| 摘要 |
The invention relates to a chemotherapeutic cancer treatment in which compounds (BH3Is) are administered to a mammal to treat B-cell Lymphoma or other hematopoietic cancers, including diseases associated with MCL-1. The invention also provides a method for treating types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more disclosed compounds in combination with other therapes, for example, 26S proteasome inhibitors, such as, for example, Bortezomib. The invention also relates to autoimmune treatment with pharmaceutical compositions comprising one or more disclosed compounds. The invention also relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.;Illustrative compounds are those of Formula II:; |
| 主权项 |
1. A method for inhibiting myeloid cell leukemia 1 activity in a patient having cancer, comprising administering to said patient a compound of Formula II:or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:
R1, R3, and R6 are each hydroxy; R7 and R8 are each hydrogen; R4 and R9 are each selected from the group consisting of hydrogen, hydroxy, —(C1-C6) alkyl, —(C1-C6)alkylhydroxy, —(C1-C6)alkylamino, —(C1-C6)alkylamido, —O(C1-C6)alkylhalo, —OC(O)(C1-C6)alkyl, halo, —C(O)R, —C(O)N(R)2, and —C(O)OR; where each R is independently selected from the group consisting of hydrogen, straight or branched C1-10 alkyl, C2-10 alkenyl, or C2-10 alkynyl, C3-10 cycloalkyl, C5-8 cycloalkenyl, C7-20 arylalkyl, saturated or unsaturated 3-11 member heterocyclyl or heterocyclylalkyl containing 1, 2, 3, or 4 heteroatoms selected independently from N, O, and S. |
