CA1339861C - Preparation de 2',3'-dideshydronucleosides - Google Patents

Preparation de 2',3'-dideshydronucleosides

Info

Publication number: CA1339861C
Authority: CA; Canada
Prior art keywords: pyrimidine; dideoxy; formula; purine; base
Prior art date: 1988-03-24
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000616776A

Other languages

English (en)

Inventor

Henry G. Howell

John C. Martin

Carl E. Fuller

John E. Starrett, Jr.

Muzammil M. Mansuri

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

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.)

1988-03-24

Filing date

1993-12-06

Publication date

1998-05-12

1988-03-24 Priority claimed from US07/173,473 external-priority patent/US4904770A/en

1993-12-06 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1998-05-12 Application granted granted Critical

1998-05-12 Publication of CA1339861C publication Critical patent/CA1339861C/fr

2009-03-15 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000000034 method Methods 0.000 claims abstract description 34
239000000543 intermediate Substances 0.000 claims description 26
239000012048 reactive intermediate Substances 0.000 claims description 19
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 17
-1 deaza-purine Chemical compound 0.000 claims description 17
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 15
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
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 12
239000002342 ribonucleoside Substances 0.000 claims description 12
238000003379 elimination reaction Methods 0.000 claims description 11
239000002798 polar solvent Substances 0.000 claims description 11
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 9
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 6
XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical compound N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 claims description 5
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 4
229940045145 uridine Drugs 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000000304 alkynyl group Chemical group 0.000 claims description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 2
125000000262 haloalkenyl group Chemical group 0.000 claims description 2
150000007524 organic acids Chemical class 0.000 claims description 2
DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 claims 1
125000001425 triazolyl group Chemical group 0.000 claims 1
241000725303 Human immunodeficiency virus Species 0.000 abstract description 10
239000003795 chemical substances by application Substances 0.000 abstract description 3
239000003443 antiviral agent Substances 0.000 abstract 1
150000001875 compounds Chemical class 0.000 abstract 1
239000002585 base Substances 0.000 description 43
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
239000000047 product Substances 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
239000007787 solid Substances 0.000 description 17
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
239000002904 solvent Substances 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
239000002777 nucleoside Substances 0.000 description 12
239000003153 chemical reaction reagent Substances 0.000 description 11
239000000203 mixture Substances 0.000 description 10
150000003839 salts Chemical class 0.000 description 10
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
229940113082 thymine Drugs 0.000 description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
235000019439 ethyl acetate Nutrition 0.000 description 6
HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 6
208000030507 AIDS Diseases 0.000 description 5
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
239000006227 byproduct Substances 0.000 description 5
230000000269 nucleophilic effect Effects 0.000 description 5
150000003833 nucleoside derivatives Chemical class 0.000 description 5
AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
150000003230 pyrimidines Chemical class 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000003480 eluent Substances 0.000 description 4
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
150000002905 orthoesters Chemical class 0.000 description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
239000007858 starting material Substances 0.000 description 4
229940104230 thymidine Drugs 0.000 description 4
150000003852 triazoles Chemical group 0.000 description 4
NZXWQUCGACTHLK-POYBYMJQSA-N 1-[(2r,5s)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione Chemical compound C1=C[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 NZXWQUCGACTHLK-POYBYMJQSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical class [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
230000003472 neutralizing effect Effects 0.000 description 3
125000003835 nucleoside group Chemical group 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
238000007142 ring opening reaction Methods 0.000 description 3
239000002002 slurry Substances 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
229940035893 uracil Drugs 0.000 description 3
OOKAXSHFTDPZHP-UHFFFAOYSA-N (1-bromo-2-methyl-1-oxopropan-2-yl) acetate Chemical compound CC(=O)OC(C)(C)C(Br)=O OOKAXSHFTDPZHP-UHFFFAOYSA-N 0.000 description 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
BDZHKUAKSMWSAJ-UHFFFAOYSA-N 2-chloro-n,n-diethyl-1,1,2-trifluoroethanamine Chemical compound CCN(CC)C(F)(F)C(F)Cl BDZHKUAKSMWSAJ-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
