Identification of a tunable site in bryostatin analogs: C20 Bryologs through late stage diversification

Org Lett. 2005 Mar 17;7(6):1177-80. doi: 10.1021/ol0501931.

Abstract

[structure: see text] The C20 region of our bryostatin analogs was identified as a nonpharmacophoric site that could be varied to tune analogs for function and physical properties without significantly affecting their binding affinity for PKC. The use of this site in a late-stage diversification strategy has enabled the facile synthesis of a variety of new C20 analogs, all of which retain nanomolar affinity for PKC, in agreement with our pharmacophore hypothesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry*
  • Brain / enzymology
  • Bryostatins
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry*
  • Models, Molecular*
  • Molecular Structure
  • Protein Kinase C / metabolism*
  • Rats
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Bryostatins
  • Macrolides
  • bryostatin 1
  • Protein Kinase C