CA2307951A1 - Process for the synthesis of nucleoside analogs - Google Patents
Process for the synthesis of nucleoside analogs Download PDFInfo
- Publication number
- CA2307951A1 CA2307951A1 CA002307951A CA2307951A CA2307951A1 CA 2307951 A1 CA2307951 A1 CA 2307951A1 CA 002307951 A CA002307951 A CA 002307951A CA 2307951 A CA2307951 A CA 2307951A CA 2307951 A1 CA2307951 A1 CA 2307951A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- substituted
- dmso
- alkylidene
- heterocycle
- 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.)
- Abandoned
Links
- 239000002777 nucleoside Substances 0.000 title claims abstract description 99
- 238000000034 method Methods 0.000 title claims abstract description 78
- 150000003833 nucleoside derivatives Chemical class 0.000 title description 47
- 238000003786 synthesis reaction Methods 0.000 title description 23
- 230000015572 biosynthetic process Effects 0.000 title description 20
- 230000008569 process Effects 0.000 title description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 72
- 239000002798 polar solvent Substances 0.000 claims abstract description 28
- 230000000269 nucleophilic effect Effects 0.000 claims abstract description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 97
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
- 125000001072 heteroaryl group Chemical group 0.000 claims description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 36
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- 150000002243 furanoses Chemical class 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000012312 sodium hydride Substances 0.000 claims description 9
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 2
- 229910000105 potassium hydride Inorganic materials 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 239000011877 solvent mixture Substances 0.000 claims 2
- -1 furanosyl halide Chemical class 0.000 abstract description 72
- 238000005859 coupling reaction Methods 0.000 abstract description 16
- 230000008878 coupling Effects 0.000 abstract description 8
- 238000010168 coupling process Methods 0.000 abstract description 8
- 125000003835 nucleoside group Chemical group 0.000 abstract description 8
- 230000002194 synthesizing effect Effects 0.000 abstract description 5
- 238000006243 chemical reaction Methods 0.000 description 50
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000002585 base Substances 0.000 description 27
- 125000003342 alkenyl group Chemical group 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 22
- 125000000304 alkynyl group Chemical group 0.000 description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 238000013459 approach Methods 0.000 description 17
- 125000001424 substituent group Chemical group 0.000 description 15
- 235000000346 sugar Nutrition 0.000 description 15
- 229910001385 heavy metal Inorganic materials 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000005804 alkylation reaction Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- MBZCXOZTJSRAOQ-ZLUOBGJFSA-N (3as,4s,6as)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-ol Chemical compound C1O[C@H](O)[C@H]2OC(C)(C)O[C@H]21 MBZCXOZTJSRAOQ-ZLUOBGJFSA-N 0.000 description 6