JPBRYDQRCOMYRY-IVZWLZJFSA-N [(2r,3s,5r)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-3-methylsulfonyloxyoxolan-2-yl]methyl methanesulfonate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COS(C)(=O)=O)[C@@H](OS(C)(=O)=O)C1 JPBRYDQRCOMYRY-IVZWLZJFSA-N 0.000 description 2
238000005903 acid hydrolysis reaction Methods 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000036436 anti-hiv Effects 0.000 description 2
230000000840 anti-viral effect Effects 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
230000008030 elimination Effects 0.000 description 2
239000012458 free base Substances 0.000 description 2
125000001188 haloalkyl group Chemical group 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
238000000746 purification Methods 0.000 description 2
150000003212 purines Chemical class 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000013341 scale-up Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 2
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
YQHCGMPQZCIQPS-VNSJUHMKSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(trityloxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C(NC(=O)C=C1)=O)O)O)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 YQHCGMPQZCIQPS-VNSJUHMKSA-N 0.000 description 1
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
XDQFBMPFEBUDIC-UHFFFAOYSA-N 1h-pyrimidine-2,4-dione Chemical compound O=C1C=CNC(=O)N1.O=C1C=CNC(=O)N1 XDQFBMPFEBUDIC-UHFFFAOYSA-N 0.000 description 1
WVXRAFOPTSTNLL-NKWVEPMBSA-N 2',3'-dideoxyadenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO)O1 WVXRAFOPTSTNLL-NKWVEPMBSA-N 0.000 description 1
WREGKURFCTUGRC-UHFFFAOYSA-N 4-Amino-1-[5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1C1OC(CO)CC1 WREGKURFCTUGRC-UHFFFAOYSA-N 0.000 description 1
AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
AFBXRHFIVUFPES-UHFFFAOYSA-N 5-methyl-1h-pyrimidine-2,4-dione Chemical group CC1=CNC(=O)NC1=O.CC1=CNC(=O)NC1=O AFBXRHFIVUFPES-UHFFFAOYSA-N 0.000 description 1
UXCAQJAQSWSNPQ-XLPZGREQSA-N Alovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](F)C1 UXCAQJAQSWSNPQ-XLPZGREQSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
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206010020751 Hypersensitivity Diseases 0.000 description 1
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
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AXDLCFOOGCNDST-UHFFFAOYSA-N N-methyl-DL-tyrosine Natural products CNC(C(O)=O)CC1=CC=C(O)C=C1 AXDLCFOOGCNDST-UHFFFAOYSA-N 0.000 description 1
QMCMREXVCYFBIF-HVDHTTBBSA-N Nc1nc2n(cnc2c(=O)[nH]1)[C@@H]1O[C@H](CO)[C@](O)(N=[N+]=[N-])[C@H]1O Chemical compound Nc1nc2n(cnc2c(=O)[nH]1)[C@@H]1O[C@H](CO)[C@](O)(N=[N+]=[N-])[C@H]1O QMCMREXVCYFBIF-HVDHTTBBSA-N 0.000 description 1
208000001388 Opportunistic Infections Diseases 0.000 description 1
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
UMDFLFHAXYPYQN-UKTARXLSSA-N anhydro nucleoside Chemical compound C([C@H]1O[C@H]2N3C=C(C(N=C3O[C@@H]1[C@@H]2F)=O)C)OC(=O)C1=CC=CC=C1 UMDFLFHAXYPYQN-UKTARXLSSA-N 0.000 description 1
239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
229940124411 anti-hiv antiviral agent Drugs 0.000 description 1
230000001399 anti-metabolic effect Effects 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
239000003124 biologic agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
229940045348 brown mixture Drugs 0.000 description 1
238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000007541 cellular toxicity Effects 0.000 description 1
239000013043 chemical agent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
229940104302 cytosine Drugs 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000006642 detritylation reaction Methods 0.000 description 1
RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
229960005102 foscarnet Drugs 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
239000000411 inducer Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000003760 magnetic stirring Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000003328 mesylation reaction Methods 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
238000005935 nucleophilic addition reaction Methods 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000002245 particle Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
239000002212 purine nucleoside Substances 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
239000002718 pyrimidine nucleoside Substances 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
229960000329 ribavirin Drugs 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
239000000126 substance Substances 0.000 description 1
FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
229960005314 suramin Drugs 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
238000005866 tritylation reaction Methods 0.000 description 1
230000010415 tropism Effects 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
239000003643 water by type Substances 0.000 description 1

Landscapes

Saccharide Compounds (AREA)

CA000616776A 1988-03-24 1993-12-06 Preparation de 2',3'-dideshydronucleosides Expired - Fee Related CA1339861C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US07/173,473 US4904770A (en)	1988-03-24	1988-03-24	Production of 2',3'-dideoxy-2',3'-didehydronucleosides
US173,473		1988-03-24
CA000593738A CA1339448C (fr)	1988-03-24	1989-03-15	Obtention de 2',3'-didesoxy-2',3-dideshydronucleosides

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000593738A Division CA1339448C (fr)	1988-03-24	1989-03-15	Obtention de 2',3'-didesoxy-2',3-dideshydronucleosides

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000617047A Division CA1339483C (fr)	1988-03-24	1996-03-21	Preparation de 2',3'-didesoxy-2',3-dideshydro-nucleosides

Publications (1)

Publication Number	Publication Date
CA1339861C true CA1339861C (fr)	1998-05-12

Family

ID=25672525

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA000616776A Expired - Fee Related CA1339861C (fr)	1988-03-24	1993-12-06	Preparation de 2',3'-dideshydronucleosides
CA000617047A Expired - Fee Related CA1339483C (fr)	1988-03-24	1996-03-21	Preparation de 2',3'-didesoxy-2',3-dideshydro-nucleosides

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA000617047A Expired - Fee Related CA1339483C (fr)	1988-03-24	1996-03-21	Preparation de 2',3'-didesoxy-2',3-dideshydro-nucleosides

Country Status (1)

Country	Link
CA (2)	CA1339861C (fr)

1993
- 1993-12-06 CA CA000616776A patent/CA1339861C/fr not_active Expired - Fee Related
1996
- 1996-03-21 CA CA000617047A patent/CA1339483C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA1339483C (fr)	1997-09-30

Legal Events

Date	Code	Title	Description
2001-05-14	MKLA	Lapsed

Publication	Publication Date	Title
CA1339448C (fr)	1997-09-09	Obtention de 2',3'-didesoxy-2',3-dideshydronucleosides
Herdewijn et al.	1987	3'-Substituted 2', 3'-dideoxynucleoside analogs as potential anti-HIV (HTLV-III/LAV) agents
WO1989012061A1 (fr)	1989-12-14	Nucleosides de pyrimidine et intermediaires
US4908440A (en)	1990-03-13	2',3'-dideoxy-2'-fluoroarabinopyrimidine nucleosides
US5128458A (en)	1992-07-07	2',3'-dideoxy-4'-thioribonucleosides as antiviral agents
JPH04507086A (ja)	1992-12-10	ヌクレオシド誘導体および医薬としてのそれらの使用
US5130421A (en)	1992-07-14	Production of 2',3'-dideoxy-2',3'-didehydronucleosides
FI95384C (fi)	1996-01-25	Menetelmä 3'-deoksi-3'-substituoitujen metyylinukleosidien valmistamiseksi ja menetelmässä käytettäviä välituotteita
Kasnar et al.	1994	Synthesis of 2′, 3′-Dideoxy-and 3′-Azido-2′, 3′-dideoxy-pyridazine Nucleosides as Potential Antiviral Agents
WO1994014831A1 (fr)	1994-07-07	Nucleosides de dihydropyrimidine a proprietes antivirales
CZ21996A3 (en)	1996-05-15	Oxathiolates, process of their preparation and pharmaceutical compositions containing thereof
CA1339483C (fr)	1997-09-30	Preparation de 2',3'-didesoxy-2',3-dideshydro-nucleosides
EP0340778A2 (fr)	1989-11-08	Prodrogues de 2',3'-didéshydro-2',3'-didésoxynucléosides
US5212294A (en)	1993-05-18	Production of 2',3'-dideoxy-2',3'-didehydronucleosides
NZ238678A (en)	1991-12-23	Process for preparing 2',3'-dideoxy-2',3'-didehydronucleosides
KR0142110B1 (ko)	1998-07-01	2', 3'-디데옥시-2', 3'-디데히드로누클레오시드의 제조방법
US5478928A (en)	1995-12-26	2',3'-dideoxy-4'-thioribonucleosides and synthetic precursors thereof
IL105571A (en)	1994-05-30	Production of 2'-3'-dideoxy-2'3'- didehydronucleosides
NO171314B (no)	1992-11-16	Fremgangsmaate for fremstilling av 2',3'-dideoksy-2',3'-didehydronukleosider
NO171315B (no)	1992-11-16	Fremgangsmaate for fremstilling av 2',3'-dideoksy-2',3'-didehydronukleosider
NO171316B (no)	1992-11-16	Fremgangsmaate for fremstilling av 2',3'-dideoksy-2',3'-didehydronukleosider r
US5506215A (en)	1996-04-09	1-(3'-fluoro-2',3'-dideoxy-β-D-ribofuranosyl)-5-substituted pyrimidine nucleosides
Faraj et al.	1992	Synthesis and evaluation of new 2′, 3′-dideoxynucleoside analogs as potential anti-AIDS and anti-herpes drugs
NO172345B (no)	1993-03-29	Fremgangsmaate for fremstilling av 2',3'-dideoksy-2',3'-didehydronukleosider
KR920004982B1 (ko)	1992-06-22	2',3'-디데옥시-2',3'-디데히드로-2'-플루오로뉴클레오사이드류