| 摘要 |
This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders. |
| 主权项 |
1. A compound of Formula:or a pharmaceutically acceptable salt thereof;wherein:
Z is —(CH2)x— or x is 1, 2, 3, or 4; z is 2, 3 or 4; y is 0, 1, 2, 3 or 4; each R1 is independently aryl, alkyl, cycloalkyl, wherein two R1s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle; R10 is —C(O)—R12, or —C(O)O—R13; R12 is NHRA or RA; R13 is RA; RA is C1-C8 alkyl, cycloalkylalkyl, -TT-RR, or C1-C8 cycloalkyl; TT is C1-C8 alkylene or C3-C8cycloalkylene linker; and RR is hydroxyl, C1-C6alkoxy, amino, C1-C6 alkylamino, di-C1-C6 alkylamino, C6-C10 aryl, heteroaryl having one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, C3-C10carbocycle, or heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O and S. |
