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
- FNQJDLTXOVEEFB-UHFFFAOYSA-N 1,2,3-benzothiadiazole Chemical compound C1=CC=C2SN=NC2=C1 FNQJDLTXOVEEFB-UHFFFAOYSA-N 0.000 description 1
- ITFCEERPJPLHPQ-UHFFFAOYSA-N 1,3-dichloro-2-[(2,6-dichlorophenyl)methoxymethyl]benzene Chemical compound ClC1=CC=CC(Cl)=C1COCC1=C(Cl)C=CC=C1Cl ITFCEERPJPLHPQ-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- GAHRWPUTGHCERR-UHFFFAOYSA-N 1-[bis(2-chloroethoxy)methoxy-(2-chloroethoxy)methoxy]-2-chloroethane Chemical compound ClCCOC(OCCCl)OC(OCCCl)OCCCl GAHRWPUTGHCERR-UHFFFAOYSA-N 0.000 description 1
- PPJVXZVTPWQOQS-UHFFFAOYSA-N 1-ethoxy-1-(1-ethoxyethoxy)ethane Chemical compound CCOC(C)OC(C)OCC PPJVXZVTPWQOQS-UHFFFAOYSA-N 0.000 description 1
- GPAAEZIXSQCCES-UHFFFAOYSA-N 1-methoxy-2-(2-methoxyethoxymethoxymethoxy)ethane Chemical compound COCCOCOCOCCOC GPAAEZIXSQCCES-UHFFFAOYSA-N 0.000 description 1
- CBDLNOVOFXJEOB-UHFFFAOYSA-N 1-methoxy-4-(4-methoxyphenoxy)benzene Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(OC)C=C1 CBDLNOVOFXJEOB-UHFFFAOYSA-N 0.000 description 1
- SDTORDSXCYSNTD-UHFFFAOYSA-N 1-methoxy-4-[(4-methoxyphenyl)methoxymethyl]benzene Chemical compound C1=CC(OC)=CC=C1COCC1=CC=C(OC)C=C1 SDTORDSXCYSNTD-UHFFFAOYSA-N 0.000 description 1
- VJJRVNGOHNKPHB-UHFFFAOYSA-N 1-nitro-4-[(4-nitrophenyl)methoxymethyl]benzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1COCC1=CC=C([N+]([O-])=O)C=C1 VJJRVNGOHNKPHB-UHFFFAOYSA-N 0.000 description 1
- YVZGLPYJHZGRBY-UHFFFAOYSA-N 1-phenyl-4-[(4-phenylphenyl)methoxymethyl]benzene Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1COCC(C=C1)=CC=C1C1=CC=CC=C1 YVZGLPYJHZGRBY-UHFFFAOYSA-N 0.000 description 1
- MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
- AAQTWLBJPNLKHT-UHFFFAOYSA-N 1H-perimidine Chemical compound N1C=NC2=CC=CC3=CC=CC1=C32 AAQTWLBJPNLKHT-UHFFFAOYSA-N 0.000 description 1
- ODMMNALOCMNQJZ-UHFFFAOYSA-N 1H-pyrrolizine Chemical compound C1=CC=C2CC=CN21 ODMMNALOCMNQJZ-UHFFFAOYSA-N 0.000 description 1
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 description 1
- HSTWBXXEIFNPOG-UHFFFAOYSA-N 2,3-dihydro-1H-arsindole Chemical compound [AsH]1CCC2=CC=CC=C12 HSTWBXXEIFNPOG-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- COEVUTZPOGDNRY-UHFFFAOYSA-N 2-(1,3-benzodithiol-2-yloxy)-1,3-benzodithiole Chemical compound S1C2=CC=CC=C2SC1OC1SC2=CC=CC=C2S1 COEVUTZPOGDNRY-UHFFFAOYSA-N 0.000 description 1
- CALZWRITFOWNNV-UHFFFAOYSA-N 2-(2-phenylselanylethoxy)ethylselanylbenzene Chemical compound C=1C=CC=CC=1[Se]CCOCC[Se]C1=CC=CC=C1 CALZWRITFOWNNV-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- YFEXZJKJPFNYKB-UHFFFAOYSA-N 2-(oxolan-2-yloxy)oxolane Chemical compound C1CCOC1OC1OCCC1 YFEXZJKJPFNYKB-UHFFFAOYSA-N 0.000 description 1
- GBWMWHHLQDBPFP-UHFFFAOYSA-N 2-(thian-2-yloxy)thiane Chemical compound S1CCCCC1OC1SCCCC1 GBWMWHHLQDBPFP-UHFFFAOYSA-N 0.000 description 1
- JMTBNBFBHBCERV-UHFFFAOYSA-N 2-(thiolan-2-yloxy)thiolane Chemical compound C1CCSC1OC1SCCC1 JMTBNBFBHBCERV-UHFFFAOYSA-N 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- DTCYSRAEJHGSNY-UHFFFAOYSA-N 2-methoxy-2-(2-methoxypropan-2-yloxy)propane Chemical compound COC(C)(C)OC(C)(C)OC DTCYSRAEJHGSNY-UHFFFAOYSA-N 0.000 description 1
- MSVSJBJSJCKNJD-UHFFFAOYSA-N 2H-isoarsindole Chemical compound C1=CC=CC2=C[AsH]C=C21 MSVSJBJSJCKNJD-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 1
