Pyrimidine derivatives for labeled binding partners
First Claim
Patent Images
1. A compound having the structure (1):
-
and tautomers, solvates and salts thereof, whereinR1 is —
H or a binding partner having the structure 2, 2(A), 2(B), or 2(C);
whereinD is —
OH, protected —
OH, an oligonucleotide coupling group or a solid support;
D1 is an oligonucleotide coupling group, —
OH, protected —
OH or a solid support, wherein D1 is bonded to one 2′
or 3′
position in the oligonucleotide of structure (2) and the adjacent 2′
or 3′
position in structure (2) is substituted with R21, provided that D and D1 are not both an oligonucleotide coupling group or they are not both a solid support;
D2 is —
CO2R5, —
C(O)N(R5)2, —
SO3R5, —
SO2N(R5)2 or an activated derivative of —
CO2H or —
SO3H;
D3 is a protecting group, —
H or —
(CH2)2-6—
N(R5)2, R4 independently a phosphodiester linkage or a phosphodiester substitute linkage, wherein R4 is bonded to one 2′
or 3′
position in the structure (2) oligonucleotide and the adjacent 2′
or 3′
position in structure (2) substituted with R21;
R5 is independently —
H or a protecting group;
R21 is independently —
H, —
OH, halogen or a moiety that enhances the oligonucleotide against nuclease cleavage;
R37 is independently —
O—
, —
CH2—
or —
CF2—
;
n is an integer from 0 to 98; and
B independently is a purine or pyrimidine base or a protected derivative thereof, provided that at least one B is a base of structure (3) R2 is A(Z)X1, wherein A is a spacer and Z independently is a label bonding group optionally bonded to a detectable label, but R2 is not amine, protected amine, nitro or cyano;
R27 is independently —
CH═
, —
N═
, —
C(C1-C8 alkyl)═
or —
C(halogen)═
, but no adjacent R27 are both —
N═
, or two adjacent R27 are taken together to form a ring having the structure,
where Ra is independently —
CH═
, —
N═
, —
C(C1-C8 alkyl)═
or —
C(halogen)═
, but no adjacent Ra are both —
N═
;
R34 is —
O—
, —
S—
or —
N(CH3)—
;
R40 independently is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, a protecting group or both R40 together with the nitrogen atom to which they are attached form;
and X1 is 1, 2 or 3.
2 Assignments
0 Petitions
Accused Products
Abstract
Compounds having structure (1)
wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.
-
Citations
41 Claims
-
1. A compound having the structure (1):
-
and tautomers, solvates and salts thereof, wherein R1 is —
H or a binding partner having the structure 2, 2(A), 2(B), or 2(C);
wherein D is —
OH, protected —
OH, an oligonucleotide coupling group or a solid support;
D1 is an oligonucleotide coupling group, —
OH, protected —
OH or a solid support, wherein D1 is bonded to one 2′
or 3′
position in the oligonucleotide of structure (2) and the adjacent 2′
or 3′
position in structure (2) is substituted with R21, provided that D and D1 are not both an oligonucleotide coupling group or they are not both a solid support;
D2 is —
CO2R5, —
C(O)N(R5)2, —
SO3R5, —
SO2N(R5)2 or an activated derivative of —
CO2H or —
SO3H;
D3 is a protecting group, —
H or —
(CH2)2-6—
N(R5)2,R4 independently a phosphodiester linkage or a phosphodiester substitute linkage, wherein R4 is bonded to one 2′
or 3′
position in the structure (2) oligonucleotide and the adjacent 2′
or 3′
position in structure (2) substituted with R21;
R5 is independently —
H or a protecting group;
R21 is independently —
H, —
