Compounds, processes and intermediates for synthesis of mixed backbone oligomeric compounds
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07H-019/00
C07H-021/00
출원번호
US-0726096
(2000-11-29)
발명자
/ 주소
Muthiah Manoharan
Martin A. Maier
출원인 / 주소
ISIS Pharmaceuticals, Inc.
대리인 / 주소
Woodcock Washburn LLP
인용정보
피인용 횟수 :
0인용 특허 :
18
초록▼
Synthetic processes are provided wherein mixed backbone oligomeric compounds are prepared having at least one phosphodiester internucleoside linkage in addition to one or more phosphorothioate, phosphoramidate and boranophosphate internucleoside linkages. Novel H-phosphonate intermediates are also d
Synthetic processes are provided wherein mixed backbone oligomeric compounds are prepared having at least one phosphodiester internucleoside linkage in addition to one or more phosphorothioate, phosphoramidate and boranophosphate internucleoside linkages. Novel H-phosphonate intermediates are also disclosed that are useful in the synthetic processes. The synthetic processes use a novel oxidation step to oxidize H-phosphonate internucleoside linkages to phosphodiester internucleoside linkages without degradation of adjacent phosphorothioate, phosphoramidate and boranophosphate internucleoside linkages. Also provided are synthetic intermediates useful in such processes.
대표청구항▼
1. A compound of formula: [EQU9]wherein:T4 is hydroxyl or a protected hydroxyl; Bx is a heterocyclic base moiety; and R2 has one of formula I or II: [EQU10] wherein:E is C1-C10 alkyl, N(R4)(R5) or N.dbd.C(R4)(R5); each R4 and R5 is, independently, H, C1-C10 alkyl, a nitrogen protecting group, or R4
1. A compound of formula: [EQU9]wherein:T4 is hydroxyl or a protected hydroxyl; Bx is a heterocyclic base moiety; and R2 has one of formula I or II: [EQU10] wherein:E is C1-C10 alkyl, N(R4)(R5) or N.dbd.C(R4)(R5); each R4 and R5 is, independently, H, C1-C10 alkyl, a nitrogen protecting group, or R4 and R5, together, are a nitrogen protecting group, or R4 and R5 are joined in a ring structure that can include at least one additional heteroatom selected from a group consisting of nitrogen and oxygen; R3 is OX, SX, or N(X)2; each X is, independently, H, C1-C8 alkyl, C1-C8 haloalkyl, C(.dbd.NH)N(H)Z, C(.dbd.O)N(H)Z or OC(.dbd.O)N(H)Z; Z is H or C1-C8 alkyl; L1, L2 and L3 comprise a ring system having from about 4 to about 7 carbon atoms or having from about 3 to about 6 carbon atoms and at least 1 heteroatom, said heteroatom being selected from a group consisting of oxygen, nitrogen and sulfur, said ring system being aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic; Y is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(R4)(R5)OR4, halo, SR4 or CN; each q1 is, independently, from 2 to 10; each q2 is 0 or 1; p is from 0 to 10; and r is from 1 to 10, provided that when p is 0, r is greater than 1.
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이 특허에 인용된 특허 (18)
Cook Phillip Dan ; Manoharan Muthiah ; Kawasaki Andrew Mamoru, 2'-O-aminooxy-modified oligonucleotides.
Andrus William A. (San Francisco CA) Efcavitch J. William (Belmont CA) McBride Lincoln J. (Redwood City CA), Chemical capping by phosphitylation during oligonucleotide synthesis.
Froehler Brian C. (Belmont CA) Matteucci Mark D. (Redwood City CA), Method of making oligonucleotides, oligonucleoside thiophosphates and oligonucleoside phosphotriesters using H-phosphona.
Cook Phillip Dan ; Sanghvi Yogesh S. ; Sprankle Kelly G. ; Ross Bruce S. ; Griffey Rich H., Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions.
Agrawal Sudhir (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses.
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