- JTSSUEWTRDWHGY-UHFFFAOYSA-N 4-(pyridin-4-ylmethoxymethyl)pyridine Chemical compound C=1C=NC=CC=1COCC1=CC=NC=C1 JTSSUEWTRDWHGY-UHFFFAOYSA-N 0.000 description 1
- KTFBMMKWTQVUIV-UHFFFAOYSA-N 4-[(3,4-dimethoxyphenyl)methoxymethyl]-1,2-dimethoxybenzene Chemical compound C1=C(OC)C(OC)=CC=C1COCC1=CC=C(OC)C(OC)=C1 KTFBMMKWTQVUIV-UHFFFAOYSA-N 0.000 description 1
- GYAVWCQUWMBKPL-UHFFFAOYSA-N 4-[(4-cyanophenyl)methoxymethyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1COCC1=CC=C(C#N)C=C1 GYAVWCQUWMBKPL-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- ZQVMXWDQXLWKLE-UHFFFAOYSA-N 4-methoxy-2-(4-methoxyoxan-2-yl)oxyoxane Chemical compound C1C(OC)CCOC1OC1OCCC(OC)C1 ZQVMXWDQXLWKLE-UHFFFAOYSA-N 0.000 description 1
- ZXTCTDQZUWWAEY-UHFFFAOYSA-N 4-methoxy-2-(4-methoxythian-2-yl)oxythiane Chemical compound C1C(OC)CCSC1OC1SCCC(OC)C1 ZXTCTDQZUWWAEY-UHFFFAOYSA-N 0.000 description 1
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- INFWBGQYCBUADA-UHFFFAOYSA-N 9-anthracen-9-yloxyanthracene Chemical compound C1=CC=C2C(OC=3C4=CC=CC=C4C=C4C=CC=CC4=3)=C(C=CC=C3)C3=CC2=C1 INFWBGQYCBUADA-UHFFFAOYSA-N 0.000 description 1
- BPMFPOGUJAAYHL-UHFFFAOYSA-N 9H-Pyrido[2,3-b]indole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=N1 BPMFPOGUJAAYHL-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 239000005964 Acibenzolar-S-methyl Substances 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- LMADLNJFWANXNP-UHFFFAOYSA-N C1=CC=C2NC(P(=O)=O)=CC2=C1 Chemical compound C1=CC=C2NC(P(=O)=O)=CC2=C1 LMADLNJFWANXNP-UHFFFAOYSA-N 0.000 description 1
- ASKLQCSOQWQVST-UHFFFAOYSA-N C1=[As]C=CC2=CC=CC=C12 Chemical compound C1=[As]C=CC2=CC=CC=C12 ASKLQCSOQWQVST-UHFFFAOYSA-N 0.000 description 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-isoascorbic acid Chemical compound OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 1
- 241000380126 Gymnosteris Species 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- PVQATPQSBYNMGE-UHFFFAOYSA-N [benzhydryloxy(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)C1=CC=CC=C1 PVQATPQSBYNMGE-UHFFFAOYSA-N 0.000 description 1
- KWSUZUAUJVMRAE-UHFFFAOYSA-N [diethyl(propan-2-yl)silyl]oxy-diethyl-propan-2-ylsilane Chemical compound CC[Si](CC)(C(C)C)O[Si](CC)(CC)C(C)C KWSUZUAUJVMRAE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- KUQYFTVHQPWHPP-UHFFFAOYSA-N acridarsine Chemical group C1=CC=CC2=[As]C3=CC=CC=C3C=C12 KUQYFTVHQPWHPP-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- JYFGNSGDZQOMBE-UHFFFAOYSA-N arsanthridine Chemical compound C1=CC=CC2=[As]C=C3C=CC=CC3=C12 JYFGNSGDZQOMBE-UHFFFAOYSA-N 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- BVUSIQTYUVWOSX-UHFFFAOYSA-N arsindole Chemical compound C1=CC=C2[As]C=CC2=C1 BVUSIQTYUVWOSX-UHFFFAOYSA-N 0.000 description 1
- 229930190922 arsindoline Natural products 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- LJWBIAMZBJWAOW-UHFFFAOYSA-N benzhydryloxysilane Chemical compound C=1C=CC=CC=1C(O[SiH3])C1=CC=CC=C1 LJWBIAMZBJWAOW-UHFFFAOYSA-N 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- 125000002676 chrysenyl group Chemical group C1(=CC=CC=2C3=CC=C4C=CC=CC4=C3C=CC12)* 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 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 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 235000010350 erythorbic acid Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 125000006038 hexenyl group Chemical group 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
