US5519134A
Expired / Lapsed
US
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Pyrrolidine-containing monomers and oligomers
Assignee: Ionis Pharmaceuticals Inc
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Filing: 1994-01-11
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Granted: 1996-05-21
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Expires: 2014-01-11
Abstract
Abstract Novel pyrrolidine monomers bearing various functional groups are used to prepare oligomeric structures. The pyrrolidine monomers can be joined via standard phosphate linkages including phosphodiester and phosphorothioate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding.
Inventors
- 👤 Oscar L. Acevedo
- 👤 Normand Hebert
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 00:09
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/30; C07D207/32; C07D207/33; C07D207/337; A; A61; A61P; A61P29/00; A61P43/00; C07D207/04; C07D207/10; C07D207/12; C07D231/00; C07D231/02; C07D231/10; C07D231/12; C07D233/00; C07D233/54; C07D233/56; C07D249/00; C07D249/02; C07D249/08; C07D401/00; C07D401/02; C07D401/06; C07D401/14; C07D403/00; C07D403/02; C07D403/06; C07D413/00; C07D413/02; C07D413/06; C07D417/00; C07D417/02; C07D417/12; C07D473/00; C07D473/26; C07D473/32; C07D473/34; C07F; C07F9/00; C07F9/02; C07F9/547; C07F9/553; C07F9/572
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
373 words
A compound having structure I: ##STR3## wherein: X is H, a phosphate group, an activated phosphate group, an activated phosphite group, or a solid support; Y is H or a hydroxyl protecting group; Z is L 1a , L 1b -G 1 , L 2 , L 2 -G 2 , NR 3 R 4 , a nitrogen-containing heterocycle, a phosphate group, a polyether group, a polyethylene glycol group; L 1a is alkyl having 1 to about 20 carbon atoms, alkenyl having 2 to about 20 carbon atoms, or alkynyl having 2 to about 20 carbon atoms; L 1b is alkylene having 1 to about 20 carbon atoms, alkenylene having 2 to about 20 carbon atoms, or alkynylene having 2 to about 20 carbon atoms; L 2 is aryl having 6 to about 14 carbon atoms or aralkyl having 7 to about 15 carbon atoms; G 1 is halogen, OR 1 , SR 2 , NR 3 R 4 , C(═NH)NR 3 R 4 , NHC(═NH)NR 3 R 4 , CH═O, C(═O)OR 5 , CH(NR 3 R 4 )(C(═O)OR 5 ), C(═O)NR 3 R 4 , a metal coordination group, or a phosphate group; G 2 is halogen, OH, SH, SCH 3 , or NR 3 R 4 ; R 1 is H, alkyl having 1 to about 6 carbon atoms, or a hydroxyl protecting group; R 2 is H, alkyl having 1 to about 6 carbon atoms, or a thiol protecting group; R 3 and R 4 are, independently, H, alkyl having 1 to about 6 carbon atoms, or an amine protecting group; R 5 is H, alkyl having 1 to about 6 carbon atoms, or an acid protecting group; Q is L 1b , G 3 , L 1b -G 3 or G 3 -L 1b -G 3 ; G 3 is C(═O), C(═S), C(O)--O, C(O)--NH, C(S)--O, C(S)--NH or S(O) 2 ; n is 0 or 1; wherein if X is H, n is 1, and Q is SO 2 , then Z is not aryl; wherein if n is 0 and Z is L 1a , then X is not H; and wherein if n is 1 and Q is L 1b , then Z is not L 1a .
Claim 2
Dependent Claim
373 words
A compound having structure I: ##STR3## wherein: X is H, a phosphate group, an activated phosphate group, an activated phosphite group, or a solid support; Y is H or a hydroxyl protecting group; Z is L 1a , L 1b -G 1 , L 2 , L 2 -G 2 , NR 3 R 4 , a nitrogen-containing heterocycle, a phosphate group, a polyether group, a polyethylene glycol group; L 1a is alkyl having 1 to about 20 carbon atoms, alkenyl having 2 to about 20 carbon atoms, or alkynyl having 2 to about 20 carbon atoms; L 1b is alkylene having 1 to about 20 carbon atoms, alkenylene having 2 to about 20 carbon atoms, or alkynylene having 2 to about 20 carbon atoms; L 2 is aryl having 6 to about 14 carbon atoms or aralkyl having 7 to about 15 carbon atoms; G 1 is halogen, OR 1 , SR 2 , NR 3 R 4 , C(═NH)NR 3 R 4 , NHC(═NH)NR 3 R 4 , CH═O, C(═O)OR 5 , CH(NR 3 R 4 )(C(═O)OR 5 ), C(═O)NR 3 R 4 , a metal coordination group, or a phosphate group; G 2 is halogen, OH, SH, SCH 3 , or NR 3 R 4 ; R 1 is H, alkyl having 1 to about 6 carbon atoms, or a hydroxyl protecting group; R 2 is H, alkyl having 1 to about 6 carbon atoms, or a thiol protecting group; R 3 and R 4 are, independently, H, alkyl having 1 to about 6 carbon atoms, or an amine protecting group; R 5 is H, alkyl having 1 to about 6 carbon atoms, or an acid protecting group; Q is L 1b , G 3 , L 1b -G 3 or G 3 -L 1b -G 3 ; G 3 is C(═O), C(═S), C(O)--O, C(O)--NH, C(S)--O, C(S)--NH or S(O) 2 ; n is 0 or 1; wherein if X is H, n is 1, and Q is SO 2 , then Z is not aryl; wherein if n is 0 and Z is L 1a , then X is not H; and wherein if n is 1 and Q is L 1b , then Z is not L 1a .