OH, halogen or a moiety that enhances the oligonucleotide against nuclease cleavage;
R37 is independently —
O—
, —
CH2—
or —
CF2—
;
n is an integer from 0 to 98; and
B independently is a purine or pyrimidine base or a protected derivative thereof, provided that at least one B is a base of structure (3) R2 is A(Z)X1, wherein A is a spacer and Z independently is a label bonding group optionally bonded to a detectable label, but R2 is not amine, protected amine, nitro or cyano;
R27 is independently —
CH═
, —
N═
, —
C(C1-C8 alkyl)═
or —
C(halogen)═
, but no adjacent R27 are both —
N═
, or two adjacent R27 are taken together to form a ring having the structure,
where Ra is independently —
CH═
, —
N═
, —
C(C1-C8 alkyl)═
or —
C(halogen)═
, but no adjacent Ra are both —
N═
;
R34 is —
O—
, —
S—
or —
N(CH3)—
;
R40 independently is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, a protecting group or both R40 together with the nitrogen atom to which they are attached form;
and X1 is 1, 2 or 3. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23)
R3 is independently —
H, —
CH3, —
CH2CH3, CH2)w—
N(R33)2 or a protecting group, or both R3 together are a protecting group, or when R2 is —
R6—
(CH2)t—
N(R3)2, one R3 is —
H, —
CH3, —
CH2CH3, a protecting group or —
(CH2)w—
N(R33)2 and the other R3 is —
H, —
CH3, —
CH2CH3, —
(CH2)w—
N(R33)2, —
CH(N[R33]2)—
N(R33)2,R5 is independently H or a protecting group;
R6 is independently —
S, —
NR5—
, —
O—
or —
CH2—
;
R7 is independently linear alkyl having 1, 2, 3 or 4 carbon atoms optionally substituted with one —
CH═
CH—
, —
C≡
C—
or —
CH2—
O—
CH2—
moiety, or R7 is cyclic alkyl having 3, 4 or 5 carbon atoms, wherein one of the linear alkyl carbon atoms is optionally substituted with a single —
CH3, —
CN, ═
O, —
OH or protected hydroxyl, provided that the carbon atoms in any —
CH═
CH—
or —
CH2—
O—
CH2—
moiety are not substituted with ═
O, —
OH or protected hydroxyl;
R8 is linear alkylene having 1 or 2 carbon atoms wherein one alkylene carbon atom is optionally substituted with a single —
CH3, —
CN, ═
O, —
OH or protected hydroxyl, or R8 is absent;
R28 is independently —
CH2—
, —
CH(CH3)—
, —
CH(OCH3)—
, —
CH(OR5)—
or —
O—
, but both are not —
O—
;
R29 is independently —
N—
, —
N(CH3)—
, —
CH—
, —
C(CH3)—
, but both are not —
N(CH3)—
;
R30 is —
H or —
N(R3)2;
R31 is the side chain of an amino acid;
R33 is independently —
H, —
CH3, —
CH2CH3 or a protecting group;
R35 is H, C1-C4 alkyl or a protecting group;
R36 is —
H, —
CH3, —
CH2CH3, a protecting group or an optionally protected monosaccharide;
t is 1, 2, 3 or 4, but when R6 is —
O—
, —
S—
or —
NR5—
, t is 2, 3 or 4;
v is independently 0, 1 or 2; and
w is independently 1 or 2.
-
-
4. The compound of claim 3 wherein R2 is —
- CH2—
(CH2)tN(R3)2, —
NR5—
(CH2)tN(R3)2, —
S—
(CH2)tN(R3)2, —
O—
(CH2)tN(R3)2, —
O—
(CH2)tNR5C(NR5)(NR3)2, —
(CH2)1-2—
O—
(CH2)tN(R3)2, —
R6—
CH2—
CHR31—
N(R3)2, —
R6—
(R7)v—
N(R3)2, —
R6—
(CH2)t—
NR5C(NR5)(NR3)2, or —
CH2(CH2)tNR5C(NR5)(NR3)2.
- CH2—
-
5. The compound of claim 4 wherein t is 2.
-
6. The compound of claim 5 wherein R3 independently is —
- H, —
CH3—
C2H5 or a protecting group.
- H, —
-
7. The compound of claim 6 wherein R2 is —
- O—
(CH2)2—
NH2, —
O—
(CH2)3—
NH2, —
O—
(CH2)2—
N(CH3)2, —
O—
(CH2)3—
N(CH3)2, —
O—
(CH2)2—
NHCH3, —
O—
(CH2)3—
NHCH3, —
O—
CH2—
CH(CH3)—
NH2, —
CH2—
O—
(CH2)2—
NH2, —
CH2—
O—
(CH2)3—
NH2 or —
(CH2)2—
O—
(CH2)2—
NH2.