- LOBVCQUMXHOALK-UHFFFAOYSA-N hexyl-[hexyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CCCCCC[Si](C)(C)O[Si](C)(C)CCCCCC LOBVCQUMXHOALK-UHFFFAOYSA-N 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000003427 indacenyl group Chemical group 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229940026239 isoascorbic acid Drugs 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
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 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
- ODZILJDRJCJHKM-UHFFFAOYSA-N isophosphinoline Chemical compound C1=PC=CC2=CC=CC=C21 ODZILJDRJCJHKM-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 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)
| Country | Link |
|---|---|
| US (1) | US6271370B1 (show.php) |
| EP (1) | EP1052264B1 (show.php) |
| JP (1) | JP2001011092A (show.php) |
| KR (1) | KR100403900B1 (show.php) |
| CN (1) | CN1275575A (show.php) |
| AR (1) | AR028991A1 (show.php) |
| AT (1) | ATE291582T1 (show.php) |
| AU (1) | AU3401100A (show.php) |
| BR (1) | BR0002089A (show.php) |
| CA (1) | CA2307951A1 (show.php) |
| CZ (1) | CZ20001710A3 (show.php) |
| DE (1) | DE60018833D1 (show.php) |
| HU (1) | HUP0001843A3 (show.php) |
| ID (1) | ID25992A (show.php) |
| IL (1) | IL136027A0 (show.php) |
| IN (1) | IN186850B (show.php) |
| MX (1) | MXPA00004532A (show.php) |
| PL (1) | PL340109A1 (show.php) |
| RU (1) | RU2200738C2 (show.php) |
| TR (1) | TR200001340A2 (show.php) |
| YU (1) | YU25500A (show.php) |
| ZA (1) | ZA200002263B (show.php) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200519106A (en) | 2003-05-02 | 2005-06-16 | Novartis Ag | Organic compounds |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| ES2386005T3 (es) * | 2004-07-21 | 2012-08-07 | Gilead Pharmasset Llc | Preparación de 2-desoxi-2-fluoro-d-ribofuranosil pirimidinas y purinas sustituidas con alquilo y sus derivados |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| ES2380951T3 (es) * | 2005-05-05 | 2012-05-21 | Ardea Biosciences, Inc. | Diaril-purinas, -azapurinasy - desazapurinas como inhibidores no nucleósidos de la transcriptasa inversa para el tratamiento del VIH |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| EP1924553A1 (en) | 2005-08-08 | 2008-05-28 | Argenta Discovery Limited | Bicyclo[2.2.]hept-7-ylamine derivatives and their uses |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| CA2625664C (en) | 2005-10-21 | 2016-01-05 | Novartis Ag | Human antibodies against il13 and therapeutic uses |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| AU2007302263A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as P13K lipid kinase inhibitors |
| WO2008052734A1 (en) | 2006-10-30 | 2008-05-08 | Novartis Ag | Heterocyclic compounds as antiinflammatory agents |
| WO2009079412A2 (en) * | 2007-12-14 | 2009-06-25 | Ardea Biosciences Inc. | Reverse transcriptase inhibitors |
| EP2327693B9 (en) | 2007-12-14 | 2012-10-24 | Pulmagen Therapeutics (Asthma) Limited | Indoles and their therapeutic use |
| JP5584138B2 (ja) | 2008-01-11 | 2014-09-03 | ノバルティス アーゲー | キナーゼ阻害剤としてのピリミジン類 |
| SI2391366T1 (sl) | 2009-01-29 | 2013-01-31 | Novartis Ag | Substituirani benzimidazoli za zdravljenje astrocitomov |
| GB0902648D0 (en) | 2009-02-17 | 2009-04-01 | Argenta Discovery Ltd | Pharmaceutical compounds and compositions |
| PE20120655A1 (es) | 2009-02-17 | 2012-06-07 | Chiesi Farma Spa | Derivados de triazolopiridina como inhibidores de proteinas cinasas activadas por mitogeno p38 (map) |