Claim 3
Dependent Claim
12 words
The compound of claim 1 wherein Y is a hydroxyl protecting group.
Claim 4
Dependent Claim
13 words
The compound of claim 2 wherein Y is trityl, methoxytrityl, dimethoxytrityl or trimethoxytrityl.
Claim 5
Dependent Claim
17 words
The compound of claim 1 wherein X is H, an activated phosphite group, or a solid support.
Claim 6
Dependent Claim
10 words
The compound of claim 4 wherein X is a phosphoramidite.
Claim 7
Dependent Claim
17 words
The compound of claim 1 wherein n is 1 and Q is carbonyl, carboxy, acetyl or succinyl.
Claim 8
Dependent Claim
11 words
The compound of claim 1 wherein Z is a nitrogen-containing heterocycle.
Claim 9
Dependent Claim
13 words
The compound of claim 7 wherein said heterocycle is imidazole, pyrrole, or carbazole.
Claim 10
Dependent Claim
9 words
The compound of claim 8 wherein Z is imidazole.
Claim 11
Dependent Claim
13 words
The compound of claim 1 wherein Z is a purine or a pyrimidine.
Claim 12
Dependent Claim
14 words
The compound of claim 10 wherein Z is adenine, guanine, cytosine, uridine, or thymine.
Claim 13
Dependent Claim
9 words
The compound of claim 11 wherein Q is acetyl.
Claim 14
Dependent Claim
16 words
The compound of claim 1 wherein Z is alkyl having 1 to about 20 carbon atoms.
Claim 15
Dependent Claim
138 words
A compound having structure I: ##STR4## wherein: X is H, a phosphate group, an activated phosphate group, an activated phosphite group, or a solid support; Y is H or a hydroxyl protecting group; Z is aryl having 6 to about 14 carbon atoms or aralkyl having 7 to about 15 carbon atoms; L 1b is alkylene having 1 to about 20 carbon atoms, alkenylene having 2 to about 20 carbon atoms, or alkynylene having 2 to about 20 carbon atoms; Q is L 1b , G 3 , L 1b -G 3 or G 3 -L 1b -G 3 ; G 3 is C(═O), C(═S), C(O)--O, C(O)--NH, C(S)--O, C(S)--NH or S(O) 2 ; and n is 0 or 1; wherein if X is H, n is 1, and Q is SO 2 , then Z is not aryl.
Claim 16
Dependent Claim
138 words
A compound having structure I: ##STR4## wherein: X is H, a phosphate group, an activated phosphate group, an activated phosphite group, or a solid support; Y is H or a hydroxyl protecting group; Z is aryl having 6 to about 14 carbon atoms or aralkyl having 7 to about 15 carbon atoms; L 1b is alkylene having 1 to about 20 carbon atoms, alkenylene having 2 to about 20 carbon atoms, or alkynylene having 2 to about 20 carbon atoms; Q is L 1b , G 3 , L 1b -G 3 or G 3 -L 1b -G 3 ; G 3 is C(═O), C(═S), C(O)--O, C(O)--NH, C(S)--O, C(S)--NH or S(O) 2 ; and n is 0 or 1; wherein if X is H, n is 1, and Q is SO 2 , then Z is not aryl.
Claim 17
Dependent Claim
12 words
The compound of claim 14 wherein Z is fluorenylmethyl, phenyl, or benzyl.
Claim 18
Dependent Claim
105 words
A compound having structure I: ##STR5## wherein: X is H, a phosphate group, an activated phosphate group, an activated phosphite group, or a solid support; Y is H or a hydroxyl protecting group; Z is polyethylene glycol or glutamyl; L 1b is alkylene having 1 to about 20 carbon atoms, alkenylene having 2 to about 20 carbon atoms, or alkynylene having 2 to about 20 carbon atoms; Q is L 1b , G 3 , L 1b -G 3 or G 3 -L 1b -G 3 ; G 3 is C(═O), C(═S), C(O)--O, C(O)--NH, C(S)--O, C(S)--NH or S(O) 2 ; n is 0 or 1.
Claim 19
Dependent Claim
105 words
A compound having structure I: ##STR5## wherein: X is H, a phosphate group, an activated phosphate group, an activated phosphite group, or a solid support; Y is H or a hydroxyl protecting group; Z is polyethylene glycol or glutamyl; L 1b is alkylene having 1 to about 20 carbon atoms, alkenylene having 2 to about 20 carbon atoms, or alkynylene having 2 to about 20 carbon atoms; Q is L 1b , G 3 , L 1b -G 3 or G 3 -L 1b -G 3 ; G 3 is C(═O), C(═S), C(O)--O, C(O)--NH, C(S)--O, C(S)--NH or S(O) 2 ; n is 0 or 1.
References Cited (Backward Citations)
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1999-05-21 | 1999-11-20 | 2000-05-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-05-21 | 2003-11-20 | 2004-05-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-05-21 | 2007-11-20 | 2008-05-21 | $7700.00 | Window Closed / Lapsed |