- O—
-
8. The compound of claim 3 wherein t is 2 or 3.
-
9. The compound of claim 1 wherein R4 is independently 3′
- -O—
P(S)(S)—
O-5′
, 3′
-O—
P(S)(O)—
O-5′
, 3′
-O—
P(O)(O)—
O-5′
, 3′
-O—
P(Me)(O)—
O-5′
, 3′
-NH—
P(O)(O)—
O-5′
, 2′
-S—
CH2—
O-5′
, 3′
-O—
CH2—
O-5′
, 2′
-O—
CH2—
O-5′
, 3′
-O—
P(Me)(S)—
O-5′
, 3′
-CH2—
N(CH3)—
O-5′
, or 3′
-R38—
P(N(R40)2)(O)—
O-5′
, whereinR38 independently is —
O—
, —
CH2—
, or —
NH—
.
- -O—
-
10. The compound of claim 1, wherein R2 is —
- R6—
(CH2)tNR5CNR5N(R3)2, —
R6CH2—
CHR31—
N(R3)2, —
R6—
(R7)v—
N(R3)2, —
R6—
(CH2)t—
N(R3)2, —
O—
(CH2)1-2—
O—
(CH2)t—
N(R3)2,R3 is independently —
H, —
CH3, —
CH2CH3, —
O—
(CH2)w—
N(R3)2 or a protecting group, or both R3 together are a protecting group, or when R2 is —
R6—
(CH2)t—
N(R33)2, one R3 is —
H, —
CH3, —
CH2CH3, a protecting group or —
(CH2)w—
N(R33)2 and the other R3 is —
H, —
CH3, —
CH2CH3, —
(CH2)w—
N(R33)2, —
CH(N(R33)2)—
N(R33)2,R5 is independently H or a protecting group;
R6 is independently —
S—
, —
NR5—
, —
O—
or —
CH2—
;
R7 is independently linear alkyl having 1, 2, 3 or 4 carbon atoms optionally substituted with one —
CH═
CH—
, —
C═
C—
or —
CH2—
O—
CH2—
moiety, or R7 is cyclic alkyl having 3, 4 or 5 carbon atoms, wherein one of the linear alkyl carbon atoms is optionally substituted with a single —
CH3, —
CN, ═
O, —
OH or protected hydroxyl, provided that the carbon atoms in any —
CH═
CH—
or —
CH2—
O—
CH2—
moiety are not substituted with ═
O, —
OH or protected hydroxyl;
R8 is linear alkylene having 1 or 2 carbon atoms wherein one alkylene carbon atom is optionally substituted with a single —
CH3, —
CN, ═
O, —
OH or protected hydroxyl, or R8 is absent;
R28 is independently —
CH2—
, —
CH(CH3)—
, —
CH(OCH3)—
, —
CH(OR5)—
or —
O—
, but both are not —
O—
;
R29 is independently —
N—
, —
N(CH3)—
, —
CH—
, —
C(CH3)—
, but both are not —
N(CH3)—
;
R30 is —
H or —
N(R3)2;
R31 is the side chain of an amino acid;
R33 is independently —
H, —
CH3, —
CH2CH3 or a protecting group;
R35 is H, C1-C4 alkyl or a protecting group;
R36 is H, —
CH3, —
CH2CH3, a protecting group or an optionally protected monosaccharide;
t is 1, 2, 3 or 4, but when R6 is —
O—
, —
S—
or —
NR5—
, t is 2, 3 or 4;
v is independently 0, 1 or 2; and
w is independently 1 or 2.
- R6—
-
11. The compound of claim 10 wherein R2 is —
- CH2—
(CH2)tN(R3)2, —
NR5—
(CH2)tN(R3)2, —
S—
(CH2)tN(R3)2, —
O—
(CH2)tN(R3)2, —
O—
(CH2)tNR5C(NR5)(NR3)2, —
O—
(CH2)1-2—
O—
(CH2)tN(R3)2, —
R6—
CH2—
CHR31—
N(R3)2, —
R6—
(R7)v—
N(R3)2, —
R6—
(CH2)tNR5C(NR5)(NR3)2, or —
CH2(CH2)tNR5C(NR5)(NR3)2.
- CH2—
-
12. The compound of claim 11 therein t is 2 or 3.
-
13. The compound of claim 12 wherein R3 independently is —
- H, —
CH3, —
C2H5 or a protecting group.