| WO2011005860A2 (en) * | 2009-07-07 | 2011-01-13 | 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 |
| KR20120089643A (ko) | 2009-08-12 | 2012-08-13 | 노파르티스 아게 | 헤테로시클릭 히드라존 화합물, 및 암 및 염증을 치료하기 위한 그의 용도 |
| US9085560B2 (en) | 2009-08-17 | 2015-07-21 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
| 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 |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| EP2673277A1 (en) | 2011-02-10 | 2013-12-18 | Novartis AG | [1, 2, 4]triazolo [4, 3 -b]pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| JP5808826B2 (ja) | 2011-02-23 | 2015-11-10 | インテリカイン， エルエルシー | 複素環化合物およびその使用 |
| CA2828219A1 (en) | 2011-02-25 | 2012-08-30 | Irm Llc | Pyrazolo [1,5-a] pyridines as trk inhibitors |
| US9062045B2 (en) | 2011-09-15 | 2015-06-23 | Novartis Ag | Triazolopyridine compounds |
| US20130209543A1 (en) | 2011-11-23 | 2013-08-15 | Intellikine Llc | Enhanced treatment regimens using mtor inhibitors |
| RU2586333C1 (ru) | 2011-12-09 | 2016-06-10 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Производные 4-гидрокси-1,2,3,4-тетрагидронафталин-1-ил-мочевины и их применение в лечении, среди прочего, заболеваний дыхательного тракта |
| MX351958B (es) | 2011-12-09 | 2017-11-06 | Chiesi Farm Spa | Inhibidores de cinasa. |
| WO2013083604A1 (en) | 2011-12-09 | 2013-06-13 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| ES2894830T3 (es) | 2012-04-03 | 2022-02-16 | Novartis Ag | Productos combinados con inhibidores de tirosina·cinasa y su uso |
| CA2878054C (en) | 2012-06-29 | 2018-09-11 | Pfizer Inc. | Novel 4-(substituted-amino)-7h-pyrrolo[2,3-d]pyrimidines as lrrk2 inhibitors |
| WO2014151147A1 (en) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
| AR096532A1 (es) | 2013-06-06 | 2016-01-13 | Chiesi Farm Spa | Inhibidores de quinasa |
| CN105745209B (zh) | 2013-09-05 | 2018-10-23 | 豪夫迈·罗氏有限公司 | 三唑并吡啶化合物、组合物及其使用方法 |
| WO2015084804A1 (en) | 2013-12-03 | 2015-06-11 | Novartis Ag | Combination of mdm2 inhibitor and braf inhibitor and their use |
| 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 |
| KR20170036037A (ko) | 2014-07-31 | 2017-03-31 | 노파르티스 아게 | 조합 요법 |
| EP3265464A1 (en) | 2015-03-04 | 2018-01-10 | F. Hoffmann-La Roche AG | Triazolopyridine compounds and methods of use thereof |
| WO2017046675A1 (en) | 2015-09-14 | 2017-03-23 | Pfizer Inc. | Novel imidazo [4,5-c] quinoline and imidazo [4,5-c][1,5] naphthyridine derivatives as lrrk2 inhibitors |
| 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 |
| AR107163A1 (es) | 2015-12-23 | 2018-03-28 | Chiesi Farm Spa | Inhibidores de quinasa |
| WO2017108737A1 (en) | 2015-12-23 | 2017-06-29 | Chiesi Farmaceutici S.P.A. | 1-(3-tert-butyl-phenyl)-3-(4-([1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro- naphthalen-1-yl)-urea derivatives and their use as p38 mapk inhibitors |
| EP3452464B1 (en) | 2016-05-05 | 2021-12-15 | F. Hoffmann-La Roche AG | Pyrazole derivatives, compositions and therapeutic use thereof |
| SG11201901954XA (en) | 2016-09-06 | 2019-04-29 | Hoffmann La Roche | 8-(azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyridinyl compounds, compositions and methods of use thereof |
| AU2017385543A1 (en) | 2016-12-29 | 2019-05-23 | F. Hoffmann-La Roche Ag | Pyrazolopyrimidine compounds and methods of use thereof |
