US 12,435,071 B2
Bryostatin compounds and methods of preparing the same
Paul Wender, Menlo Park, CA (US); Ryan Quiroz, Boston, MA (US); Stephen Ho, Stanford, CA (US); Akira Shimizu, Stanford, CA (US); Steven Ryckbosch, Albany, CA (US); Matthew C. Stevens, Atherton, CA (US); Matthew S. Jeffreys, King of Prussia, PA (US); Clayton Hardman, Stanford, CA (US); and Jack Sloane, Stanford, CA (US)
Assigned to The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US)
Filed by The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US)
Filed on Sep. 1, 2023, as Appl. No. 18/241,636.
Application 17/162,554 is a division of application No. 16/337,221, granted, now 10,947,221, issued on Mar. 16, 2021, previously published as PCT/US2017/054158, filed on Sep. 28, 2017.
Application 18/241,636 is a continuation of application No. 17/162,554, filed on Jan. 29, 2021, granted, now 11,746,105.
Claims priority of provisional application 62/404,687, filed on Oct. 5, 2016.
Prior Publication US 2024/0116908 A1, Apr. 11, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 407/14 (2006.01); A61K 31/351 (2006.01); A61K 31/365 (2006.01); A61P 25/28 (2006.01); A61P 31/18 (2006.01); A61P 35/00 (2006.01); C07D 493/22 (2006.01)
CPC C07D 407/14 (2013.01) [A61K 31/351 (2013.01); A61K 31/365 (2013.01); A61P 25/28 (2018.01); A61P 31/18 (2018.01); A61P 35/00 (2018.01); C07D 493/22 (2013.01)] 7 Claims
 
1. A method of treating cancer, the method comprising:
administering a therapeutically effective amount of a pharmaceutical composition comprising a bryostatin analog and a pharmaceutically acceptable vehicle to an individual in need thereof,
wherein the bryostatin analog has the formula (XXXIV):

OG Complex Work Unit Chemistry
wherein:
W1 is an alkenyl, a substituted alkenyl, an alkynyl, a substituted alkynyl, an allenyl, a substituted allenyl, an alkyl, a substituted alkyl, an aryl, a substituted aryl, a heteroaryl, a substituted heteoraryl, heteroalkyl, substituted heteroalkyl, heterocycle, substituted heterocycle, a carbon chain containing oxygen or nitrogen atoms, a cycloalkyl, a cycloalkenyl, or polyethylene glycol (PEG) group;
Z2 is CR5R6 or NR7 when the covalent bond designated “b” is a double bond;
Z2 is OR8, a phosphate, a phosphoryl, a thio group, a sulfate, a sulfonyl, an organoselenium group, or N(R7)2 when the covalent bond designated “b” is a single bond;
R5 is halogen, alkyloxycarbonyl, substituted alkyloxycarbonyl, alkyl or substituted alkyl;
R6, R7 and R8 are each independently H, halogen, alkyloxycarbonyl, substituted alkyloxycarbonyl, alkyl or substituted alkyl;
X1 is H or OR11,
X4 and X5 are independently selected from H, halogen, alkyl, substituted alkyl, alkoxy, amine, substituted amine, amide, substituted amide, acyl, hydroxyl, heteroalkyl, heteroaryl, substituted heteroalkyl, substituted heteroaryl, phosphate, organoselenium, thio, substituted thio;
Y1 is OMe;
R11 is H, an acyl, a substituted acyl, an alkyl, a substituted alkyl, or CO-aryl, or CO-heteroaryl and substituted versions thereof;
R12 is H, an alkyl or a substituted alkyl;
R13 is H, an alkyl or a substituted alkyl; and
R16 is H, an alkyl or a substituted alkyl,
R14 and R15 are independently H, a hydroxyl protecting group or a promoiety;
or a solvate, hydrate or prodrug form thereof and/or a salt thereof.