DE60036102T2 - Purinderivate, verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen - Google Patents
Purinderivate, verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen Download PDFInfo
- Publication number
- DE60036102T2 DE60036102T2 DE60036102T DE60036102T DE60036102T2 DE 60036102 T2 DE60036102 T2 DE 60036102T2 DE 60036102 T DE60036102 T DE 60036102T DE 60036102 T DE60036102 T DE 60036102T DE 60036102 T2 DE60036102 T2 DE 60036102T2
- Authority
- DE
- Germany
- Prior art keywords
- amino
- cyclopentyl
- trans
- formula
- aminocyclohexyl
- 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 - Fee Related
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- 238000000034 method Methods 0.000 title claims description 80
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 5
- 150000003212 purines Chemical class 0.000 title description 5
- 238000004519 manufacturing process Methods 0.000 title description 3
- -1 phenyl radicals Chemical class 0.000 claims description 170
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 93
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 91
- 238000006243 chemical reaction Methods 0.000 claims description 69
- 125000004432 carbon atom Chemical group C* 0.000 claims description 56
- 150000003254 radicals Chemical class 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 22
- 239000011707 mineral Substances 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 18
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical compound O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 13
- 150000007513 acids Chemical class 0.000 claims description 12
- 150000007524 organic acids Chemical class 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 150000007530 organic bases Chemical class 0.000 claims description 10
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 235000005985 organic acids Nutrition 0.000 claims description 9
- 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 claims description 8
- 125000003158 alcohol group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- KGIJGLXKUAZPFM-MXVIHJGJSA-N CCOC(=O)c1cc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCCC2)cc(c1)C(=O)OCC Chemical compound CCOC(=O)c1cc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCCC2)cc(c1)C(=O)OCC KGIJGLXKUAZPFM-MXVIHJGJSA-N 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 150000002148 esters Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000004001 thioalkyl group Chemical group 0.000 claims description 6
- NTEQWEGVDVAKPN-NTPOMRHGSA-N CCOC(=O)c1ccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCSC2)cc1 Chemical compound CCOC(=O)c1ccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCSC2)cc1 NTEQWEGVDVAKPN-NTPOMRHGSA-N 0.000 claims description 5
- QZRPIDMTLGJZFA-IYARVYRRSA-N CCOC(=O)c1cccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCCC2)c1 Chemical compound CCOC(=O)c1cccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCCC2)c1 QZRPIDMTLGJZFA-IYARVYRRSA-N 0.000 claims description 5
- 241000233866 Fungi Species 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 150000003457 sulfones Chemical class 0.000 claims description 4
- 150000003462 sulfoxides Chemical class 0.000 claims description 4
- WZUNHASDFCXWMZ-UAPYVXQJSA-N CCOC(=O)c1ccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCCC2)cc1 Chemical compound CCOC(=O)c1ccc(Nc2nc(N[C@H]3CC[C@H](N)CC3)nc3n(cnc23)C2CCCC2)cc1 WZUNHASDFCXWMZ-UAPYVXQJSA-N 0.000 claims description 3
- 230000002555 anti-neurodegenerative effect Effects 0.000 claims description 3
- 239000003080 antimitotic agent Substances 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 230000009223 neuronal apoptosis Effects 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 150000002923 oximes Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 claims description 2
- 230000006909 anti-apoptosis Effects 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 238000003776 cleavage reaction Methods 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 230000001537 neural effect Effects 0.000 claims description 2
- 244000045947 parasite Species 0.000 claims description 2
- 230000007017 scission Effects 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims 2
- 208000030852 Parasitic disease Diseases 0.000 claims 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 239000000047 product Substances 0.000 description 549
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 396
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 372
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 318
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 272
