Claims
- 1. A compound of Formula I 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; R5 and R5′ are 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 and R6′ are optionally up to three substituents independently selected from C1-C4 alkyl; R7 and R7′ are optionally substituents independently 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, β-(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 and Q6 are independently O, S(O)n or —(CH2)1-3—; Q2 and Q5 are independently selected from a carbon-carbon single bond, a carbon-carbon double bond, —NR10—, or —NR10—CHR11—; Q3 and Q4 are independently selected from —(CH2)1-3—; R10 is independently at each occurance 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, β-(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl; R11 is independently at each occurance 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 independently at each occurance 0, 1, 2, 3, 4, or 5; n is independently at each occurance 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 Q5 is —NR10—.
- 5. A compound of claim 1 or 2 where Q5 is —NR10—CHR11—.
- 6. A compound of claim 4 where R10 is hydrogen.
- 7. A compound of claim 5 where R10 is hydrogen.
- 8. A pharmaceutical formulation comprising a compound of Formula I 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; R5 and R5′ are 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 and R6′ are optionally up to three substituents independently selected from C1-C4 alkyl; R7 and R7′ are optionally substituents independently 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, β-(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 and Q6 are independently O, S(O)n or —(CH2)1-3—; Q2 and Q5 are independently selected from a carbon-carbon single bond, a carbon-carbon double bond, —NR10—, or —NR10—CHR11—; Q3 and Q4 are independently selected from —(CH2)1-3—; R10 is independently at each occurance 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, β-(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl; R11 is independently at each occurance 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 independently at each occurance 0, 1, 2, 3, 4, or 5; n is independently at each occurance 0, 1, or 2; or a pharmaceutically acceptable salt thereof.
- 9. A method for inhibiting CDK4, comprisingadministering to a mammal in need of said inhibition an effective amount of a compound of Formula I 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; R5 and R5′ are 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 and R6′ are optionally up to three substituents independently selected from C1-C4 alkyl; R7 and R7′ are optionally substituents independently 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, β-(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 and Q6 are independently O, S(O)n or —(CH2)1-3—; Q2 and Q5 are independently selected from a carbon-carbon single bond, a carbon-carbon double bond, —NR10—, or —NR10—CHR11—; Q3 and Q4 are independently selected from —(CH2)1-3—; R10 is independently at each occurance 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, β-(pyridinyl)alaninyl, aryl, heteroaryl, arylcarbonyl, or heteroarylcarbonyl; R11 is independently at each occurance 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 independently at each occurance 0, 1, 2, 3, 4, or 5; n is independently at each occurance 0, 1, or 2; or a pharmaceutically acceptable salt thereof.
- 10. A method of claim 9 where the mammal is a human.
Parent Case Info
This application is the U.S. National Stage filing of PCT/US00/33274, filed Dec. 18, 2000, which claims the benefit of U.S. Provisional Applications Serial Nos. 60/171,219, filed on Dec. 16, 1999, and 60/171,269, filed on Dec. 16, 1999.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US00/33274 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO01/44235 |
6/21/2001 |
WO |
A |
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5591855 |
Hudkins et al. |
Jan 1997 |
A |
5856517 |
Dalton et al. |
Jan 1999 |
A |
Foreign Referenced Citations (1)
Number |
Date |
Country |
WO9517182 |
Jun 1995 |
WO |
Provisional Applications (2)
|
Number |
Date |
Country |
|
60/171219 |
Dec 1999 |
US |
|
60/171269 |
Dec 1999 |
US |