The chemistry and biology of the bryostatins: Potential PKC inhibitors in clinical development

Current Medicinal Chemistry

Volumn 19, Issue 16, 2012, Pages 2652-2664

  Ruan, B F ^a   Zhu, H L ^b  

^a HEFEI UNIVERSITY OF TECHNOLOGY   (China)

^b NANJING UNIVERSITY   (China)

Author keywords

Alzheimer's disease; Analogue; Anti cancer; Bryostatin; Clinical; Immunity; Learning and memory; Natural products; PKC; Structure activity relationship

Indexed keywords

BRYOSTATIN; BRYOSTATIN 1; BRYOSTATIN 10; BRYOSTATIN 11; BRYOSTATIN 12; BRYOSTATIN 13; BRYOSTATIN 14; BRYOSTATIN 15; BRYOSTATIN 16; BRYOSTATIN 17; BRYOSTATIN 18; BRYOSTATIN 19; BRYOSTATIN 2; BRYOSTATIN 20; BRYOSTATIN 3; BRYOSTATIN 4; BRYOSTATIN 5; BRYOSTATIN 6; BRYOSTATIN 7; BRYOSTATIN 8; BRYOSTATIN 9; CYTARABINE; FLUDARABINE; PACLITAXEL; PROTEIN KINASE C INHIBITOR; UNCLASSIFIED DRUG; VINCRISTINE;

ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; BIOLOGY; CLINICAL TRIAL; COGNITION; CONTINUOUS INFUSION; DRUG MEGADOSE; DRUG STRUCTURE; EYE PAIN; FEVER; FLU LIKE SYNDROME; HEADACHE; HUMAN; IMMUNITY; LEARNING; MEMORY; MYALGIA; NONHODGKIN LYMPHOMA; NONHUMAN; PHLEBITIS; PHOTOPHOBIA; STRUCTURE ACTIVITY RELATION; VOMITING;

EID: 84860751562     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712800493020     Document Type: Article

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97. Wender, P.A.; Verma, V.A. Design, synthesis, and biological evaluation of a potent, PKC selective, B-ring analog of bryostatin. Org. Lett., 2006, 8, 1893-1896. (Pubitemid 43692184)
98. Wender, P.A.; Hilinski, M.K.; Mayweg, A.V.W. Late-Stage Intermolecular CH Activation for Lead Diversification: A Highly Chemoselective Oxyfunctionalization of the C-9 Position of Potent Bryostatin Analogues. Org. Lett., 2005, 7, 79-82. (Pubitemid 40138316)
99. Wender, P.A.; Horan, J.C.; Verma, V.A. Total synthesis and initial biological evaluation of new B-ring-modified bryostatin analogs. Org. Lett., 2006, 8, 5299-5302. (Pubitemid 44861552)
100. Wender, P.A.; De Christopher, B. A.; Schrier, A.J. Efficient synthetic access to a new family of highly potent bryostatin analogues via a prins-driven macrocyclization strategy. J. Am. Chem. Soc., 2008, 130, 6658-6659. (Pubitemid 351748373)
101. P.A.; Wender, Baryza, J.L.; Brenner, S.E.; De Christopher, B.A.; Loy, B.A.; Schrier, A.J.; Verma, V.A. Design, synthesis, and evaluation of potent bryostatin analogs that modulate PKC translocation selectivity. Proc. Natl. Acad. Sci. U S A., 2002, 108, 6721-6726.
102. Wender, P.A.; Verma, V.A. The design, synthesis, and evaluation of C7 diversified bryostatin analogs reveals a hot spot for PKC affinity. Org. Lett., 2008, 10, 3331-3334.
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105. Keck, G.E.; Poudel, Y.B.; Welch, D.S.; Kraft, M.B.; Truong, A.P.; Stephens, J.C.; Kedei, N.; Lewin, N.E.; Blumberg, P.M. Substitution on the A-ring confers to bryopyran analogues the unique biological activity characteristic of bryostatins and distinct from that of the phorbol esters. Org. Lett., 2009, 11, 593-596.
106. Keck, G.E.; Li, W.; Kraft, M.B.; Kedei, N.; Lewin, N.E.; Blumberg, P.M.; The bryostatin 1 A-ring acetate is not the critical determinant for antagonism of phorbol ester-induced biological responses. Org. Lett., 2009, 11, 2277-2280.
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109. Trost, B.M.; Dong, G. Total synthesis of bryostatin 16 using a Pd-catalyzed diyne coupling as macrocyclization method and synthesis of C20-epibryostatin 7 as a potent anticancer agent. J. Am. Chem. Soc., 2010, 132, 16403-16416.