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 258
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 232
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 178
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 152
- 239000000377 silicon dioxide Substances 0.000 description 129
- 239000003480 eluent Substances 0.000 description 113
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 110
- 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 98
- VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical compound NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 description 97
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
- 239000013078 crystal Substances 0.000 description 87
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 83
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 77
- 235000011114 ammonium hydroxide Nutrition 0.000 description 77
- 239000000243 solution Substances 0.000 description 77
- 239000002904 solvent Substances 0.000 description 77
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 74
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 65
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 61
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 57
- 238000000746 purification Methods 0.000 description 56
- 230000002829 reductive effect Effects 0.000 description 52
- 238000003756 stirring Methods 0.000 description 47
- 238000004587 chromatography analysis Methods 0.000 description 42
- 238000001704 evaporation Methods 0.000 description 39
- 230000008020 evaporation Effects 0.000 description 38
- 239000011780 sodium chloride Substances 0.000 description 38
- 229920006395 saturated elastomer Polymers 0.000 description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 28
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 21
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 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 16
- 238000001035 drying Methods 0.000 description 16
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 14
- 238000005191 phase separation Methods 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 230000009471 action Effects 0.000 description 11
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 11
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 10
- 108091007914 CDKs Proteins 0.000 description 9
- 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
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
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- 239000000203 mixture Substances 0.000 description 9
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- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
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- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical class OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 7
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
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- GIZCKBSSWNIUMZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(CN)C=C1 GIZCKBSSWNIUMZ-UHFFFAOYSA-N 0.000 description 7
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- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
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- 238000007254 oxidation reaction Methods 0.000 description 6
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- PWKCQUTXTGYNIS-JCNLHEQBSA-N N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(N)cc2)c2ncn(C3CCCC3)c2n1 Chemical compound N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(N)cc2)c2ncn(C3CCCC3)c2n1 PWKCQUTXTGYNIS-JCNLHEQBSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical group 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
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- 235000019260 propionic acid Nutrition 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
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 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
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000036633 rest Effects 0.000 description 1
- 238000007127 saponification reaction 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
- 229910052708 sodium Inorganic materials 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
- 239000000126 substance Substances 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- JNMRHUJNCSQMMB-UHFFFAOYSA-N sulfathiazole Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CS1 JNMRHUJNCSQMMB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000001117 sulphuric acid Substances 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 238000010792 warming Methods 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 (3)
| 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 |
| FR9906456 | 1999-05-21 | ||
| 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 |
|---|---|
| DE60036102D1 DE60036102D1 (de) | 2007-10-04 |
| DE60036102T2 true DE60036102T2 (de) | 2008-05-15 |
Family
ID=9545846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60036102T Expired - Fee Related DE60036102T2 (de) | 1999-05-21 | 2000-05-18 | Purinderivate, verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen |
Country Status (33)
| Country | Link |
|---|---|
| US (2) | US7122669B1 (OSRAM) |
| EP (1) | EP1183256B1 (OSRAM) |
| JP (1) | JP2003500407A (OSRAM) |
| KR (1) | KR100707895B1 (OSRAM) |
| CN (1) | CN1298719C (OSRAM) |
| AP (1) | AP1477A (OSRAM) |
| AR (1) | AR035317A1 (OSRAM) |
| AT (1) | ATE370951T1 (OSRAM) |
| AU (1) | AU4764500A (OSRAM) |
| BR (1) | BR0011282A (OSRAM) |
| CA (1) | CA2374714A1 (OSRAM) |
| CZ (1) | CZ20014163A3 (OSRAM) |
| DE (1) | DE60036102T2 (OSRAM) |
| DK (1) | DK1183256T3 (OSRAM) |
| DZ (1) | DZ3166A1 (OSRAM) |
| EA (1) | EA005072B1 (OSRAM) |
| ES (1) | ES2290033T3 (OSRAM) |
| FR (1) | FR2793794B1 (OSRAM) |
| HU (1) | HUP0201649A3 (OSRAM) |
| IL (1) | IL146441A0 (OSRAM) |
| MA (1) | MA26791A1 (OSRAM) |
| MX (1) | MXPA01011834A (OSRAM) |
| NO (1) | NO20015659L (OSRAM) |
| NZ (1) | NZ515556A (OSRAM) |
| PL (1) | PL352293A1 (OSRAM) |
| PT (1) | PT1183256E (OSRAM) |
| SK (1) | SK16722001A3 (OSRAM) |
| TR (1) | TR200103349T2 (OSRAM) |
| TW (1) | TWI284130B (OSRAM) |
| UA (1) | UA68441C2 (OSRAM) |
| WO (1) | WO2000071543A1 (OSRAM) |
| YU (1) | YU86601A (OSRAM) |
| ZA (1) | ZA200109602B (OSRAM) |
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 |
| US6667311B2 (en) * | 2001-09-11 | 2003-12-23 | Albany Molecular Research, Inc. | Nitrogen substituted biaryl purine derivatives as potent antiproliferative agents |
| US6812232B2 (en) | 2001-09-11 | 2004-11-02 | Amr Technology, Inc. | Heterocycle substituted purine derivatives as potent antiproliferative agents |
| 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 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
1999
- 1999-05-21 FR FR9906456A patent/FR2793794B1/fr not_active Expired - Fee Related
-
2000
- 2000-05-09 TW TW089108817A patent/TWI284130B/zh not_active IP Right Cessation
- 2000-05-18 EP EP00929625A patent/EP1183256B1/fr not_active Expired - Lifetime
- 2000-05-18 AT AT00929625T patent/ATE370951T1/de not_active IP Right Cessation
- 2000-05-18 AU AU47645/00A patent/AU4764500A/en not_active Abandoned
- 2000-05-18 CA CA002374714A patent/CA2374714A1/fr not_active Abandoned
- 2000-05-18 PT PT00929625T patent/PT1183256E/pt unknown
- 2000-05-18 SK SK1672-2001A patent/SK16722001A3/sk unknown
- 2000-05-18 KR KR1020017014800A patent/KR100707895B1/ko not_active Expired - Fee Related
- 2000-05-18 DE DE60036102T patent/DE60036102T2/de not_active Expired - Fee Related
- 2000-05-18 UA UA2001128864A patent/UA68441C2/uk unknown
- 2000-05-18 IL IL14644100A patent/IL146441A0/xx unknown
- 2000-05-18 TR TR2001/03349T patent/TR200103349T2/xx unknown
- 2000-05-18 PL PL00352293A patent/PL352293A1/xx not_active Application Discontinuation
- 2000-05-18 WO PCT/FR2000/001335 patent/WO2000071543A1/fr not_active Ceased
- 2000-05-18 EA EA200101224A patent/EA005072B1/ru not_active IP Right Cessation
- 2000-05-18 US US09/979,389 patent/US7122669B1/en not_active Expired - Fee Related
- 2000-05-18 ES ES00929625T patent/ES2290033T3/es not_active Expired - Lifetime
- 2000-05-18 DZ DZ003166A patent/DZ3166A1/xx active
- 2000-05-18 NZ NZ515556A patent/NZ515556A/en unknown
- 2000-05-18 HU HU0201649A patent/HUP0201649A3/hu unknown
- 2000-05-18 YU YU86601A patent/YU86601A/sh unknown
- 2000-05-18 DK DK00929625T patent/DK1183256T3/da active
- 2000-05-18 CZ CZ20014163A patent/CZ20014163A3/cs unknown
- 2000-05-18 BR BR0011282-8A patent/BR0011282A/pt not_active Application Discontinuation
- 2000-05-18 AP APAP/P/2001/002355A patent/AP1477A/en active
- 2000-05-18 CN CNB008106509A patent/CN1298719C/zh not_active Expired - Fee Related
- 2000-05-18 JP JP2000619799A patent/JP2003500407A/ja not_active Abandoned
- 2000-05-18 MX MXPA01011834A patent/MXPA01011834A/es active IP Right Grant
- 2000-05-19 AR ARP000102428A patent/AR035317A1/es not_active Application Discontinuation
-
2001
- 2001-11-15 MA MA26410A patent/MA26791A1/fr unknown
- 2001-11-20 NO NO20015659A patent/NO20015659L/no not_active Application Discontinuation
- 2001-11-21 ZA ZA200109602A patent/ZA200109602B/xx unknown
-
2004
- 2004-12-07 US US11/006,013 patent/US7208598B2/en not_active Expired - Fee Related
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| 8339 | Ceased/non-payment of the annual fee |