| WO2018166993A2 (en) | 2017-03-14 | 2018-09-20 | F. Hoffmann-La Roche Ag | Pyrazolochlorophenyl compounds, compositions and methods of use thereof |
| EP3630767A1 (en) | 2017-05-22 | 2020-04-08 | H. Hoffnabb-La Roche Ag | Therapeutic compounds and compositions, and methods of use thereof |
| KR20200010390A (ko) | 2017-05-22 | 2020-01-30 | 에프. 호프만-라 로슈 아게 | 치료 화합물 및 조성물, 및 이의 사용 방법 |
| US10364245B2 (en) | 2017-06-07 | 2019-07-30 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| JP7339263B2 (ja) | 2018-01-15 | 2023-09-05 | エフ． ホフマン－ラ ロシュ アーゲー | Ｊａｋ阻害剤としてのピラゾロピリミジン化合物 |
| CA3102279A1 (en) | 2018-06-01 | 2019-12-05 | Cornell University | Combination therapy for pi3k-associated disease or disorder |
| JP7657740B2 (ja) | 2019-06-18 | 2025-04-07 | 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スルホン阻害剤およびその使用 |
| EP3986899A1 (en) | 2019-06-18 | 2022-04-27 | F. Hoffmann-La Roche AG | Pyrazolopyrimidine aryl ether inhibitors of jak kinases and uses thereof |
| 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 |
| 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 |
| CN117343119A (zh) * | 2022-06-29 | 2024-01-05 | 上海交通大学 | 一种烷基化核苷、核苷酸、寡核苷酸及其类似物的制备方法 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US4751292A (en) | 1985-07-02 | 1988-06-14 | The Plant Cell Research Institute, Inc. | Adamantyl purines |
| 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 |
| US5763596A (en) | 1989-09-15 | 1998-06-09 | Metabasis Therapeutics, Inc. | C-4' modified adenosine kinase inhibitors |
| US5674998A (en) | 1989-09-15 | 1997-10-07 | Gensia Inc. | C-4' modified adenosine kinase inhibitors |
| US5726302A (en) * | 1989-09-15 | 1998-03-10 | Gensia Inc. | Water soluble 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 |
| BR9707185A (pt) | 1996-01-23 | 1999-03-23 | Glaxo Group Ltd | Nucleosídeos de benzimidazol modificados como agentes antivirais |
-
2000
- 2000-05-03 YU YU25500A patent/YU25500A/sh 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
- 2000-05-08 IL IL13602700A patent/IL136027A0/xx unknown
- 2000-05-09 BR BR0002089-3A patent/BR0002089A/pt not_active IP Right Cessation
- 2000-05-09 DE DE60018833T patent/DE60018833D1/de not_active Expired - Lifetime
- 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 JP JP2000135874A patent/JP2001011092A/ja active Pending
- 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 CA CA002307951A patent/CA2307951A1/en not_active Abandoned
- 2000-05-10 HU HU0001843A patent/HUP0001843A3/hu unknown
- 2000-05-10 CN CN00107145A patent/CN1275575A/zh active Pending
- 2000-05-10 CZ CZ20001710A patent/CZ20001710A3/cs unknown
- 2000-05-10 AU AU34011/00A patent/AU3401100A/en not_active Abandoned
- 2000-05-10 ID IDP20000389D patent/ID25992A/id unknown
- 2000-05-10 MX MXPA00004532A patent/MXPA00004532A/es unknown
- 2000-05-10 RU RU2000111438/04A patent/RU2200738C2/ru not_active IP Right Cessation
- 2000-05-10 KR KR10-2000-0024885A patent/KR100403900B1/ko not_active Expired - Fee Related
- 2000-05-11 PL PL00340109A patent/PL340109A1/xx not_active Application Discontinuation
- 2000-05-11 TR TR2000/01340A patent/TR200001340A2/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR100403900B1 (ko) | 2003-11-01 |
| KR20010069193A (ko) | 2001-07-23 |
| US6271370B1 (en) | 2001-08-07 |
| EP1052264A2 (en) | 2000-11-15 |
| EP1052264A3 (en) | 2001-06-13 |
| IL136027A0 (en) | 2001-05-20 |
| JP2001011092A (ja) | 2001-01-16 |
| ATE291582T1 (de) | 2005-04-15 |
| HUP0001843A3 (en) | 2001-09-28 |