- H, —
-
14. The compound of claim 13 wherein R2 is —
- O—
(CH2)2—
NH2, —
O—
(CH2)3—
NH2, —
O—
(CH2)2—
N(CH3)2, —
O—
(CH2)3—
N(CH3)2, —
O—
(CH2)2—
NHCH3, —
O—
(CH2)3—
NHCH3, —
O—
CH2—
CH(CH3)—
NH2, —
CH2—
O—
(CH2)2—
NH2, —
CH2—
O—
(CH2)3—
NH2 or —
(CH2)2—
O—
(CH2)2—
NH2.
- O—
-
15. The compound of claim 1 wherein R21 is independently —
- H, —
OH, halogen, protected hydroxyl, —
O-methyl, O-ethyl, O-n-propyl, O-allyl, —
O—
(CH2)2—
OH, —
O—
(CH2)3—
OH, —
O—
(CH2)2—
F, —
O—
(CH2)s—
F, —
O—
(CH2)s—
R65, —
O—
(CH2)2—
(O—
(CH2)2)r—
R65, —
O—
(CH2)r—
O—
(CH2)r—
O—
(CH2)rR65, —
NH-methyl, —
NH-ethyl, —
NH-n-propyl, —
NH—
(CH2)2OH, —
NH—
(CH2)3OH, —
NH—
(CH2)s—
R65, —
S-methyl, —
S-ethyl, —
S-n-propyl, —
S-allyl, —
S—
(CH2)2—
OH, —
S—
(CH2)3—
OH, —
S—
(CH2)2—
F, —
S—
(CH2)s—
R65, or —
S—
(CH2)2—
(O—
(CH2)2)r—
R65, wherein;R65 is —
H, —
F, —
OH, —
OCH3, —
NH2, —
SH, protected hydroxyl, protected amino or protected thiol;
r is 1, 2, 3, or 4; and
s is 2, 3, 4, 5, 6, 7 or 8.
- H, —
-
16. A compound according to claim 1, having a structure selected from the group consisting of:
-
wherein R1 is a binding partner, a protecting group, a linker or H.
-
-
17. The compound of claim 15 wherein R21 is independently —
- H, —
OH, —
F, protected hydroxyl, —
OCH3, —
O—
CH2CH3, —
O—
CH2CH2OH, —
O—
CH2CH2F, —
O—
CH2CH2CH3, —
O—
CH2CH2CH2OH, —
O—
CH2CH2CH2F, —
O—
CH2CF2H, —
O—
CH2CF3 or —
O—
CH2CH2—
O—
CH3.
- H, —
-
18. The compound of claim 1 wherein B independently are selected from the group consisting of a base of structure (3), guanosine, adenine, thymine, uracil, cytosine, 5-methylcytosine, 5-(1-propynyl)uracil, 5-(1-propynly)cytosine, 5-(1-butynyl)uracil or 5-(1-butynyl)cytosine.
-
19. The compound of claim 1 wherein D1 is H-phosphonate, a methylphosphonamidite, a β
- -cyanoethylphosphoramidite or a phosphoramidite.
-
20. A compound having the structure (4):
-
and tautomers, solvates and salts thereof, wherein R1, R2 and R27 have the meanings given in claim 1;
R24 is hydrogen;
R25 is —
SH, —
OH, ═
S or ═
O.
-
-
21. The compound of claim 20 where R1 is —
- H or optionally protected monosaccharide.
-
22. The compound of claim 21 wherein the optionally protected monosaccharide is 2′
- -deoxy-R21-substituted ribose.
-
23. The compound of claim 22 wherein R21 is —
- H, —
OH, —
F, protected hydroxyl, —
OCH3, —
O—
CH2CH3, —
O—
CH2CH2OH, —
O—
CH2CH2F, —
O—
CH2CH2CH3, —
O—
CH2CH2CH2OH, —
O—
CH2CH2CH2F, —
O—
CH2CF2H, —
O—
CH2CF3or —
O—
CH2CH2—
O—
CH3.
