Inhibitors of 17β-HSD1, 17β-HSD3 and 17β-HSD10

Patent metadata

Field	Value
Publication number	US-11072632-B2
Application number	US-201214007577-A
Country	US
Kind code	B2
Filing date	Mar 26, 2012
Priority date	Mar 25, 2011
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSD1 inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSD1 and 17β HSD3 that have a spiro-morpholine substituent at C20.

First claim

What is claimed is:

1. An inhibitor of 17β-HSD1, wherein the inhibitor is of the structure:

wherein R is halo, —NH 2 , alkyl, —OCH 2 CH 2 Br, aralkyl, carboxy, —CH 2 -heterocyclyl, heterocyclyloyl, —C(O)N(R′)(R″) or —B(OH) 2 ,
wherein R′ and R″ are independently or simultaneously H or alkyl, or R′ and R″ are joined together, along with the nitrogen atom to which they are attached, to form a heterocyclic ring,

or a pharmaceutically acceptable salt or tautomer thereof.

2. The inhibitor of claim 1 , wherein the inhibitor is of the structure

or a pharmaceutically acceptable salt thereof.

3. The inhibitor of claim 2 , wherein the inhibitor is of the structure

4. An inhibitor of 17β-HSD1, wherein the inhibitor is of the structure:

or a pharmaceutically acceptable salt thereof.

5. A radiolabeled compound of the structure

wherein X is I 123 , I 125 , I 131 or Br 76 , or a pharmaceutically acceptable salt or tautomer thereof.

6. A method of treating breast cancer or prostate cancer in a subject comprising administering to said subject a radiolabeled compound of claim 5 .

Assignees

• Poirier Donald
• Roy Jenny
• Maltais Rene
• Univ Laval

Inventors

• Poirier Donald
• Roy Jenny
• Maltais Rene

Classifications

• C12Y101/01051

  3 (or 17)-Beta-hydroxysteroid dehydrogenase (1.1.1.51) · CPC title

• C07J1/0007

  not substituted in position 17 · CPC title

• C07J41/0011

  Unsubstituted amino radicals · CPC title

• C07J41/0038

  with an androstane skeleton, including 18- or 19-substituted derivatives, 18-nor derivatives and also derivatives where position 17-beta is substituted by a carbon atom not directly bonded to a further carbon atom and not being part of an amide group · CPC title

• C07J21/00

  Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton · CPC title