Patent US5212295A successfully refreshed from Google Patents.
US5212295A
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Monomers for preparation of oligonucleotides having chiral phosphorus linkages
Assignee: Ionis Pharmaceuticals Inc
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Filing: 1991-10-15
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Granted: 1993-05-18
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Expires: 2011-10-15
Abstract
Abstract Sequence-specific oligonucleotides are provided having substantially pure chiral Sp phosphorothioate, chiral Rp phosphorothioate, chiral Sp alkylphosphonate, chiral Rp alkylphosphonate, chiral Sp phosphoamidate, chiral Rp phosphoamidate, chiral Sp phosphotriester, and chiral Rp phosphotriester linkages. The novel oligonucleotides are prepared via a stereospecific SN 2 nucleophilic attack of a phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate anion on the 3' position of a xylonucleotide. The reaction proceeds via inversion at the 3' position of the xylo reactant species, resulting in the incorporation of phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate linked ribofuranosyl sugar moieties into the oligonucleotide.
Inventors
- 👤 Phillip D. Cook
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 20:58
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/10; C07H19/16; C07H19/20; C07H21/00; C07H23/00; C07J; C07J43/00; C07J43/003; C12; C12N; C12N15/00; C12N15/09; C12N15/10; C12N15/11; C12N15/113; C12N15/1137; C12N9/00; C12N9/0004; C12N9/0069; C12P; C12P19/00; C12P19/26; C12P19/28; C12P19/30; C12P19/34; C12Q; C12Q1/00; C12Q1/68; C12Q1/6813; C12Q1/6876; C12Q1/70; C12Q1/701; C12Y; C12Y113/00; C12Y113/11; C12Y113/11012; A61K38/00; A61K48/00; C12N2310/00; C12N2310/30; C12N2310/31; C12N2310/312; C12N2310/3125; C12N2310/315; C12N2310/32; C12N2310/321; C12N2310/322; C12N2310/33; C12N2310/333; C12N2310/336; C12N2310/35; C12N2310/352; C12N2310/3521; C12N2310/3523; C12N2310/3527; C12N2310/353; C12N2310/3531; C12N2310/3533
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
186 words
A compound having the structure: ##STR10## wherein: Q is O or CH 2 ; R D is O, S, methyl, O--C 1 -C 12 -alkyl, S--C 1 -C 12 -alkyl, amino or substituted amino, where said substituent is C 1 -C 12 -alkyl or C 6 -C 14 -aryl; R E is O or S; R F is H or a blocking group; R X is H, OH, C 1 -C 12 -alkyl, substituted C 1 -C 12 -alkyl, F, Cl, Br, OCF 3 , O--C 1 -C 12 -alkyl, O-substituted C 1 -C 12 -alkyl, OCH 2 CH═CH 2 , OCH 2 CCH, and C(O)--C 1 -C 12 -alkyl, wherein said substituent is C 1 -C 12 -haloalkyl, C 1 -C 12 -alkenyl, C 1 -C 12 -alkoxy, C 1 -C 12 -thioalkoxy, C 1 -C 12 -haloalkoxy, C 6 -C 14 -aryl, halogen, hydroxyl, amino, azido, carboxy, cyano, nitro, or mercapto; B X is a nucleoside base or a blocked nucleoside base; and L is a leaving group or together L and Bx are a C2 or C6 pyrimidine-3'xylo cyclo-nucleoside or C8 purine-3'xylo cyclo-nucleoside.
Claim 2
Dependent Claim
186 words
A compound having the structure: ##STR10## wherein: Q is O or CH 2 ; R D is O, S, methyl, O--C 1 -C 12 -alkyl, S--C 1 -C 12 -alkyl, amino or substituted amino, where said substituent is C 1 -C 12 -alkyl or C 6 -C 14 -aryl; R E is O or S; R F is H or a blocking group; R X is H, OH, C 1 -C 12 -alkyl, substituted C 1 -C 12 -alkyl, F, Cl, Br, OCF 3 , O--C 1 -C 12 -alkyl, O-substituted C 1 -C 12 -alkyl, OCH 2 CH═CH 2 , OCH 2 CCH, and C(O)--C 1 -C 12 -alkyl, wherein said substituent is C 1 -C 12 -haloalkyl, C 1 -C 12 -alkenyl, C 1 -C 12 -alkoxy, C 1 -C 12 -thioalkoxy, C 1 -C 12 -haloalkoxy, C 6 -C 14 -aryl, halogen, hydroxyl, amino, azido, carboxy, cyano, nitro, or mercapto; B X is a nucleoside base or a blocked nucleoside base; and L is a leaving group or together L and Bx are a C2 or C6 pyrimidine-3'xylo cyclo-nucleoside or C8 purine-3'xylo cyclo-nucleoside.
Claim 3
Dependent Claim
56 words
The compound of claim 1 wherein L is selected from the group consisting of halogen, C 1 -C 12 -alkyl-sulfonyl, substituted C 1 -C 12 -alkylsulfonyl, C 6 -C 14 -arylsulfonyl, substituted C 6 -C 14 -arylsulfonyl, trichloroacetimidate, and C(O)-C 1 -C 12 -alkyl, wherein said substituent is halogen, hydroxyl, amino, azido, carboxy, cyano, or nitro.
Claim 4
Dependent Claim
32 words
The compound of claim 1 wherein L is selected from the group consisting of chloro, fluoro, bromo, iodo, p-(2,4-dinitroanilino)benzenesulfonyl, benzenesulfonyl, methylsulfonyl (mesylate), p-methylbenzenesulfonyl (tosylate), p-bromobenzenesulfonyl, trifluoromethylsulfonyl (triflate), trichloroacetimidate, 2,2,2-trifluoroethanesulfonyl, imidazolesulfonyl and 2,4,6-trichlorophenyl.
Claim 5
Dependent Claim
20 words
The compound of claim 1 wherein R F is selected from the group consisting of H, t-butyl, dimethoxytrityl or tetrahydropyranyl.
Claim 6
Dependent Claim
14 words
The compound of claim 1 wherein B X is a pyrimidinyl-1 or purinyl-9 moiety.
Claim 7
Dependent Claim
18 words
The compound of claim 1 wherein B X is adenine, guanine, hypoxanthine, uracil, thymine, cytosine, 2-aminoadenine or 5-methylcytosine.
Claim 8
Dependent Claim
9 words
The compound of claim 1 wherein Q is O.
Claim 9
Dependent Claim
8 words
The compound of claim 1 having Sp stereochemistry.
Claim 10
Dependent Claim
8 words
The compound of claim 1 having Rp stereochemistry.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1996-05-17 | 1996-11-16 | 1997-05-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2000-05-17 | 2000-11-16 | 2001-05-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2004-05-17 | 2004-11-16 | 2005-05-18 | $7700.00 | Window Closed / Lapsed |