US5645985A
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US
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Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
Assignee: Ionis Pharmaceuticals Inc
•
Filing: 1992-11-25
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Granted: 1997-07-08
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Expires: 2012-11-25
Abstract
Abstract Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used used for diagnostic purposes in order to detect viruses or disease conditions.
Inventors
- 👤 Brian Froehler
- 👤 Rick Wagner
- 👤 Mark Matteucci
- 👤 Robert J. Jones
- 👤 Arnold J. Gutierrez
- 👤 Jeff Pudlo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 21:20
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/10; C07H19/16; C07H19/20; C07H21/00; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6813; C12Q1/6839; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
235 words
A nucleomonomer having the structural formula (3) or (4): ##STR11## wherein each X is independently O or S; each R 1 is independently H or a blocking group selected from the group consisting of H-phosphonate, a phosphoramidite, an alkylphosphonamidite, and FMOC; R 2 is selected from the group consisting of vinyl, 1-butenyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1,3-pentadiynyl, 1-propynyl, 1-butynyl, 1-pentynyl, 3-methyl-1-butynyl, 3,3-dimethyl-1-butynyl, 3-buten-1-ynyl, bromovinyl, 1-hexynyl, 1-heptynyl, 1-octynyl, --C.tbd.C--Z wherein Z is C 1-10 alkyl or C 1-10 haloalkyl, 5-heteroaromatic group, and a 5-(1-alkynyl)-heteroaromatic group; wherein the 5-heteroaromatic group and the 5-(1-alkynyl)-heteroaromatic group are optionally substituted on a ring carbon by oxygen or C 1-4 alkyl or substituted on a ring nitrogen by C 1-4 alkyl; Pr is (H) 2 or a protecting group; and R 3 is selected from the group consisting of H, OH, F, OCH 3 , OC 2 H 5 , OC 3 H 7 , SCH 3 , SC 2 H 5 , SC 3 H 7 , OC 3 H 5 , and SC 3 H 5 , with the proviso that if R 3 is H or OH, and both R 1 are H, R 2 is 2-, 3-, and 4-pyridine-ethynyl, 2-pyrimidine-ethynyl, 4-pyrimidine-ethynyl, 5-pyrimidine-ethynyl, triazine-ethynyl, 2-pyrimidinyl, 2- and 4-imidazolyl, 2- and 3-pyrrolyl-ethynyl, 2- and 3-furanyl-ethynyl, 2- and 3-thienyl-ethynyl, 2-, 4- and 5-imidazolyl-ethynyl, 2-, 4-, and 5-thiazolyl-ethynyl, 2-, 4- and 5-oxazolyl-ethynyl, 2-, 4- and 5-thiazolyl, 4- and 5-oxazolyl, or 3-pyrrolyl.
Claim 2
Dependent Claim
235 words
A nucleomonomer having the structural formula (3) or (4): ##STR11## wherein each X is independently O or S; each R 1 is independently H or a blocking group selected from the group consisting of H-phosphonate, a phosphoramidite, an alkylphosphonamidite, and FMOC; R 2 is selected from the group consisting of vinyl, 1-butenyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1,3-pentadiynyl, 1-propynyl, 1-butynyl, 1-pentynyl, 3-methyl-1-butynyl, 3,3-dimethyl-1-butynyl, 3-buten-1-ynyl, bromovinyl, 1-hexynyl, 1-heptynyl, 1-octynyl, --C.tbd.C--Z wherein Z is C 1-10 alkyl or C 1-10 haloalkyl, 5-heteroaromatic group, and a 5-(1-alkynyl)-heteroaromatic group; wherein the 5-heteroaromatic group and the 5-(1-alkynyl)-heteroaromatic group are optionally substituted on a ring carbon by oxygen or C 1-4 alkyl or substituted on a ring nitrogen by C 1-4 alkyl; Pr is (H) 2 or a protecting group; and R 3 is selected from the group consisting of H, OH, F, OCH 3 , OC 2 H 5 , OC 3 H 7 , SCH 3 , SC 2 H 5 , SC 3 H 7 , OC 3 H 5 , and SC 3 H 5 , with the proviso that if R 3 is H or OH, and both R 1 are H, R 2 is 2-, 3-, and 4-pyridine-ethynyl, 2-pyrimidine-ethynyl, 4-pyrimidine-ethynyl, 5-pyrimidine-ethynyl, triazine-ethynyl, 2-pyrimidinyl, 2- and 4-imidazolyl, 2- and 3-pyrrolyl-ethynyl, 2- and 3-furanyl-ethynyl, 2- and 3-thienyl-ethynyl, 2-, 4- and 5-imidazolyl-ethynyl, 2-, 4-, and 5-thiazolyl-ethynyl, 2-, 4- and 5-oxazolyl-ethynyl, 2-, 4- and 5-thiazolyl, 4- and 5-oxazolyl, or 3-pyrrolyl.
Claim 3
Dependent Claim
92 words
The nucleomonomer of claim 1 wherein R 2 is 1-propynyl, 1-propenyl, 3-buten-1-ynyl, 3-methyl-1-butynyl, 3,3-dimethyl-1-butynyl, 1,3-pentadiynyl, 1-butynyl, ethynyl, vinyl, bromovinyl, phenylethynyl, 2-, 3-, and 4-pyridine-ethynyl, 2-, 4- and 5-pyrimidine-ethynyl, triazine-ethynyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-, 4- and 5-oxazolyl-ethynyl, 2-, 4- and 5-thiazolyl-ethynyl, 1-methyl-2-imidazolyl, 2- and 4-imidazolyl, 2-, 4- and 5-oxazolyl, 2-, 4- and 5-imidazolyl-ethynyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2- and 3-thienyl-ethynyl, 2- and 3-furanyl-ethynyl, 2- and 3-pyrrolyl-ethynyl, 2- and 3-thienyl, 2-, 4-, and 5-oxazolyl, 2- and 3-furanyl, or 2- and 3-pyrrolyl; and the blocking group is DMT, MMT, FMOC, hydrogen phosphonate, methylphosphonamidite, methylphosphoramidite or β-cyanoethylphosphoramidite.
Claim 4
Dependent Claim
13 words
The nucleomonomer of claim 2 wherein R 3 is H, OH or O-allyl.
Claim 5
Dependent Claim
10 words
The nucleomonomer of claim 2 wherein R 2 is 1-propynyl.
Claim 6
Dependent Claim
45 words
The nucleomonomer of claim 2 wherein R1 at the 3' position is selected from the group consisting of hydrogen phosphonate, N,N-diisopropylamino-β-cyanoethoxyphosphine, N,N-diisopropyl-aminomethoxyphosphine, N,N-diethylamino-β-cyanoethoxyphosphine, N,N-morpholinomethoxyphosphine, N,N-diisopropylaminomethyl-phosphonamidite, N,N-diethylamino-methylphosphonamidite, bis-morpholino-phosphine, N,N-dimethylamino-β-cyanoethylmercaptophosphine, 2-chlorophenyl phosphate, 4-chlorophenyl phosphate, 2,4-dichlorophenyl phosphate, 2,4-dibromophenyl phosphate, 2-chlorophenyl thiophosphate, 4-chlorophenyl thiophosphate, 2,4-dichlorophenyl thiophosphate and 2,4-thiodibromophenyl phosphate.
Claim 7
Dependent Claim
10 words
The nucleomonomer of claim 1 wherein R 2 is 1-propynyl.
Claim 8
Dependent Claim
51 words
The nucleomonomer of claim 1 wherein X is O; R 1 at the 5' position is DMT, MMT or FMOC; R 1 at the 3' position is N,N-diisopropylamino-β-cyanoethoxyphosphine, N,N-diisopropylaminomethoxy-phosphine or hydrogen phosphonate; R 2 is 1-propynyl, 1-butynyl, 3-methyl-1-butynyl, 2-thienyl, 2-imidazolyl or 2-thiazolyl; and R 3 is H, OH, F, or O-allyl.
Claim 9
Dependent Claim
14 words
The nucleomonomer of claim 7 wherein Pr is benzoyl, diisobutylformamidinyl, FMOC, di-n-butylformamidinyl, or isobutyryl.
Claim 10
Dependent Claim
43 words
The nucleomonomer of claim 1 selected from the group consisting of 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxycytidine, 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-deoxycytidine, 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-deoxycytidine, 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-deoxycytidine, 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxycytidine, 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-methoxycytidine, 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-methoxycytidine, 5-(1 -propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-methoxycytidine, 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-methoxycytidine, and 5-(1-propynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-methoxycytidine.
Claim 11
Dependent Claim
48 words
The nucleomonomer of claim 1 selected from the group consisting of 5-(3-methyl-1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxycytidine, 5-(3-methyl-1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxycytidine, 5-(3-methyl-1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-O-allylcytidine, 5-(3-methyl-1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-O-allylcytidine, 5-(2-thiazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxycytidine, 5-(2-thiazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxycytidine, 5-(2-thiazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-O-allylcytidine, 5-(2-thiazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-O-allylcytidine, 5-(2-imidazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxycytidine, 5-(2-imidazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxycytidine, 5-(2-imidazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-O-allylcytidine, and 5-(2-imidazolyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-O-allylcytidine.
Claim 12
Dependent Claim
42 words
The nucleomonomer of claim 1 selected from the group consisting of 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-deoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-deoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-deoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-methoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-methoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-methoxycytidine, 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-methoxycytidine, and 5-(1-butynyl)-N 4 -diisobutylformamidinyl-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-METHOXYCYTIDINE.
Claim 13
Dependent Claim
38 words
The nucleomoner of claim 1 wherein R 2 is --C.tbd.C--Z wherein Z is H, C 1-10 alkyl or C 1-10 haloalkyl substituted with 1 to 6 halogen atoms selected from the group consisting of flourine, chlorine and bromine.
Claim 14
Dependent Claim
19 words
A nucleomonomer selected from the group consisting of 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-methoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-methoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-methoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-methoxyuridine, and 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-methoxyuridine
Claim 15
Dependent Claim
19 words
A nucleomonomer selected from the group consisting of 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-methoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-methoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-methoxyuridine, 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-methoxyuridine, and 5-(1-propynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-methoxyuridine
Claim 16
Dependent Claim
24 words
A nucleomonomer of claim 1 selected from the group consisting of 5-(3-methyl-1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxyuridine, 5-(3-methyl-1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxyuridine, 5-(3-methyl-1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-O-allyluridine, 5-(3-methyl-1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-O-allyluridine, 5-(2-thiazolyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxyuridine, 5-(2-thiazolyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxyuridine, 5-(2-thiazolyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-O-allyluridine, 5-(2-thiazolyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-O-allyluridine, 5-(2-imidazolyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxyuridine, 5-(2-imidazolyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxyuridine 5-(2-imidazolyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-O-allyluridine, and 5-(2-imidazolyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-O-allyluridine.
Claim 17
Dependent Claim
19 words
A nucleomonomer selected from the group consisting of 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-methoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-methoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-methoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-methoxyuridine, and 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-methoxyuridine.
Claim 18
Dependent Claim
19 words
A nucleomonomer selected from the group consisting of 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-deoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diisopropylphosphoramidite-2'-methoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-dimethylphosphoramidite-2'-methoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N,N-diethylphosphoramidite-2'-methoxyuridine, 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-β-cyanoethyl-N-morpholinophosphoramidite-2'-methoxyuridine, and 5-(1-butynyl)-5'-(4,4'-dimethoxytrityl)-3'-H-phosphonate-2'-methoxyuridine.
Claim 19
Dependent Claim
120 words
A nucleomonomer having the structural formula: ##STR12## wherein each R 1 is independently H or a blocking group; R 2 is --C.tbd.C--Z wherein Z is C 1-10 alkyl or C 1-10 haloalkyl, a 5-(1-alkenyl) group, 5-heteroaromatic group, a 5-(1-alkynyl)-heteroaromatic group optionally substituted on a ring carbon by oxygen or C 1-4 alkyl or substituted on a ring nitrogen by C 1-4 alkyl; Pr is (H) 2 or a protecting group; and R 3 is selected from the group consisting of H, OH, F, OCH 3 , OC 2 H 5 , OC 3 H 7 , SCH 3 , SC 2 H 5 , SC 3 H 7 , OC 3 H 5 , and SC 3 H 5 .
Claim 20
Dependent Claim
120 words
A nucleomonomer having the structural formula: ##STR12## wherein each R 1 is independently H or a blocking group; R 2 is --C.tbd.C--Z wherein Z is C 1-10 alkyl or C 1-10 haloalkyl, a 5-(1-alkenyl) group, 5-heteroaromatic group, a 5-(1-alkynyl)-heteroaromatic group optionally substituted on a ring carbon by oxygen or C 1-4 alkyl or substituted on a ring nitrogen by C 1-4 alkyl; Pr is (H) 2 or a protecting group; and R 3 is selected from the group consisting of H, OH, F, OCH 3 , OC 2 H 5 , OC 3 H 7 , SCH 3 , SC 2 H 5 , SC 3 H 7 , OC 3 H 5 , and SC 3 H 5 .
Claim 21
Dependent Claim
28 words
The compound of claim 16 wherein R 1 is selected from the group consisting of PO 3 -2 , H-phosphonate, a phosphoramidite, an alkylphosphonamidite, DMT, MMT, and FMOC.
Claim 22
Dependent Claim
125 words
A nucleomonomer having the structural formula (3) or (4): ##STR13## wherein each X is independently O or S; each R 1 is independently H or a blocking group; R 2 is --C.tbd.C--Z wherein Z is C 1-10 alkyl, or C 1-10 haloalkyl, a 5(1-alkenyl) group, a 5-heteroaromatic group, a 5-(1-alkynyl)-heteroaromatic group optionally substituted on a ring carbon by oxygen or C 1-4 alkyl or substituted on a ring nitrogen by C 1-4 alkyl; Pr is (H) 2 or a protecting group; and R 3 is selected from the group consisting of OC 2 H 5 , OC 3 H 7 , SCH 3 , SC 2 H 5 , SC 3 H 7 , OC 3 H 5 , and SC 3 H 5 .
Claim 23
Dependent Claim
125 words
A nucleomonomer having the structural formula (3) or (4): ##STR13## wherein each X is independently O or S; each R 1 is independently H or a blocking group; R 2 is --C.tbd.C--Z wherein Z is C 1-10 alkyl, or C 1-10 haloalkyl, a 5(1-alkenyl) group, a 5-heteroaromatic group, a 5-(1-alkynyl)-heteroaromatic group optionally substituted on a ring carbon by oxygen or C 1-4 alkyl or substituted on a ring nitrogen by C 1-4 alkyl; Pr is (H) 2 or a protecting group; and R 3 is selected from the group consisting of OC 2 H 5 , OC 3 H 7 , SCH 3 , SC 2 H 5 , SC 3 H 7 , OC 3 H 5 , and SC 3 H 5 .
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-07-07 | 2001-01-06 | 2001-07-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-07-07 | 2005-01-06 | 2005-07-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-07-07 | 2009-01-06 | 2009-07-08 | $7700.00 | Window Closed / Lapsed |