IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0349035
(1999-07-07)
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발명자
/ 주소 |
- Phillip Dan Cook
- Haoyun An
- Tingmin Wang
- Muthiah Manoharan
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출원인 / 주소 |
- ISIS Pharmaceuticals, Inc.
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대리인 / 주소 |
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인용정보 |
피인용 횟수 :
0 인용 특허 :
17 |
초록
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The present invention is directed to nucleoside monomers wherein the 3'-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylenephosphonate linkages. Further, methods of preparing monomers and oligo
The present invention is directed to nucleoside monomers wherein the 3'-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylenephosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.
대표청구항
▼
1. A method of preparing a compound of formula I: [EQU15]wherein:Bx is a protected or unprotected heterocyclic base moiety; T1 is an oligonucleotide, oligonucleoside, nucleoside, nucleotide, H or a hydroxyl protecting group; X1 is O, S or NH; R1 is O, N or S; R2 is H, F, Cl, Br, I, alkyl or substitu
1. A method of preparing a compound of formula I: [EQU15]wherein:Bx is a protected or unprotected heterocyclic base moiety; T1 is an oligonucleotide, oligonucleoside, nucleoside, nucleotide, H or a hydroxyl protecting group; X1 is O, S or NH; R1 is O, N or S; R2 is H, F, Cl, Br, I, alkyl or substituted alkyl; or R1 and R2, together, have one of formulas XI or XII: [EQU16] wherein: Z0 is O, S or NH; E is C1-C alkyl, N(Q3)(Q4) or N.dbd.C(Q3)(Q4); each Q3 and Q4 is, independently, H, C1-C10 alkyl, dialkylaminoalkyl, a nitrogen protecting group, a tethered or untethered conjugate group, a linker to a solid support; or Q3 and Q4, together, form a nitrogen protecting group or a ring structure optionally including at least one additional heteroatom selected from N and O; q1 is an integer from 1 to 10; q2 is an integer from 1 to 10; q3 is 0 or 1; q4 is 0, 1 or 2; each Z1, Z2 and Z3 is, independently, C4-C7 cycloalkyl, C5-C14 aryl or C3-C15 heterocyclyl, wherein the heteroatom in said heterocyclyl group is selected from oxygen, nitrogen and sulfur; Z4 is OM1, SM1, or N(M1)2; each M1 is, independently, H, C1-C8 alkyl, C1-C8 haloalkyl, C(.dbd.NH)N(H)M2, C(.dbd.O)N(H)M2 or OC(.dbd.O)N(H)M2; M2 is H or C1-C8 alkyl; Z5 is C1-C10 alkyl, C1-C10 haloalkyl, C2-C10 alkenyl, C2-C2-C10 alkynyl, C6-C14 aryl, N(Q3)(Q4), OQ3, halo, SQ3 or CN; Z6 is OH, OCH2CH2CN, N(i-Pr)2, dialkylamino, disubstituted alkylamino or O HBy+; a is an integer from 2 to 7; b is 0 or 1; c is 1 or 2; m is 0 or 1; each of Y1 and Y2 is, independently, H, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, cyano, carboxyl, ester or a cyclic moiety; and By is an organic base moiety; comprising the steps of:(a) providing a 5'-protected-3'-substituted alkyl nucleoside of formula III: [EQU17] wherein X is a leaving group; (b) reacting said alkyl nucleoside of formula III with bis(trimethylsilyl)phosphonite in the presence of a base; (c) concentrating the product of step (b); (d) adding methanolic solvent to the product of step (c) to form a solution; and (e) concentrating said solution.
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