Gemcitabine prodrugs

Patent metadata

Field	Value
Publication number	US-11629164-B2
Application number	US-202016865527-A
Country	US
Kind code	B2
Filing date	May 4, 2020
Priority date	Jun 25, 2014
Publication date	Apr 18, 2023
Grant date	Apr 18, 2023

Abstract

This invention relates to a prodrug of the monophosphate nucleotide of the well-known oncology drug gemcitabine. Specifically, it relates to gemcitabine-[phenyl-benzoxy- L -alaninyl)]-phosphate when present as a single phosphate diastereoisomer and, in particular, it relates to the (S)-phosphate diastereoisomer which offers a remarkable and unexpected increase in solubility relative to the (R)-diastereoisomer. The (S)-phosphate epimer is also preferentially taken up into cyclodextrin solutions over the (R)-diastereoisomer.

First claim

The invention claimed is:

1. A method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate 3:

or a pharmaceutically acceptable salt thereof, having a diastereoisomeric purity greater than 90%, wherein the cancer is selected from pancreatic cancer, ovarian cancer, lung cancer, bladder cancer, cholangiocarcinoma, renal cancer, cervical cancer, and thymic cancer.

2. The method of claim 1 , wherein gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate is not in the form of a salt.

3. The method of claim 1 , wherein the cancer is pancreatic cancer.

4. The method of claim 1 , wherein the cancer is ovarian cancer.

5. The method of claim 1 , wherein the cancer is cholangiocarcinoma.

6. The method of claim 1 , wherein gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate is administered orally.

7. The method of claim 1 , wherein gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate is administered intravenously.

8. The method of claim 1 , wherein the diastereoisomeric purity of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate is greater than 95%.

9. The method of claim 1 , wherein the diastereoisomeric purity of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate is greater than 98%.

10. The method of claim 1 , wherein the diastereoisomeric purity of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate is greater than 99.5%.

Assignees

• NuCana plc

Inventors

• Griffith Hugh
• Mcguigan Christopher
• Slusarczyk Magdalena
• Serpi Michaela
• Ferrari Valentina

Classifications

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• A61P13/10

  of the bladder · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title