- CCPHAMSKHBDMDS-UHFFFAOYSA-N Chetoseminudin B Natural products C=1NC2=CC=CC=C2C=1CC1(SC)NC(=O)C(CO)(SC)N(C)C1=O CCPHAMSKHBDMDS-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 5
- 125000001118 alkylidene group Chemical group 0.000 description 5
- 150000001450 anions Chemical class 0.000 description 5
- 125000003843 furanosyl group Chemical group 0.000 description 5
- 229960005235 piperonyl butoxide Drugs 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- OOXNYFKPOPJIOT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=12C(N)=NC=NC2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C1=CC=CC(Br)=C1 OOXNYFKPOPJIOT-UHFFFAOYSA-N 0.000 description 4
- 102100032534 Adenosine kinase Human genes 0.000 description 4
- 108010076278 Adenosine kinase Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 4
- 229910052753 mercury Inorganic materials 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WHPSMBYLYRPVGU-RFZPGFLSSA-N (3ar,6ar)-2,2-dimethyl-6,6a-dihydro-3ah-furo[3,4-d][1,3]dioxol-4-one Chemical compound C1OC(=O)[C@@H]2OC(C)(C)O[C@@H]21 WHPSMBYLYRPVGU-RFZPGFLSSA-N 0.000 description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 2
- IGHQOFUUDYGVMD-UHFFFAOYSA-N 1-methoxy-4-[[(4-methoxyphenyl)-diphenylmethoxy]-diphenylmethyl]benzene Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 IGHQOFUUDYGVMD-UHFFFAOYSA-N 0.000 description 2
- ARARQWKFKMWCDL-UHFFFAOYSA-N 1-nitro-2-[(2-nitrophenyl)methoxymethyl]benzene Chemical compound [O-][N+](=O)C1=CC=CC=C1COCC1=CC=CC=C1[N+]([O-])=O ARARQWKFKMWCDL-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 2
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 2
- 229910052684 Cerium Inorganic materials 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- DSLOWNUUMZVCAC-UHFFFAOYSA-N [dimethyl(propan-2-yl)silyl]oxy-dimethyl-propan-2-ylsilane Chemical compound CC(C)[Si](C)(C)O[Si](C)(C)C(C)C DSLOWNUUMZVCAC-UHFFFAOYSA-N 0.000 description 2
- XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 2
- 239000003121 adenosine kinase inhibitor Substances 0.000 description 2
- 229950006790 adenosine phosphate Drugs 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910052792 caesium Inorganic materials 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000005021 gait Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000004944 pyrrolopyrimidines Chemical class 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000013341 scale-up Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 2
- KJTULOVPMGUBJS-UHFFFAOYSA-N tert-butyl-[tert-butyl(diphenyl)silyl]oxy-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C(C)(C)C)O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 KJTULOVPMGUBJS-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- LGSAOJLQTXCYHF-UHFFFAOYSA-N tri(propan-2-yl)-tri(propan-2-yl)silyloxysilane Chemical compound CC(C)[Si](C(C)C)(C(C)C)O[Si](C(C)C)(C(C)C)C(C)C LGSAOJLQTXCYHF-UHFFFAOYSA-N 0.000 description 2
- DDCPKNYKNWXULB-RXMQYKEDSA-N (2r)-2-azaniumyl-3-[(2-methylpropan-2-yl)oxy]propanoate Chemical compound CC(C)(C)OC[C@@H]([NH3+])C([O-])=O DDCPKNYKNWXULB-RXMQYKEDSA-N 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 description 1
