We claim:
1. A compound of Formula I
240
where:
A and B are independently O or S;
X and Y are both hydrogen or, taken together, form a bond;
R1 is hydrogen or C1-C4 alkyl;
R2 is optionally up to two substituents independently selected from the group consisting of halo, cyano, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkoxy, aryloxy, benzyloxy, C1-C6 alkylthio and arylthio;
R3 is a substituent optionally selected from the group consisting of aryl, heteroaryl, CH2NH-(1-deoxy–D-glucose), and (CH2)m-Z;
R4 is hydrogen, C1-C4 alkyl, (CH2)m-Z, or 2-deoxy–D-ribofuranos-1-yl;
R5 is optionally up to two substituents independently selected from the group consisting of halo, cyano, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkoxy, aryloxy, benzyloxy, C1-C6 alkylthio and arylthio;
R6 is optionally up to three substituents selected from C1-C4 alkyl;
R7 is a substituent optionally selected from (C1-C6 alkoxy)carbonyl or (CH2)m-Z;
Z is halo, hydroxy, (C1-C6 alkyl)3SiO, (diphenyl) (C1-C6 alkyl)SiO, carboxy, (C1-C4 alkoxy)carbonyl, or NR8R9;
R8 is hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl;
R9 is hydrogen, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkanoyl, substituted C1-C6 alkanoyl, tert-butoxycarbonyl, benzyloxycarbonyl, an amino acid residue, a protected amino acid residue, -(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl; or
R8 and R9 taken together with the nitrogen to which they are attached form a saturated heterocycle optionally substituted with one or two hydroxy, amino, or C1-C6 alkyl groups;
Q1 is O, S(O)n or (CH2)1-3;
Q2 is a carbon-carbon single bond, a carbon-carbon double bond, NR10, or NR10CHR11;
Q3 is (CH2)1-3;
R10 is hydrogen, (C1-C6 alkyl)sulfonyl, arylsulfonyl, hetroarylsulfonyl, C1-C6 alkyl, substituted C1-C6 alkyl, (C1-C5 alkyl)carbonyl, substituted (C1-C5 alkyl)carbonyl, an amino acid residue, a protected amino acid residue, -(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl;
R11 is hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl; or R10 and R11 taken together with the atoms to which they are attached form a 5- or 6-membered saturated heterocycle;
m is 0, 1, 2, 3, 4, or 5;
n is 0, 1, or 2; or a pharmaceutically acceptable salt thereof.
2. A compound of claim 1 where X and Y, taken together, form a bond.
3. A compound of claim 1 or 2 where Q2 is a carbon-carbon single bond.
4. A compound of claim 1 or 2 where Q2 is NR10.
5. A compound of claim 4 where R10 is hydrogen.
6. A compound of claim 1 or 2 where Q2 is NR10CHR11.
7. A compound of claim 6 where R10 is hydrogen.
8. A pharmaceutical formulation comprising a compound of Formula I
241
where:
A and B are independently O or S;
X and Y are both hydrogen or, taken together, form a bond;
R1 is hydrogen or C1-C4 alkyl;
R2 is optionally up to two substituents independently selected from the group consisting of halo, cyano, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkoxy, aryloxy, benzyloxy, C1-C6 alkylthio and arylthio;
R3 is a substituent optionally selected from the group consisting of aryl, heteroaryl, CH2NH-(1-deoxy–D-glucose), and (CH2)m-Z;
R4 is hydrogen, C1-C4 alkyl, (CH2)m-Z, or 2-deoxy–D-ribofuranos-1-yl;
R5 is optionally up to two substituents independently selected from the group consisting of halo, cyano, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkoxy, aryloxy, benzyloxy, C1-C6 alkylthio and arylthio;
R6 is optionally up to three substituents selected from C1-C4 alkyl;
R7 is a substituent optionally selected from (C1-C6 alkoxy)carbonyl or (CH2)m-Z;
Z is halo, hydroxy, (C1-C6 alkyl)3SiO, (diphenyl) (C1-C6 alkyl)SiO, carboxy, (C1-C4 alkoxy)carbonyl, or NR8R9;
R8 is hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl;
R9 is hydrogen, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkanoyl, substituted C1-C6 alkanoyl, tert-butoxycarbonyl, benzyloxycarbonyl, an amino acid residue, a protected amino acid residue, -(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl; or
R8 and R9 taken together with the nitrogen to which they are attached form a saturated heterocycle optionally substituted with one or two hydroxy, amino, or C1-C6 alkyl groups;
Q1 is O, S(O)n or (CH2)1-3;
Q2 is a carbon-carbon single bond, a carbon-carbon double bond, NR10 or NR10CHR11;
Q3 is (CH2)1-3;
R10 is hydrogen, (C1-C6 alkyl)sulfonyl, arylsulfonyl, hetroarylsulfonyl, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, (C1-C5 alkyl)carbonyl, substituted (C1-C5 alkyl)carbonyl, an amino acid residue, a protected amino acid residue, -(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl;
R11 is hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl; or R10 and R11 taken together with the atoms to which they are attached form a 5- or 6-membered saturated heterocycle;
m is 0, 1, 2, 3, 4, or 5;
n is 0, 1, or 2; or a pharmaceutically acceptable salt thereof.
