- INHIBITORS OF ENL/AF9 YEATS
-
Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.
- -
-
Paragraph 00137; 00139
(2021/06/26)
-
- FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1
-
The present invention relates to compounds of formula I wherein A1, A2 R4 and Q are as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.
- -
-
-
- New antimitotic agents with activity in multi-drug-resistant cell lines and in vivo efficacy in murine tumor models
-
During a screen for compounds that could inhibit cell proliferation, a series of new tubulin-binding compounds was identified with the discovery of oxadiazoline 1 (A-105972). This compound showed good cytotoxic activity against non-multi-drug-resistant and multi-drug-resistant cancer cell lines, but its utility in vivo was limited by a short half-life. Medicinal chemistry efforts led to the discovery of indolyloxazoline 22g (A-259745), which maintained all of the in vitro activity seen with oxadiazoline 1, but also demonstrated a better pharmacokinetic profile, and dose-dependent in vivo activity. Over a 28 day study, indolyloxazoline 22g increased the life span of tumor-implanted mice by up to a factor of 3 upon oral dosing. This compound, and others of its structural class, may prove to be useful in the development of new chemotherapeutic agents to treat human cancers.
- Szczepankiewicz,Chiou,Credo,Alder,Nukkala,Zielinski,Jarvis,Mollison,Frost,Bauch,Hui,Liu,Claiborne,Li,Rosenberg,Jae,Tasker,Gunawardana,Von Geldern,Gwaltney II,Wu-Wong,Gehrke
-
p. 4416 - 4430
(2007/10/03)
-
- Heterocyclic esters of rapamycin
-
A compound of the structure STR1 wherein R and R1 are each, independently, STR2 or hydrogen, R2 is a heterocyclic radical which may be optionally substituted; n=0-6; with the proviso that R and R1 are both not hydrogen, or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.
- -
-
-
