|
|||||
|
|
Parallel medicinal chemistry approaches to selective HDAC1/HDAC2 inhibitor (SHI-1:2) optimization |
|
| Authors: | Solomon D. Kattar Laura M. Surdi Anna Zabierek Joey L. Methot Richard E. Middleton Bethany Hughes Alexander A. Szewczak William K. Dahlberg Astrid M. Kral Nicole Ozerova Judith C. Fleming Hongmei Wang Paul Secrist Andreas Harsch Julie E. Hamill Jonathan C. Cruz Candia M. Kenific Melissa Chenard Thomas A. Miller Scott C. Berk Paul Tempest |
| Affiliation: | 1. Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA;2. Department of Cancer Biology and Therapeutics, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA;3. Department of Oncology Pharmacology, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA |
| Abstract: | The successful application of both solid and solution phase library synthesis, combined with tight integration into the medicinal chemistry effort, resulted in the efficient optimization of a novel structural series of selective HDAC1/HDAC2 inhibitors by the MRL-Boston Parallel Medicinal Chemistry group. An initial lead from a small parallel library was found to be potent and selective in biochemical assays. Advanced compounds were the culmination of iterative library design and possess excellent biochemical and cellular potency, as well as acceptable PK and efficacy in animal models. |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ | |