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Computer-guided design, synthesis, and protein kinase C affinity of a new salicylate-based class of bryostatin analogs.

ABSTRACT: Bryostatin 1 is in clinical trials for the treatment of cancer and Alzheimer's disease and is a candidate for a first-in-class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a function oriented synthesis strategy, a new class of bryostatin-inspired analogs was designed with a simplified salicylate-derived subunit, enabling step-economical synthesis (23 total steps) of agents exhibiting bryostatin-like affinity to protein kinase C (PKC).

SUBMITTER: Wender PA

PROVIDER: S-EPMC4334246 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Computer-guided design, synthesis, and protein kinase C affinity of a new salicylate-based class of bryostatin analogs.

Wender Paul A PA Nakagawa Yu Y Near Katherine E KE Staveness Daryl D

Organic letters 20140919 19

Bryostatin 1 is in clinical trials for the treatment of cancer and Alzheimer's disease and is a candidate for a first-in-class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a function oriented synthesis strategy, a new class of bryostatin-inspired analogs was designed with a simplified salicylate-derived subunit, enabling step-economical synthesis (23 total steps) of agents exhibiting bryostatin-like affinity to protein kinase C (P ...[more]

PMID: 25238583

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Improved protein kinase C affinity through final step diversification of a simplified salicylate-derived bryostatin analog scaffold.

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Design, synthesis, and evaluation of potent bryostatin analogs that modulate PKC translocation selectivity.

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Design, Synthesis, and Docking Studies of New Torin2 Analogs as Potential ATR/mTOR Kinase Inhibitors.

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