- YRCHYHRCBXNYNU-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide Chemical compound N1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC(F)=CC=4)=CC=3)F)=C2S1 YRCHYHRCBXNYNU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001828 phenalenyl group Chemical group C1(C=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- SRHXVXDPXODKQP-UHFFFAOYSA-N phosphinoline Chemical compound P1=CC=CC2=CC=CC=C21 SRHXVXDPXODKQP-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000001388 picenyl group Chemical group C1(=CC=CC2=CC=C3C4=CC=C5C=CC=CC5=C4C=CC3=C21)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 230000006824 pyrimidine synthesis Effects 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- JJJQHTCJNMSSJV-UHFFFAOYSA-N pyrrolo[2,3-d]pyrimidin-4-one Chemical compound O=C1N=CN=C2N=CC=C12 JJJQHTCJNMSSJV-UHFFFAOYSA-N 0.000 description 1
- XVHFAJKXXPJYDW-UHFFFAOYSA-N pyrrolo[3,2-d]pyrimidin-4-one Chemical class O=C1N=CN=C2C=CN=C12 XVHFAJKXXPJYDW-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- MABNMNVCOAICNO-UHFFFAOYSA-N selenophene Chemical compound C=1C=C[se]C=1 MABNMNVCOAICNO-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- TULWUZJYDBGXMY-UHFFFAOYSA-N tellurophene Chemical compound [Te]1C=CC=C1 TULWUZJYDBGXMY-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- BIQRTOBZAQMMOX-UHFFFAOYSA-N tert-butyl-(tert-butyl-methoxy-phenylsilyl)oxy-methoxy-phenylsilane Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(OC)O[Si](OC)(C(C)(C)C)C1=CC=CC=C1 BIQRTOBZAQMMOX-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- WILBTFWIBAOWLN-UHFFFAOYSA-N triethyl(triethylsilyloxy)silane Chemical compound CC[Si](CC)(CC)O[Si](CC)(CC)CC WILBTFWIBAOWLN-UHFFFAOYSA-N 0.000 description 1
- IVZTVZJLMIHPEY-UHFFFAOYSA-N triphenyl(triphenylsilyloxy)silane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C=1C=CC=CC=1)O[Si](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 IVZTVZJLMIHPEY-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
- 229940035893 uracil Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/14—Pyrrolo-pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13365199P | 1999-05-11 | 1999-05-11 | |
| US60/133,651 | 1999-05-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2307951A1 true CA2307951A1 (en) | 2000-11-11 |
Family
ID=22459680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002307951A Abandoned CA2307951A1 (en) | 1999-05-11 | 2000-05-09 | Process for the synthesis of nucleoside analogs |
Country Status (22)
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| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| PT1773856E (pt) * | 2004-07-21 | 2012-05-14 | Gilead Pharmasset Llc | Preparação de 2-desoxi-2-fluoro-d-ribofuranosilo pirimidinas e purinas substituídas com alquilo e seus derivados |
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| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| AU2006244195B2 (en) * | 2005-05-05 | 2012-03-15 | Ardea Biosciences, Inc. | Diaryl-purine, azapurines and -deazapurines as non-nucleoside reverse transcriptase inhibitors for treatment of HIV |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| US7994211B2 (en) | 2005-08-08 | 2011-08-09 | Argenta Discovery Limited | Bicyclo[2.2.1]hept-7-ylamine derivatives and their uses |
| PL2532679T3 (pl) | 2005-10-21 | 2017-09-29 | Novartis Ag | Ludzkie przeciwciała przeciwko IL13 i zastosowania terapeutyczne |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| RU2009115954A (ru) | 2006-09-29 | 2010-11-10 | Новартис АГ (CH) | Пиразолопиримидины в качестве ингибиторов липидной киназы р13к |
| KR20090075714A (ko) | 2006-10-30 | 2009-07-08 | 노파르티스 아게 | 소염제로서의 헤테로시클릭 화합물 |
| EP2229358B1 (en) | 2007-12-14 | 2011-03-23 | Pulmagen Therapeutics (Asthma) Limited | Indoles and their therapeutic use |
| WO2009079412A2 (en) | 2007-12-14 | 2009-06-25 | Ardea Biosciences Inc. | Reverse transcriptase inhibitors |
| WO2009087224A1 (en) | 2008-01-11 | 2009-07-16 | Novartis Ag | Pyrimidines as kinase inhibitors |
| EP2391366B1 (en) | 2009-01-29 | 2012-11-28 | Novartis AG | Substituted benzimidazoles for the treatment of astrocytomas |
| GB0902648D0 (en) | 2009-02-17 | 2009-04-01 | Argenta Discovery Ltd | Pharmaceutical compounds and compositions |
| BRPI1005327A2 (pt) | 2009-02-17 | 2019-09-24 | Chiesi Farm Spa | derivados de triazolopiridina como inibidores de p38 map quinase |
| US8927513B2 (en) * | 2009-07-07 | 2015-01-06 | Alnylam Pharmaceuticals, Inc. | 5′ phosphate mimics |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| JP5781510B2 (ja) | 2009-08-12 | 2015-09-24 | ノバルティス アーゲー | ヘテロ環式ヒドラゾン化合物および癌および炎症の処置のためのそれらの使用 |
| IN2012DN01961A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2009-08-17 | 2015-08-21 | Intellikine Llc | |
| JP5775871B2 (ja) | 2009-08-20 | 2015-09-09 | ノバルティス アーゲー | ヘテロ環式オキシム化合物 |
| GB201009731D0 (en) | 2010-06-10 | 2010-07-21 | Pulmagen Therapeutics Inflamma | Kinase inhibitors |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| JP2014505088A (ja) | 2011-02-10 | 2014-02-27 | ノバルティス アーゲー | Ｃ−ＭＥＴチロシンキナーゼ阻害剤としての［１，２，４］トリアゾロ［４，３−ｂ］ピリダジン化合物 |
| US9127000B2 (en) | 2011-02-23 | 2015-09-08 | Intellikine, LLC. | Heterocyclic compounds and uses thereof |
| AU2012220572A1 (en) | 2011-02-25 | 2013-08-29 | Irm Llc | Compounds and compositions as trk inhibitors |
| WO2013038362A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
| CN104363914A (zh) | 2011-11-23 | 2015-02-18 | 因特利凯有限责任公司 | 使用mTOR抑制剂的增强的治疗方案 |
| CN103987708B (zh) | 2011-12-09 | 2016-06-22 | 奇斯药制品公司 | 4-羟基-1,2,3,4-四氢萘-1-基脲的衍生物及其在呼吸道疾病治疗中的用途 |
| CA2858447C (en) | 2011-12-09 | 2020-10-27 | Monique Bodil Van Niel | Tryazolopyridine derivatives as kinase inhibitors |
| SG11201402986RA (en) | 2011-12-09 | 2014-12-30 | Chiesi Farma Spa | Kinase inhibitors |
| RU2660354C2 (ru) | 2012-04-03 | 2018-07-05 | Новартис Аг | Комбинированные продукты, содержащие ингибиторы тирозинкиназ, и их применение |
| CA2878054C (en) | 2012-06-29 | 2018-09-11 | Pfizer Inc. | Novel 4-(substituted-amino)-7h-pyrrolo[2,3-d]pyrimidines as lrrk2 inhibitors |
| CN105246482A (zh) | 2013-03-15 | 2016-01-13 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| EP3004097B1 (en) | 2013-06-06 | 2018-01-17 | Chiesi Farmaceutici S.p.A. | Kinase inhibitors |
| PE20161323A1 (es) | 2013-09-05 | 2016-11-25 | Hoffmann La Roche | Compuestos de triazolopiridina, composiciones y metodos de uso de los mismos |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| JP6487921B2 (ja) | 2013-12-17 | 2019-03-20 | ファイザー・インク | ＬＲＲＫ２阻害薬としての新規の３，４−二置換−１Ｈ−ピロロ［２，３−ｂ］ピリジンおよび４，５−二置換−７Ｈ−ピロロ［２，３−ｃ］ピリダジン |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
| ES2831416T3 (es) | 2014-07-31 | 2021-06-08 | Novartis Ag | Terapia de combinación de un inhibidor de MET y un inhibidor de EGFR |
