17α-monoesters and 17α,21-diesters of cortexolone for use in the treatment of tumors

Patent metadata

Field	Value
Publication number	US-10646497-B2
Application number	US-201816199015-A
Country	US
Kind code	B2
Filing date	Nov 23, 2018
Priority date	Oct 8, 2014
Publication date	May 12, 2020
Grant date	May 12, 2020

Abstract

The present invention relates to certain cortexolone derivatives of formula (I)

and the use of the same as antitumor active ingredients for the curative or adjuvant, or neoadjuvant or palliative treatment of precancerous lesions, dysplasias, metaplasias and tumor diseases, including malignant neoplasias and metastasis. The present invention also relates to pharmaceutical compositions comprising cortexolone derivatives of formula (I) as active ingredients and at least one physiologically acceptable excipient, and to the use of the pharmaceutical compositions as antitumor medicinal products.

First claim

What is claimed is:

1. A method of treating a tumor disease in a subject in need thereof, comprising administrating to said subject a therapeutically effective amount of a compound of formula (I):

wherein:
R is C(O)—R 1 ;
R 1 is hydrogen or a linear alkyl chain containing 2 to 5 carbon atoms;
R′ is a linear alkyl chain containing 3 to 6 carbon atoms or an optionally substituted aryl group or an optionally substituted heteroaryl group; and
wherein R 1 and R′ are not the same, and

wherein the tumor disease is an adenocarcinoma.

2. The method of claim 1 , wherein the adenocarcinoma is prostate carcinoma, pancreatic carcinoma, exocrine pancreatic carcinoma, colon carcinoma or mammary carcinoma.

3. The method of claim 2 , wherein the prostate carcinoma is or becomes resistant to anti-androgen targeted therapy.

4. The method of claim 3 , wherein the anti-androgen targeted therapy is enzalutamide.

5. The method of claim 2 , wherein the mammary carcinoma is triple negative breast cancer.

6. The method of claim 5 , wherein the subject is relapsed or a non-responder to conventional therapy.

7. The method of claim 1 , wherein:
R is C(O)—R 1 ;
R 1 is hydrogen or CH 2 CH 3 ;
R′ is —(CH 2 ) 3 —CH 3 or a phenyl group; and
wherein R 1 and R′ are not the same.

8. The method of claim 7 , wherein the compound is cortexolone 17α-valerate-21-propionate.

9. The method of claim 1 , further comprising administering at least one other chemothereapeutic active ingredient to said subject.

Assignees

• Cosmo Technologies Ltd
• Cosmo Tech Limited

Inventors

• Gerloni Mara

Classifications

• A61P5/46

  for decreasing, blocking or antagonising the activity of glucocorticosteroids · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07J5/0053 Primary

  not substituted in position 16 · CPC title

• A61K31/573 Primary

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title