04-06 | David R. Borcherding | Novel trans cyclopentanyl purine analogs useful as immunosuppressants |
| DE69627195T2 (de) * | 1995-11-01 | 2004-01-29 | Novartis Ag | Purinderivate und verfahren zu ihrer herstellung |
| FR2741881B1 (fr) * | 1995-12-01 | 1999-07-30 | Centre Nat Rech Scient | Nouveaux derives de purine possedant notamment des prorietes anti-proliferatives et leurs applications biologiques |
| US5866702A (en) * | 1996-08-02 | 1999-02-02 | Cv Therapeutics, Incorporation | Purine inhibitors of cyclin dependent kinase 2 |
| US6790958B2 (en) * | 1996-08-02 | 2004-09-14 | Robert T. Lum | Purine inhibitors of cyclin dependent kinase 2 & IKBA |
| WO1998016528A1 (en) * | 1996-10-11 | 1998-04-23 | Chiron Corporation | Purine inhibitors of glycogen synthase kinase 3 (gsk3) |
| AU735127B2 (en) * | 1997-08-07 | 2001-06-28 | Regents Of The University Of California, The | Purine inhibitor of protein kinases, G proteins and polymerases |
| US6413974B1 (en) * | 1998-02-26 | 2002-07-02 | Aventis Pharmaceuticals Inc. | 6,9,-disubstituted 2-[trans-(4-aminocyclohexyl) amino] purines |
| US6479487B1 (en) * | 1998-02-26 | 2002-11-12 | Aventis Pharmaceuticals Inc. | 6, 9-disubstituted 2-[trans-(4-aminocyclohexyl)amino] purines |
| GB9903762D0 (en) * | 1999-02-18 | 1999-04-14 | Novartis Ag | Organic compounds |
| FR2818642B1 (fr) * | 2000-12-26 | 2005-07-15 | Hoechst Marion Roussel Inc | Nouveaux derives de la purine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilistion |
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