| WO2016139212A1 (en) | 2015-03-04 | 2016-09-09 | F. Hoffmann-La Roche Ag | Triazolopyridine compounds and methods of use thereof |
| JP6873980B2 (ja) | 2015-09-14 | 2021-05-19 | ファイザー・インク | ＬＲＲＫ２阻害薬としての新規のイミダゾ［４，５−ｃ］キノリンおよびイミダゾ［４，５−ｃ］［１，５］ナフチリジン誘導体 |
| TW201720828A (zh) | 2015-11-23 | 2017-06-16 | 赫孚孟拉羅股份公司 | 治療性化合物及組合物以及其使用方法 |
| AR107164A1 (es) | 2015-12-23 | 2018-03-28 | Chiesi Farm Spa | INHIBIDORES DE QUINASA p38 |
| TW201730189A (zh) | 2015-12-23 | 2017-09-01 | 吉斯藥品公司 | 激酶抑制劑 |
| AR107163A1 (es) | 2015-12-23 | 2018-03-28 | Chiesi Farm Spa | Inhibidores de quinasa |
| EP3452464B1 (en) | 2016-05-05 | 2021-12-15 | F. Hoffmann-La Roche AG | Pyrazole derivatives, compositions and therapeutic use thereof |
| CR20190118A (es) | 2016-09-06 | 2019-04-30 | Hoffmann La Roche | COMPUESTOS 8-(AZETIDIN-1-IL)-[1,2,4]TRIAZOLO[1,5-a]PIRIDINILO, COMPOSICIONES Y MÉTODOS DE UTILIZACIPON DE LOS MISMOS |
| CN110114343B (zh) | 2016-12-29 | 2022-09-06 | 豪夫迈·罗氏有限公司 | 吡唑并嘧啶化合物及其使用方法 |
| JP2020510061A (ja) | 2017-03-14 | 2020-04-02 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | ピラゾロクロロフェニル化合物、組成物及びその使用方法 |
| CN110678467B (zh) | 2017-05-22 | 2023-06-13 | 豪夫迈·罗氏有限公司 | 治疗化合物和组合物及其使用方法 |
| WO2018215389A1 (en) | 2017-05-22 | 2018-11-29 | F. Hoffmann-La Roche Ag | Therapeutic compounds and compositions, and methods of use thereof |
| US10364245B2 (en) | 2017-06-07 | 2019-07-30 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| WO2019139714A1 (en) | 2018-01-15 | 2019-07-18 | Genentech, Inc. | Pyrazolopyrimidine compounds as jak inhibitors |
| CA3102279A1 (en) | 2018-06-01 | 2019-12-05 | Cornell University | Combination therapy for pi3k-associated disease or disorder |
| MA56518A (fr) | 2019-06-18 | 2022-04-27 | Hoffmann La Roche | Inhibiteurs de sulfone pyrazolopyrimidine de jak kinases et leurs utilisations |
| TW202115069A (zh) | 2019-06-18 | 2021-04-16 | 瑞士商赫孚孟拉羅股份公司 | Ｊａｋ激酶之經四唑取代之吡唑并嘧啶抑制劑及其用途 |
| JP7716993B2 (ja) | 2019-06-18 | 2025-08-01 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | Ｊａｋキナーゼのピラゾロピリミジンアリールエーテル阻害剤及びその使用 |
| TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法 |
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| JPS61207400A (ja) * | 1985-03-11 | 1986-09-13 | Nippon Zoki Pharmaceut Co Ltd | ヌクレオシド化合物の製造方法 |
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| US4859677A (en) | 1987-04-17 | 1989-08-22 | University Of Kansas | Nucleoside analogues having antiviral activity |
| US5246931A (en) | 1988-10-25 | 1993-09-21 | Bristol-Myers Squibb Company | Carbocyclic nucleoside analogs |
| US5688778A (en) | 1989-05-15 | 1997-11-18 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Nucleoside analogs |
| GB8916480D0 (en) | 1989-07-19 | 1989-09-06 | Glaxo Group Ltd | Chemical process |
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| US5726302A (en) * | 1989-09-15 | 1998-03-10 | Gensia Inc. | Water soluble adenosine kinase inhibitors |
| US5763596A (en) | 1989-09-15 | 1998-06-09 | Metabasis Therapeutics, Inc. | C-4' modified adenosine kinase inhibitors |
| US5276151A (en) | 1990-02-01 | 1994-01-04 | Emory University | Method of synthesis of 1,3-dioxolane nucleosides |
| US5470857A (en) | 1990-09-14 | 1995-11-28 | Marion Merrell Dow Inc. | Carbocyclic nucleoside analogs useful as immunosuppressants |
| SE9003151D0 (sv) | 1990-10-02 | 1990-10-02 | Medivir Ab | Nucleoside derivatives |