| HU0001843D0 (en) | 2000-07-28 |
| EP1052264B1 (en) | 2005-03-23 |
| BR0002089A (pt) | 2001-01-02 |
| TR200001340A2 (tr) | 2000-12-21 |
| IN186850B (show.php) | 2001-11-24 |
| RU2200738C2 (ru) | 2003-03-20 |
| CN1275575A (zh) | 2000-12-06 |
| ZA200002263B (en) | 2001-12-24 |
| YU25500A (sh) | 2003-08-29 |
| HUP0001843A2 (hu) | 2001-06-28 |
| CZ20001710A3 (cs) | 2001-09-12 |
| DE60018833D1 (de) | 2005-04-28 |
| PL340109A1 (en) | 2000-11-20 |
| AR028991A1 (es) | 2003-06-04 |
| MXPA00004532A (es) | 2002-03-08 |
| AU3401100A (en) | 2000-11-16 |
| ID25992A (id) | 2000-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1052264B1 (en) | Process for the synthesis of nucleoside analogs | |
| CN107613990B (zh) | 烟酰胺单核苷酸的有效合成 | |
| KR101995598B1 (ko) | 부분입체 이성질성으로 순수한 포스포라미데이트 전구약물의 제조 방법 | |
| CA2496698C (en) | 5-h-pyrrolo[3,2-d]pyrimidine inhibitors of nucleoside phosphorylases and nucleosidases | |
| RU2116306C1 (ru) | Пиримидин-нуклеозиды, способы их получения, фармацевтическая композиция | |
| WO2011003018A9 (en) | Halogenated 2-deoxy-lactones, 2'-deoxy--nucleosides, and derivatives thereof | |
| US4968690A (en) | 3-deazaneplanocin, intermediates for it, and antiviral composition and method of treatment using it | |
| KR102485731B1 (ko) | Jak 효소 억제제 및 이의 제조 방법과 용도 | |
| IE904070A1 (en) | Deoxyfluoronucleoside process | |
| Rahim et al. | Synthesis and biological properties of 2′-deoxy-5-vinyluridine and 2′-deoxy-5-vinylcytidine | |
| Hocková et al. | Synthesis and cytostatic activity of nucleosides and acyclic nucleoside analogues derived from 6-(trifluoromethyl) purines | |
| WO2007047793A2 (en) | Cyclopentenol nucleoside compounds, intermediates for their synthesis and methods of treating viral infections | |
| Seela et al. | Synthesis of 6-Substituted 7-Carbapurine 2′, 3′-Dideoxynucleosides: Solid-Liquid Phase-Transfer Glycosylation of 4-Chloropyrrolo [2, 3-d] pyrimidine and Deoxygenation of its 2′-Deoxyribofuranoside | |
| Minakawa et al. | Nucleosides and nucleotides. 116. Convenient syntheses of 3-deazaadenosine, 3-deazaguanosine, and 3-deazainosine via ring closure of 5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide or-carbonitrile | |
| Hancox et al. | Some reactions of 4′-thionucleosides and their sulfones | |
| Zhang et al. | Palladium-Mediated Coupling Reactions of an Aminosubstituted Heterocycle. Direct Synthesis of C-Nucleosides Related to Adenosine | |
| IE922192A1 (en) | Cycloalkyltriols containing cyclic substituents, processes¹and intermediate products for their preparation and their¹use as antiviral and antiparasitic agents | |
| Nauš et al. | Cytostatic and antiviral 6-arylpurine ribonucleosides IX. synthesis and evaluation of 6-substituted 3-deazapurine ribonucleosides | |
| EP3983393A1 (en) | Novel spirobicyclic intermediates | |
| Chudinov et al. | A new effective method for the synthesis of 1, 2, 4-triazole-3-carboxamide and ribavirin derivatives | |
| Gopalakrishnan et al. | Regioselective 2′/3′-O-Allylation of Pyrimidine Ribonucleosides Using Phase Transfer Catalysis | |
| CN103788160A (zh) | (2r,5r)-5-磷酰甲氧基-2-(2-取代腺嘌呤-9-基)- 2,5-二氢呋喃核苷类似物及其制备方法和用途 | |
| US3826803A (en) | Arabinofuranosyl-8-azaadenines | |
| HK1033138A (en) | Process for the synthesis of nucleoside analogs | |
| MXPA03011298A (es) | Compuestos 5'-nor-1-homo-n-carbonucleosidos y proceso de obtencion de los mismos. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |