NO326625B1 - Syntese av 2-aralkoksyadenosiner og 2-alkoksyadenosiner - Google Patents

Syntese av 2-aralkoksyadenosiner og 2-alkoksyadenosiner Download PDF

Info

Publication number: NO326625B1
Authority: NO; Norway
Prior art keywords: procedure according; group; solvent; amine; hours
Prior art date: 2001-10-25

Application number

NO20042126A

Other languages

English (en)

Norwegian (no)

Other versions

NO20042126L (no

Inventor

Allan Ray Moorman

Original Assignee

King Pharmaceuticals Res & Dev

Priority date (The priority date 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 date listed.)

2001-10-25

Filing date

2004-05-24

Publication date

2009-01-19

2004-05-24 Application filed by King Pharmaceuticals Res & Dev filed Critical King Pharmaceuticals Res & Dev

2004-06-23 Publication of NO20042126L publication Critical patent/NO20042126L/no

2009-01-19 Publication of NO326625B1 publication Critical patent/NO326625B1/no

Links

238000003786 synthesis reaction Methods 0.000 title description 10
230000015572 biosynthetic process Effects 0.000 title description 9
238000000034 method Methods 0.000 claims description 69
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 57
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 56
150000001875 compounds Chemical class 0.000 claims description 45
239000002904 solvent Substances 0.000 claims description 45
238000006243 chemical reaction Methods 0.000 claims description 38
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 31
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
-1 alkyl nitrite Chemical compound 0.000 claims description 30
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 28
230000035484 reaction time Effects 0.000 claims description 28
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 26
238000002360 preparation method Methods 0.000 claims description 25
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 25
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 22
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 17
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 16
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 16
125000003118 aryl group Chemical group 0.000 claims description 16
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 16
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 16
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 16
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 14
239000002168 alkylating agent Substances 0.000 claims description 14
229940100198 alkylating agent Drugs 0.000 claims description 14
229910021529 ammonia Inorganic materials 0.000 claims description 14
GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 13
WUCQGGOGHZRELS-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-amino-2-[2-(4-chlorophenyl)ethoxy]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1OCCC1=CC=C(Cl)C=C1 WUCQGGOGHZRELS-LSCFUAHRSA-N 0.000 claims description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 12
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 claims description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 11
125000003342 alkenyl group Chemical group 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 11
125000003710 aryl alkyl group Chemical group 0.000 claims description 11
150000001412 amines Chemical class 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
239000012414 tert-butyl nitrite Substances 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 9
125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
125000003107 substituted aryl group Chemical group 0.000 claims description 9
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims description 8
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
230000001476 alcoholic effect Effects 0.000 claims description 8
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 8
229910000024 caesium carbonate Inorganic materials 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 8
229940029575 guanosine Drugs 0.000 claims description 8
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 claims description 8
150000007522 mineralic acids Chemical class 0.000 claims description 8
VMOWKUTXPNPTEN-UHFFFAOYSA-N n,n-dimethylpropan-2-amine Chemical compound CC(C)N(C)C VMOWKUTXPNPTEN-UHFFFAOYSA-N 0.000 claims description 8
PPHQUIPUBYPZLD-UHFFFAOYSA-N n-ethyl-n-methylaniline Chemical compound CCN(C)C1=CC=CC=C1 PPHQUIPUBYPZLD-UHFFFAOYSA-N 0.000 claims description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
125000001072 heteroaryl group Chemical group 0.000 claims description 7
GNVRJGIVDSQCOP-UHFFFAOYSA-N n-ethyl-n-methylethanamine Chemical compound CCN(C)CC GNVRJGIVDSQCOP-UHFFFAOYSA-N 0.000 claims description 7
125000000547 substituted alkyl group Chemical group 0.000 claims description 7
239000011734 sodium Substances 0.000 claims description 6
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 6
150000003512 tertiary amines Chemical class 0.000 claims description 6
238000004587 chromatography analysis Methods 0.000 claims description 5
238000006193 diazotization reaction Methods 0.000 claims description 5
238000001704 evaporation Methods 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 5
125000000623 heterocyclic group Chemical group 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
125000004426 substituted alkynyl group Chemical group 0.000 claims description 5
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
YAFMYKFAUNCQPU-UHFFFAOYSA-N 1-(2-bromoethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CCBr)C=C1 YAFMYKFAUNCQPU-UHFFFAOYSA-N 0.000 claims description 4
MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methyl-2-butanol Substances CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims description 4
PKUPAJQAJXVUEK-UHFFFAOYSA-N 2-phenoxyacetyl chloride Chemical compound ClC(=O)COC1=CC=CC=C1 PKUPAJQAJXVUEK-UHFFFAOYSA-N 0.000 claims description 4
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 claims description 4
WMEDSSFYIKNTNG-UHFFFAOYSA-N 3,6-dimethyloctane-3,6-diol Chemical compound CCC(C)(O)CCC(C)(O)CC WMEDSSFYIKNTNG-UHFFFAOYSA-N 0.000 claims description 4
JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 claims description 4
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 4
239000012346 acetyl chloride Substances 0.000 claims description 4
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 4
SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 claims description 4
ASWXNYNXAOQCCD-UHFFFAOYSA-N dichloro(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Cl)(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 ASWXNYNXAOQCCD-UHFFFAOYSA-N 0.000 claims description 4
230000003301 hydrolyzing effect Effects 0.000 claims description 4
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 4
229910052808 lithium carbonate Inorganic materials 0.000 claims description 4
229910017604 nitric acid Inorganic materials 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 4
229960005235 piperonyl butoxide Drugs 0.000 claims description 4
229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
150000003141 primary amines Chemical class 0.000 claims description 4
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 4
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 4
238000000746 purification Methods 0.000 claims description 4
239000011541 reaction mixture Substances 0.000 claims description 4
238000001953 recrystallisation Methods 0.000 claims description 4
150000003335 secondary amines Chemical class 0.000 claims description 4
229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
239000012312 sodium hydride Substances 0.000 claims description 4
229910000104 sodium hydride Inorganic materials 0.000 claims description 4
235000010288 sodium nitrite Nutrition 0.000 claims description 4
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
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 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000001301 oxygen Chemical group 0.000 claims description 3
229910052708 sodium Inorganic materials 0.000 claims description 3
229910052717 sulfur Chemical group 0.000 claims description 3
239000011593 sulfur Chemical group 0.000 claims description 3
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
KMXUKZCMNKLUTF-UHFFFAOYSA-N 1-chloro-4-(2-chloroethyl)benzene Chemical compound ClCCC1=CC=C(Cl)C=C1 KMXUKZCMNKLUTF-UHFFFAOYSA-N 0.000 claims description 2
ZDZQMINKLUECNL-UHFFFAOYSA-N 1-chloro-4-(2-iodoethyl)benzene Chemical compound ClC1=CC=C(CCI)C=C1 ZDZQMINKLUECNL-UHFFFAOYSA-N 0.000 claims description 2
OIWKPVLNEDEDPC-UHFFFAOYSA-N 2-(4-chlorophenyl)ethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCC1=CC=C(Cl)C=C1 OIWKPVLNEDEDPC-UHFFFAOYSA-N 0.000 claims description 2
ANVSTXJFCWYTOM-UHFFFAOYSA-N 2-(4-chlorophenyl)ethyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OCCC1=CC=C(Cl)C=C1 ANVSTXJFCWYTOM-UHFFFAOYSA-N 0.000 claims description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
125000002393 azetidinyl group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
239000011591 potassium Substances 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 description 21
239000000047 product Substances 0.000 description 18
239000007787 solid Substances 0.000 description 17
238000005160 1H NMR spectroscopy Methods 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
125000004432 carbon atom Chemical group C* 0.000 description 11
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
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 8
239000012467 final product Substances 0.000 description 8
229960004592 isopropanol Drugs 0.000 description 7
108050000203 Adenosine receptors Proteins 0.000 description 6
102000009346 Adenosine receptors Human genes 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
230000029936 alkylation Effects 0.000 description 6
238000005804 alkylation reaction Methods 0.000 description 6
230000009615 deamination Effects 0.000 description 6
238000006481 deamination reaction Methods 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
239000000556 agonist Substances 0.000 description 5
125000002947 alkylene group Chemical group 0.000 description 5
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
239000002126 C01EB10 - Adenosine Substances 0.000 description 4
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
229960005305 adenosine Drugs 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
244000309464 bull Species 0.000 description 3
238000001816 cooling Methods 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
239000003446 ligand Substances 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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125000003226 pyrazolyl group Chemical group 0.000 description 1
125000005495 pyridazyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
241000894007 species Species 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
125000005156 substituted alkylene group Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1

Classifications

- 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
- C07H19/16—Purine radicals
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- 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
- C07H19/16—Purine 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
- C07H19/16—Purine radicals
- C07H19/173—Purine radicals with 2-deoxyribosyl as the saccharide radical

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Dermatology (AREA)
Bioinformatics & Cheminformatics (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO20042126A 2001-10-25 2004-05-24 Syntese av 2-aralkoksyadenosiner og 2-alkoksyadenosiner NO326625B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US33516901P	2001-10-25	2001-10-25
US37572302P	2002-04-26	2002-04-26
PCT/US2002/034313 WO2003035662A1 (fr)	2001-10-25	2002-10-24	Synthese d'adenosines 2-aralcoxy et de 2-alcoxyadenosines

Publications (2)

Publication Number	Publication Date
NO20042126L NO20042126L (no)	2004-06-23
NO326625B1 true NO326625B1 (no)	2009-01-19

Family

ID=26989581

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20042126A NO326625B1 (no)	2001-10-25	2004-05-24	Syntese av 2-aralkoksyadenosiner og 2-alkoksyadenosiner
NO20083239A NO20083239L (no)	2001-10-25	2008-07-22	Anvendelse av adenosin A2A reseptor agonist for fremstilling av et topisk medikament for å akselerere helingen av et sår

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20083239A NO20083239L (no)	2001-10-25	2008-07-22	Anvendelse av adenosin A2A reseptor agonist for fremstilling av et topisk medikament for å akselerere helingen av et sår

Country Status (13)

Country	Link
US (1)	US6951932B2 (fr)
EP (1)	EP1446413A4 (fr)
JP (1)	JP2005511551A (fr)
KR (1)	KR20040049001A (fr)
CN (1)	CN1608076A (fr)
AU (1)	AU2002336668B2 (fr)
BR (1)	BR0213557A (fr)
CA (1)	CA2465264C (fr)
IL (2)	IL161608A0 (fr)
NO (2)	NO326625B1 (fr)
NZ (1)	NZ532541A (fr)
PL (1)	PL369327A1 (fr)
WO (1)	WO2003035662A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7342003B2 (en) *	2001-10-25	2008-03-11	King Pharmaceuticals Research And Development, Inc.	Synthesis of 2-aralkyloxyadenosines, 2-alkoxyadenosines, and their analogs
US20070232561A1 (en) *	2006-03-31	2007-10-04	Edward Leung	Pharmaceutical compositions for promoting wound healing
CA2700729A1 (fr)	2007-10-19	2009-04-23	The University Of Tokyo	Agent therapeutique pour le leucoderme et procede d'acceleration de la pigmentation
WO2009085909A1 (fr) *	2007-12-20	2009-07-09	King Pharmaceuticals Research And Development, Inc.	Formes cristallines de 2-[2-(4-chlorophényl)éthoxy]adénosine
JP2020513192A (ja)	2017-03-29	2020-05-07	中国医学科学院基礎医学研究所	低分子ｒｎａ、並びに線維増殖性疾患及び／又は症候群の予防及び／又は治療におけるその応用

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE792155A (fr) *	1971-12-01	1973-05-30	Takeda Chemical Industries Ltd	Nouveaux derives de l'adenosine et leur procede de production
JPS4911896A (fr)	1972-05-15	1974-02-01
JPS4920198A (fr)	1972-06-26	1974-02-22
JPS49124096A (fr)	1973-03-31	1974-11-27
JPS5053393A (fr)	1973-09-18	1975-05-12
US5140015A (en) *	1990-02-20	1992-08-18	Whitby Research, Inc.	2-aralkoxy and 2-alkoxy adenosine derivatives as coronary vasodilators and antihypertensive agents
AU6516494A (en) *	1993-04-15	1994-11-08	New York University	Adenosine receptor agonists for the promotion of wound healing

2002
- 2002-10-24 CA CA2465264A patent/CA2465264C/fr not_active Expired - Fee Related
- 2002-10-24 NZ NZ532541A patent/NZ532541A/en not_active IP Right Cessation
- 2002-10-24 KR KR10-2004-7006198A patent/KR20040049001A/ko not_active Ceased
- 2002-10-24 CN CNA028261437A patent/CN1608076A/zh active Pending
- 2002-10-24 BR BR0213557-4A patent/BR0213557A/pt not_active IP Right Cessation
- 2002-10-24 WO PCT/US2002/034313 patent/WO2003035662A1/fr not_active Ceased
- 2002-10-24 EP EP02773916A patent/EP1446413A4/fr not_active Withdrawn
- 2002-10-24 JP JP2003538175A patent/JP2005511551A/ja active Pending
- 2002-10-24 IL IL16160802A patent/IL161608A0/xx unknown
- 2002-10-24 AU AU2002336668A patent/AU2002336668B2/en not_active Ceased
- 2002-10-24 US US10/281,291 patent/US6951932B2/en not_active Expired - Fee Related
- 2002-10-24 PL PL02369327A patent/PL369327A1/xx not_active Application Discontinuation
2004
- 2004-04-25 IL IL161608A patent/IL161608A/en not_active IP Right Cessation
- 2004-05-24 NO NO20042126A patent/NO326625B1/no not_active IP Right Cessation
2008
- 2008-07-22 NO NO20083239A patent/NO20083239L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
AU2002336668B2 (en)	2008-01-10
US6951932B2 (en)	2005-10-04
NO20083239L (no)	2004-06-23
IL161608A0 (en)	2004-09-27
WO2003035662A1 (fr)	2003-05-01
AU2002336668B8 (en)	2003-05-06
PL369327A1 (en)	2005-04-18
US20030199686A1 (en)	2003-10-23
CA2465264C (fr)	2010-09-07
EP1446413A1 (fr)	2004-08-18
JP2005511551A (ja)	2005-04-28
EP1446413A4 (fr)	2007-10-17
KR20040049001A (ko)	2004-06-10
CN1608076A (zh)	2005-04-20
IL161608A (en)	2010-05-31
BR0213557A (pt)	2004-10-26
NO20042126L (no)	2004-06-23
NZ532541A (en)	2005-09-30
CA2465264A1 (fr)	2003-05-01

Legal Events

Date	Code	Title	Description
2011-05-30	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
AU784374B2 (en)	2006-03-23	Synthesis of 2'-deoxy-L-nucleosides
CA2439879C (fr)	2009-09-15	Nouveaux derives c2,5'disubstitues et n6',c2,5'-trisubstitues de l'adenosine et leurs differentes utilisations
Van Aerschot et al.	1990	Synthesis and anti-HIV evaluation of 2', 3'-dideoxyribo-5-chloropyrimidine analogs: reduced toxicity of 5-chlorinated 2', 3'-dideoxynucleosides
US5869666A (en)	1999-02-09	Conformationally locked nucleoside analogues
CA2465264C (fr)	2010-09-07	Synthese d'adenosines 2-aralcoxy et de 2-alcoxyadenosines
AU2002336668A1 (en)	2003-07-03	Synthesis of 2-aralkoxy adenosines and 2-alkoxyadenosines
US5256650A (en)	1993-10-26	Selective adenosine receptor agents
GB2372741A (en)	2002-09-04	C2,8-Disubstituted adenosine derivatives and their different uses
Hocek et al.	2006	Cytostatic and Antiviral 6-Arylpurine Ribonucleosides VIII. Synthesis and Evaluation of 6-Substituted Purine 3'-Deoxyribonucleosides
US7671191B2 (en)	2010-03-02	Methods for preparing 2-alkynyladenosine derivatives
Marchand et al.	2000	Synthesis and Antiviral Evaluation of Unnatural β-L-Enantiomers of 3′-Fluoro-and 3′-Azido-2, 3′-dideoxyguanosine Derivatives
ITOH et al.	1983	Studies on the Chemical Synthesis of Potential Antimetabolites. XXXIV. Apparent Discrepancy among Reported Proton Nuclear Magnetic Resonance Spectra of 3-Deazaadenosine Is Actually a Reflection of a Difference in Molecular Species
Katayama et al.	2006	Synthesis of Fluorinated Nucleosides
HK1086274A (en)	2006-09-15	Synthesis of 2'-deoxy-l-nucleosides
HK1086275A (en)	2006-09-15	Synthesis of 2'-deoxy-l-nucleosides
EP1600451A2 (fr)	2005-11-30	Synthèse de 2'-déoxy-L-nucléosides
HK1086577A (en)	2006-09-22	Synthesis of 2'-deoxy-l-nucleosides