| Autor: |
Kattar SD; Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. sam_kattar@merck.com, Surdi LM, Zabierek A, Methot JL, Middleton RE, Hughes B, Szewczak AA, Dahlberg WK, Kral AM, Ozerova N, Fleming JC, Wang H, Secrist P, Harsch A, Hamill JE, Cruz JC, Kenific CM, Chenard M, Miller TA, Berk SC, Tempest P |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Feb 15; Vol. 19 (4), pp. 1168-72. Date of Electronic Publication: 2008 Dec 25. |
| DOI: |
10.1016/j.bmcl.2008.12.083 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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