9. A method for inhibiting CDK4, comprising administering to a mammal in need of said inhibition an effective amount of a compound of Formula I
242
where:
A and B are independently O or S;
X and Y are both hydrogen or, taken together, form a bond;
R1 is hydrogen or C1-C4 alkyl;
R2 is optionally up to two substituents independently selected from the group consisting of halo, cyano, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkoxy, aryloxy, benzyloxy, C1-C6 alkylthio and arylthio;
R3 is a substituent optionally selected from the group consisting of aryl, heteroaryl, CH2NH-(1-deoxy–D-glucose), and (CH2)m-Z;
R4 is hydrogen, C1-C4 alkyl, (CH2)m-Z, or 2-deoxy–D-ribofuranos-1-yl;
R5 is optionally up to two substituents independently selected from the group consisting of halo, cyano, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkoxy, aryloxy, benzyloxy, C1-C6 alkylthio and arylthio;
R6 is optionally up to three substituents selected from C1-C4 alkyl;
R7 is a substituent optionally selected from (C1-C6 alkoxy)carbonyl or (CH2)m-Z;
Z is halo, hydroxy, (C1-C6 alkyl)3SiO, (diphenyl) (C1-C6 alkyl)SiO, carboxy, (C1-C4 alkoxy)carbonyl, or NR8R9;
R8 is hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl;
R9 is hydrogen, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, C1-C6 alkanoyl, substituted C1-C6 alkanoyl, tert-butoxycarbonyl, benzyloxycarbonyl, an amino acid residue, a protected amino acid residue, -(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl; or
R8 and R9 taken together with the nitrogen to which they are attached form a saturated heterocycle optionally substituted with one or two hydroxy, amino, or C1-C6 alkyl groups;
Q1 is O, S(O)n or (CH2)1-3;
Q2 is a carbon-carbon single bond, a carbon-carbon double bond, NR10 or NR10CHR11;
Q3 is (CH2)1-3;
R10 is hydrogen, (C1-C6 alkyl)sulfonyl, arylsulfonyl, hetroarylsulfonyl, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl, (C1-C5 alkyl)carbonyl, substituted (C1-C5 alkyl)carbonyl, an amino acid residue, a protected amino acid residue, -(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl;
R11 is hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl, C1-C6 alkenyl, substituted C1-C6 alkenyl; or R10 and R11 taken together with the atoms to which they are attached form a 5- or 6-membered saturated heterocycle;
m is 0, 1, 2, 3, 4, or 5;
n is 0, 1, or 2; or a pharmaceutically acceptable salt thereof.
10. A method of claim 9 where the mammal is a human.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A reflective extreme ultraviolet (EUV) mask comprising:
a mask substrate;
a patterned structure on the mask substrate; and
a non-patterned structure on the mask substrate,
wherein at least one of the patterned structure and the non-patterned structure include a thermally treated region configured to control a reflectivity of the respective patterned and non-patterned structures.
2. The reflective EUV mask of claim 1, wherein the patterned structure comprises:
a reflective layer on the mask substrate; and
an absorbing layer pattern on the reflective layer, the absorbing layer pattern having openings configured to expose the reflective layer.
3. The reflective EUV mask of claim 2, wherein the reflective layer includes a plurality of layers of molybdenum and silicon alternately stacked.
4. The reflective EUV mask of claim 2, wherein the thermally treated region is in at least a portion of the reflective layer exposed through at least one of the openings, the thermally treated region locally controlling reflectivities of the reflective layer exposed through the at least one opening.
5. The reflective EUV mask of claim 1, wherein the non-patterned structure comprises:
a reflective layer on the mask substrate; and
an absorbing layer on the reflective layer,
wherein at least a portion of the thermally treated region is in a vertical direction in the absorbing layer and the reflective layer.
6. The reflective EUV mask of claim 1, wherein the patterned structure is centrally located on the mask substrate and the non-patterned structure is located at an edge portion of the mask substrate surrounding the patterned structure.
7. The reflective EUV mask of claim 4, wherein a width of the opening including the thermally treated region is wider than a width of an opening not including a thermally treated region.
8-17. (canceled)