- H, —
-
24. A compound having the structure (1):
-
or tautomers, solvates or salts thereof, wherein; R1 is an oligonucleotide, a protecting group, a linker or —
H;
R2 is —
R6—
(CH2)tNR5C(NR5)N(R3)2;
R3 is independently —
H, —
CH3, —
CH2CH3, —
(CH2)w—
N(R33)2 or a protecting group, or both R3 together are a protecting group;
R5 independently H or a protecting group;
R6 is independently —
S—
, —
NR5—
, —
O—
, —
CH2—
;
R33 is independently —
H, —
CH3, —
CH2CH3 or a protecting group;
each R27 is, independently —
CH═
, —
N═
, —
C(C1-C8 alkyl)═
or —
C(halogen)═
, with the proviso that no two adjacent groups R27 are both —
N═
;
alternatively, adjacent R27 are taken together to form a ring having the structure;
wherein each Ra is, independently —
CH═
, —
N═
, —
C(C1-8 alkyl)═
or —
C(halogen)═
, with the proviso that no two adjacent groups Ra are both —
N═
;
R34 is —
O—
, —
S—
or —
N(CH3)—
;
w is independently 1 or 2; and
t is 1, 2, 3, or 4. - View Dependent Claims (25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 41)
wherein; D is —
OH, protected —
OH, an oligonucleotide coupling group or a solid support;
D1 is an oligonucleotide coupling group, —
OH, protected —
OH or a solid support, wherein D1 is bonded to one 2′
or 3′
position in the oligonucleotide of structure (2) and the adjacent 2′
or 3′
position in structure (2) is substituted with R21, provided that D and D1 are not both an oligonucleotide coupling group or they are not both a solid support;
R4 is independently a phosphodiester linkage or a phosphodiester substitute linkage, wherein R4 is bonded to one 2′
or 3′
position in the structure (2) oligonucleotide and the adjacent 2′
or 3′
position in structure (2) is substituted with R21;
R21 is independently —
H, —
OH, halogen or a moiety that enhances the oligonucleotide against nuclease cleavage;
R37 is independently —
O—
, —
CH2—
, or —
CF2—
;
n is an integer from 0 to 98; and
B is independently a purine or pyrimidine base or a protected derivative thereof, provided that at least one B is a base of structure (3);
-
-
30. The compound of claim 29 wherein R4 is independently 3′
- -O—
P(S)(S)—
O-5′
, 3′
-O—
P(S)(O)—
O-5′
, 3′
-O—
P(O)(O)—
O-5′
, 3′
-O—
P(Me)(O)—
O-5′
, 3′
-NH—
P(O)(O)—
O-5′
, 2′
-S—
CH2—
O-5′
, 3′
-O—
CH2—
O-5′
, 2′
-O—
CH2—
O-5′
, 3′
-O—
P(Me)(S)—
O-5′
, 3′
-CH2—
N(CH3)—
O-5′
, or 3′
R38—
P(N(R40)2)(O)—
O-5′
, whereinR38 independently is —
O—
, —
CH2—
, or —
NH—
;
R40 independently is hydrogen, C1-C12 alkyl, C1-C12 substituted alkyl, a protecting group or both R40 together with the nitrogen atom to which they are attached form;
or both R40 together are a protecting group.
- -O—
-
31. The compound of claim 29 wherein R3 is independently —
- H, —
CH3, —
CH2CH3, —
(CH2)w—
N(R33)2 or a protecting group, or both R3 together are a protecting group,R5 is independently H or a protecting group;
R6 is independently —
S—
, —
NR5—
, —
O—
or —
CH2—
;
R7 is independently linear alkyl having 1, 2, 3 or 4 carbon atoms optionally substituted with one —
CH═
CH—
, —
C═
C—
or —
CH2—
O—
CH2—
moiety, or R7 is cyclic alkyl having 3, 4 or 5 carbon atoms, wherein one of the linear alkyl carbon atoms is optionally substituted with a single —
CH3, —
CN, ═
O, —
OH or protected hydroxyl, provided that the carbon atoms in any —
CH═
CH—
or —
CH2—
O—
CH2—
moiety are not substituted with ═
O, —
OH or protected hydroxyl;
R8 is linear alkylene having 1 or 2 carbon atoms wherein one alkylene carbon atom is optionally substituted with a single —
CH3, —
CN, ═
O, —
OH or protected hydroxyl, or R8 is absent;
R28 is independently —
CH2—
, —
CH(CH3)—
, —
CH(OCH3)—
, —
CH(OR5)—
or —
O—
, but both are not —
O—
;
R29 is independently —
N—
, —
N(CH3)—
, —
CH—
, —
C(CH3)—
, but both are not —
N(CH3)—
;
R30 is —
H or —
N(R3)2;
R31 is the side chain of an amino acid;
R33 is independently —
H, —
CH3, —
CH2CH3 or a protecting group;
R35 is H, C1-C4 alkyl or a protecting group;
R36 is H, —
CH3, —
CH2CH3, a protecting group or an optionally protected monosaccharide;
t is 1, 2, 3 or 4, but when R6 is —
O—
, —
S—
or —
NR5—
, t is 2, 3 or 4;
v is independently 0, 1 or 2; and
w is independently 1 or 2.
