Phosphorus-containing compounds and uses thereof
1 Assignment
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Accused Products
Abstract
This invention concerns a new family of phosphorus-containing compounds containing a moiety JQA- in which:
A is absent or is —O—, —S— or —NR2—;
Q is absent or (if A is —O—, —S— or —NR2—) Q may be —V—, —OV—, —SV—, or —NR2V—, where V is an aliphatic, heteroaliphatic, aryl, or heteroaryl moiety, such that J is linked to the cyclohexyl ring directly, through A or through VA, OVA, SVA or NR2VA;
K is O or S;
each occurrence of Y is independently —O—, —S—, —NR2—, or a bond linking a R5 moiety to P;
each occurrence of R and R is independently an aliphatic, heteroaliphatic, aryl, or heteroaryl moiety, or H; and
each occurrence of R6 is independently —PK(YR5)(YR5), —SO2(YR5) or —C(O)(YR5); so long as any R or R5 moiety linked directly to P is not H;
wherein two R2, R5 and/or R6 moieties may be chemically linked to one another to form a ring;
each occurrence of G is independently —O—, —S—, —NR2— or (M)x;
each occurrence of M is independently a substituted or unsubstituted methylene moiety, and any M-M′ moiety may be saturated or unsaturated;
each occurrence of x is independently an integer from 1-6; and the other variables are as defined herein.
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Citations
39 Claims
- 1. A compound of the formula:
- 2. A compound of the formula:
- 3. A compound of the formula:
- 4. A compound of the formula:
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22. A compound comprising a derivative of rapamycin or 43-epi-rapamycin in which the hydroxyl group at position 43 is replaced by a group JQA-, wherein:
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A is —
O—
, —
S—
or —
NR2—
or is absent;
Q is absent or (if A is —
O—
, —
S—
or —
NR2—
) Q may be —
V—
, —
OV—
, —
SV—
, or —
NR2V—
, where V is an aliphatic, heteroaliphatic, aryl, or heteroaryl moiety, such that J is linked to the cyclohexyl ring directly,through A or through VA, OVA, SVA or NR2VA;
K is O or S;
each occurrence of Y is independently —
O—
, —
S—
, —
NR2—
, or a bond linking a R5 moiety to P;
each occurrence of R2 and R is independently an aliphatic, heteroaliphatic, aryl, or heteroaryl moiety, or H; and
each occurrence of R6 is independently —
PK(YR5)(YR5), —
SO2(YR5) or —
C(O)(YR5);
so long as any R2 or R5 moiety linked directly to P is not H;
wherein two R2, R5 and/or R6 moieties may be chemically linked to one another to form a ring;
each occurrence of G is independently —
O—
, —
S—
, —
NR2—
or (M)x;
each occurrence of M is independently a substituted or unsubstituted methylene moiety, and any M-M′
moiety may be saturated or unsaturated;
each occurrence of x is independently an integer from 1-6;
wherein each of the foregoing aliphatic and heteroaliphatic moieties is independently linear or branched, or cyclic or acyclic, and substituted or unsubstituted, and each of the aryl, heteoraryl, acyl, aroyl or heteroaroyl moieties is independently substituted or unsubstituted;
with one or more of the following additional features;
(a) epimerization at position 28, or replacement of the position 28 hydroxyl group (in either sterochemical orientation) with halo, —
OR2 or —
OC(═
O)AR2;
(b) replacement of the ketone at position 24 with a substituted or unsubstituted oxime, or with a hydroxyl group or derivative thereof of the formula —
OR2 or —
OC(═
O)AR2;
(c) replacement of the ketone at position 24 with a substituted or unsubstituted oxime, or with a hydroxyl group or derivative thereof of the formula —
OR2 or —
OC(═
O)AR2;
(d) epimerization of the —
OMe at position 7 and/or replacement of the —
OMe with a moiety selected from H, halo, —
RA, —
ORA, —
SRA, —
OC(O)RA, —
OC(O)NRARB, —
NRARB, —
NRBC(O)RA, —
NRBC(O)ORA, —
NRBSO2RA or —
NRBSO2NRARB;
where RA is R2 and where RB is OH or R2; and
(e) elimination of the —
OMe at position 7 yielding the tetra-ene moiety;
- View Dependent Claims (23, 24, 25, 26)
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Specification