Compounds, compositions and methods for cancer patient stratification and cancer treatment

Patent metadata

Field	Value
Publication number	US-12053476-B2
Application number	US-202117161612-A
Country	US
Kind code	B2
Filing date	Jan 28, 2021
Priority date	Feb 5, 2016
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

The present invention features improved compounds, especially

methods of identifying patients having cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).

First claim

What is claimed is:

1. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers or excipients and a compound having the structure:

or a pharmaceutically acceptable salt thereof.

3. A kit for decreasing cancer cell proliferation in a subject pre-selected as responsive to a PDE3A modulator, the kit comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof.

4. A method comprising the step of
reacting the racemate Compound 3a

with NaOCl in acetic acid at a temperature range form 10-15° C. (including 100 and 15°) to obtain the racemate Compound 6a

and subsequently performing a separation of enantiomers of Compound 6a to obtain Compound 6

5. A method according to claim 4 further comprising optionally in a preceding step a separation of enantiomers of Compound 3a to obtain Compound 3

and the reaction step with NaOCl in acetic acid at a temperature range form 10-15° C. (including 10° and 15°) is performed with the enantiomer Compound 3 and optionally further comprising a subsequent separation of enantiomers.

6. A method according to claim 4 whereby the enantiomer Compound 3

is reacted to obtain enantiomer Compound 6

Assignees

• Bayer Pharma AG
• Broad Inst Inc
• Dana Farber Cancer Inst Inc

Inventors

• Lewis Timothy A
• Burgin Alex
• Schenone Monica
• Wu Xiaoyun
• Greulich Heidi
• Meyerson Matthew
• De Waal Luc
• Wengner Antje Margret
• Eis Knut
• Lienau Philip
• Sack Ulrike
• Lange Martin

Classifications

• G01N33/575

  for cancer · CPC title

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61K31/50 Primary

  Pyridazines; Hydrogenated pyridazines · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title