Bryostatin compounds and methods of preparing the same

Patent metadata

Field	Value
Publication number	US-11746105-B2
Application number	US-202117162554-A
Country	US
Kind code	B2
Filing date	Jan 29, 2021
Priority date	Oct 5, 2016
Publication date	Sep 5, 2023
Grant date	Sep 5, 2023

Abstract

Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.

First claim

What is claimed is:

1. A bryostatin analog having the formula (XXXI):

wherein:
R 4 is an alkyl or a substituted alkyl;
Z 2 is CR 5 R 6 or NR 7 when the covalent bond designated “b” is a double bond;
Z 2 is OR 8 or N(R 7 ) 2 when the covalent bond designated “b” is a single bond;
R 5 is alkyloxycarbonyl, substituted alkyloxycarbonyl, alkyl or substituted alkyl;
R 6 , R 7 and R 8 are each independently H, alkyloxycarbonyl, substituted alkyloxycarbonyl, alkyl or substituted alkyl;
R 11 is a substituted acyl, an alkyl or a substituted alkyl;
R 12 is H, an alkyl or a substituted alkyl;
R 13 is H, an alkyl or a substituted alkyl; and
R 14 and R 15 are independently H, a hydroxyl protecting group or a promoiety;
or a solvate, hydrate or prodrug form thereof and/or a salt thereof.

2. The bryostatin analog of claim 1 , wherein R 14 is a promoiety.

3. A pharmaceutical composition comprising a therapeutically effective amount of a bryostatin analog of claim 1 and a pharmaceutically acceptable vehicle.

Assignees

• Univ Leland Stanford Junior

Inventors

• Wender Paul
• Quiroz Ryan
• Ho Stephen
• Shimizu Akira
• Ryckbosch Steven
• Stevens Matthew C
• Jeffreys Matthew S
• Hardman Clayton
• Sloane Jack

Classifications

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07D407/14 Primary

  containing three or more hetero rings · CPC title

• A61K31/351

  not condensed with another ring · CPC title

• A61K31/365

  Lactones · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title