| ZA923641B (en) | 1991-05-21 | 1993-02-24 | Iaf Biochem Int | Processes for the diastereoselective synthesis of nucleosides |
| GB9204015D0 (en) | 1992-02-25 | 1992-04-08 | Wellcome Found | Therapeutic nucleosides |
| TW374087B (en) | 1993-05-25 | 1999-11-11 | Univ Yale | L-2',3'-dideoxy nucleotide analogs as anti-hepatitis B(HBV) and anti-HIV agents |
| AU3086495A (en) * | 1994-08-02 | 1996-03-04 | Banyu Pharmaceutical Co., Ltd. | Antitumor indolopyrrolocarbazoles |
| US5659023A (en) | 1995-02-01 | 1997-08-19 | Gilead Sciences, Inc. | Nucleotide analogues |
| TR199801431T2 (xx) | 1996-01-23 | 1998-10-21 | The Regents Of The University Of Michigan | Antiviral aktif maddeler olarak de�i�tirilmi� benzimidazol n�kleosidler. |
-
2000
- 2000-05-03 YU YU25500A patent/YU25500A/sh unknown
- 2000-05-08 IL IL13602700A patent/IL136027A0/xx unknown
- 2000-05-08 IN IN421MU2000 patent/IN186850B/en unknown
- 2000-05-08 US US09/566,468 patent/US6271370B1/en not_active Expired - Fee Related
- 2000-05-09 CA CA002307951A patent/CA2307951A1/en not_active Abandoned
- 2000-05-09 DE DE60018833T patent/DE60018833D1/de not_active Expired - Lifetime
- 2000-05-09 AR ARP000102222A patent/AR028991A1/es active IP Right Grant
- 2000-05-09 EP EP00303892A patent/EP1052264B1/en not_active Expired - Lifetime
- 2000-05-09 JP JP2000135874A patent/JP2001011092A/ja active Pending
- 2000-05-09 AT AT00303892T patent/ATE291582T1/de not_active IP Right Cessation
- 2000-05-09 ZA ZA200002263A patent/ZA200002263B/xx unknown
- 2000-05-09 BR BR0002089-3A patent/BR0002089A/pt not_active IP Right Cessation
- 2000-05-10 ID IDP20000389D patent/ID25992A/id unknown
- 2000-05-10 AU AU34011/00A patent/AU3401100A/en not_active Abandoned
- 2000-05-10 RU RU2000111438/04A patent/RU2200738C2/ru not_active IP Right Cessation
- 2000-05-10 MX MXPA00004532A patent/MXPA00004532A/es unknown
- 2000-05-10 HU HU0001843A patent/HUP0001843A3/hu unknown
- 2000-05-10 CN CN00107145A patent/CN1275575A/zh active Pending
- 2000-05-10 KR KR10-2000-0024885A patent/KR100403900B1/ko not_active Expired - Fee Related
- 2000-05-10 CZ CZ20001710A patent/CZ20001710A3/cs unknown
- 2000-05-11 TR TR2000/01340A patent/TR200001340A2/xx unknown
- 2000-05-11 PL PL00340109A patent/PL340109A1/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IL136027A0 (en) | 2001-05-20 |
| US6271370B1 (en) | 2001-08-07 |
| ATE291582T1 (de) | 2005-04-15 |
| MXPA00004532A (es) | 2002-03-08 |
| HUP0001843A3 (en) | 2001-09-28 |
| AU3401100A (en) | 2000-11-16 |
| JP2001011092A (ja) | 2001-01-16 |
| HUP0001843A2 (hu) | 2001-06-28 |
| KR100403900B1 (ko) | 2003-11-01 |
| EP1052264A2 (en) | 2000-11-15 |
| HU0001843D0 (en) | 2000-07-28 |
| DE60018833D1 (de) | 2005-04-28 |
| IN186850B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2001-11-24 |
| ID25992A (id) | 2000-11-16 |
| YU25500A (sh) | 2003-08-29 |
| ZA200002263B (en) | 2001-12-24 |
| TR200001340A2 (tr) | 2000-12-21 |
| EP1052264A3 (en) | 2001-06-13 |
| BR0002089A (pt) | 2001-01-02 |
| KR20010069193A (ko) | 2001-07-23 |
| PL340109A1 (en) | 2000-11-20 |
| AR028991A1 (es) | 2003-06-04 |
| RU2200738C2 (ru) | 2003-03-20 |
| EP1052264B1 (en) | 2005-03-23 |
| CZ20001710A3 (cs) | 2001-09-12 |
| CN1275575A (zh) | 2000-12-06 |
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