Therapeutic phosphonate derivatives
First Claim
Patent Images
1. A compound of formula I or II wherein:
- A0 is A1;
A1 is;
A3 is;
Y1 is independently O, S, N(Rx), N(ORx), or N(N(Rx)(Rx));
Y2 is independently a bond, O, N(Rx), N(ORx), N(N(Rx)(Rx)), or —
S(O)M2—
; and
when Y2 joins two phosphorous atoms Y2 can also be C(R2)(R2);
Rx is independently H, R2, W3, a protecting group, or the formula;
Ry is independently H, W3, R2 or a protecting group;
R1 is independently H or alkyl of 1 to 18 carbon atoms;
R2 is independently H, R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups;
R3 is R3a, R3b, R3c or R3d, provided that when R3 is bound to a heteroatom, then R3 is R3c or R3d;
R3a is F, Cl, Br, I, —
CN, N3 or —
NO2;
R3b is Y1;
R3c is —
Rx, —
N(Rx)(Rx), —
SRx, —
S(O)Rx, —
S(O)2Rx, —
S(O)(ORx), —
S(O)2(ORx), —
OC(Y1)Rx, —
OC(Y1)ORx, —
OC(Y1)(N(Rx)(Rx)), —
SC(Y1)Rx, —
SC(Y1)ORx, —
SC(Y1)(N(Rx)(Rx)), —
N(Rx)C(Y1)Rx, —
N(Rx)C(Y1)ORx, or —
N(Rx)C(Y1)(N(Rx)(Rx));
R3d is —
C(Y1)Rx, —
C(Y)ORx or —
C(Y)(N(Rx)(Rx));
R4 is an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms;
R5 is R4 wherein each R4 is substituted with 0 to 3 R3 groups;
R5a is independently alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2-18 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R3 groups;
W3 is W4 or W5;
W4 is R5, —
C(Y1)R5, —
C(Y1)W5, —
SO2R5, or —
SO2W5;
W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups;
W6 is W3 independently substituted with 1, 2, or 3 A3 groups;
M2 is 0, 1 or 2;
M12a is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
M12b is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
M1a, M1c, and M1d are independently 0 or 1;
M12c is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; and
R20 is ethyl or vinyl.
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Abstract
Phosphorus substituted mycophenolate derivatives with anti-cancer, anti-viral, anti-inflammatory and anti-tissue/organ transplant rejection properties having use as therapeutics and for other industrial purposes are disclosed. The compositions inhibit tumor growth, viral growth, inflammation, and tissue/organ transplant rejection and/or are useful therapeutically for the treatment or prevention of cancer, viral infection, inflammation and tissue/organ transplant rejection, as well as in assays for the detection of cancer, viral infection, inflammation and tissue/organ transplant rejection.
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Citations
32 Claims
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1. A compound of formula I or II
wherein: -
A0 is A1;
A1 is;
A3 is;
Y1 is independently O, S, N(Rx), N(ORx), or N(N(Rx)(Rx));
Y2 is independently a bond, O, N(Rx), N(ORx), N(N(Rx)(Rx)), or —
S(O)M2—
; and
when Y2 joins two phosphorous atoms Y2 can also be C(R2)(R2);
Rx is independently H, R2, W3, a protecting group, or the formula;
Ry is independently H, W3, R2 or a protecting group;
R1 is independently H or alkyl of 1 to 18 carbon atoms;
R2 is independently H, R3 or R4 wherein each R4 is independently substituted with 0 to 3 R3 groups;
R3 is R3a, R3b, R3c or R3d, provided that when R3 is bound to a heteroatom, then R3 is R3c or R3d;
R3a is F, Cl, Br, I, —
CN, N3 or —
NO2;
R3b is Y1;
R3c is —
Rx, —
N(Rx)(Rx), —
SRx, —
S(O)Rx, —
S(O)2Rx, —
S(O)(ORx), —
S(O)2(ORx), —
OC(Y1)Rx, —
OC(Y1)ORx, —
OC(Y1)(N(Rx)(Rx)), —
SC(Y1)Rx, —
SC(Y1)ORx, —
SC(Y1)(N(Rx)(Rx)), —
N(Rx)C(Y1)Rx, —
N(Rx)C(Y1)ORx, or —
N(Rx)C(Y1)(N(Rx)(Rx));
R3d is —
C(Y1)Rx, —
C(Y)ORx or —
C(Y)(N(Rx)(Rx));
R4 is an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms;
R5 is R4 wherein each R4 is substituted with 0 to 3 R3 groups;
R5a is independently alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2-18 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R3 groups;
W3 is W4 or W5;
W4 is R5, —
C(Y1)R5, —
C(Y1)W5, —
SO2R5, or —
SO2W5;
W5 is carbocycle or heterocycle wherein W5 is independently substituted with 0 to 3 R2 groups;
W6 is W3 independently substituted with 1, 2, or 3 A3 groups;
M2 is 0, 1 or 2;
M12a is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
M12b is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
M1a, M1c, and M1d are independently 0 or 1;
M12c is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; and
R20 is ethyl or vinyl. - 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, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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Specification