- H, —
-
32. The compound of claim 31 wherein R3 independently is —
- H, —
CH3, —
C2H5 or a protecting group.
- H, —
-
33. The compound of claim 29 wherein R2 is independently —
- H, —
OH, halogen, protected hydroxyl, —
O-methyl, O-ethyl, O-n-propyl, O-allyl, —
O—
(CH2)2—
OH, —
O—
(CH2)3—
OH, —
O—
(CH2)2—
F, —
O—
(CH2)s—
F, —
O—
(CH2)s—
R65, —
O—
(CH2)2—
(O—
(CH2)2)r—
R65, —
O—
(CH2)r—
O—
(CH2)r—
O—
(CH2)rR65, —
NH-methyl, —
NH-ethyl, —
NH-n-propyl, —
NH—
(CH2)2OH, —
NH—
(CH2)3OH, —
NH—
(CH2)s—
R65, —
S-methyl, —
S-ethyl, —
S-n-propyl, —
S-allyl, —
S—
(CH2)2—
OH, —
S—
(CH2)3—
OH, —
S—
(CH2)2—
F, —
S—
(CH2)s—
R65, or —
S—
(CH2)2—
(O—
(CH2)2)r—
R65, wherein;R65 is —
H, —
F, —
OH, —
OCH3, —
NH2, —
SH, protected hydroxyl, protected amino or protected thiol;
r is 1, 2, 3, or 4; and
s is 2, 3, 4, 5, 6, 7 or 8.
- H, —
-
34. The compound of claim 33 wherein R21 is independently —
- H, —
OH, —
F, protected hydroxyl, —
OCH3, —
O—
CH2CH3, —
O—
CH2CH2OH, —
O—
CH2CH2F, —
O—
CH2CH2CH3, —
O—
CH2CH2CH2OH, —
O—
CH2CH2CH2F, —
O—
CH2CF2H, —
O—
CH2CF3 or —
O—
CH2CH2—
O—
CH3.
- H, —
-
35. The compound of claim 29 wherein B independently are selected from the group consisting of a base of structure (3), guanosine, adenine, thymine, uracil, cytosine, 5-methylcytosine, 5-(1-propynyl)uracil, 5-(1-propynly)cytosine, 5-(1-butynyl)uracil or 5-(1-butynyl)cytosine.
-
36. The compound of claim 29 wherein D1 is H-phosphonate, a methylphosphonamidite, a β
- -cyanoethylphosphoramidite or a phosphoramidite.
-
41. A compound according to claim 24 having a structure selected from the group consisting of:
-
wherein R1 is an oligonucleotide, a protecting group, a linker or H.
-
-
37. A compound having the structure (4)
or tautomers, solvates or salts thereof wherein, R1 is an oligonucleotide, a protecting group, a linker or — - H;
R2 is —
R6—
(CH2)tNR5C(NR5)N(R3)2;
R3 is independently —
H, —
CH3, —
CH2CH3, —
(CH2)w—
N(R33)2 or a protecting group, or both R3 together are a protecting group;
R5 independently H or a protecting group;
R6 is independently —
S—
, —
NR5—
, —
O—
, —
CH2—
;
R33 is independently —
H, —
CH3, —
CH2CH3 or a protecting group;
each R27 is, independently —
CH═
, —
N═
, —
C(C1-C8 alkyl)═
or —
C(halogen)═
, with the proviso that no two adjacent groups R27 are both —
N═
;
or alternatively adjacent R27 are taken together to form a ring having the structure;
wherein each Ra is, independently —
CH═
, —
N═
, —
C(C1-8 alkyl)═
or —
C(halogen)═
, with the proviso that no two adjacent groups Ra are both —
N═
;
t is 1, 2, 3, or 4;
w is independently 1 or 2;
R24 is a halogen; and
R25 is —
SH, —
OH, ═
S or ═
O.- View Dependent Claims (38, 39, 40)
- H;
Specification