Cyclopamine analogs

Patent metadata

Field	Value
Publication number	US-9492435-B2
Application number	US-201414203297-A
Country	US
Kind code	B2
Filing date	Mar 10, 2014
Priority date	Dec 28, 2006
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

The invention provides derivatives of cyclopamine having the following formula:

First claim

The invention claimed is:

1. A compound having the structure:

where R is selected from the group consisting of —H, —OH, and a nitrogen protecting group,
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R is —OH.

3. The compound of claim 1 , wherein R is a nitrogen protecting group selected from the group consisting of formyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, phenyl acetyl, benzoyl, benzamide, alkyl carbamate, aralkyl carbamate, aryl carbamate, allyl, aralkyl, alkoxymethyl, aralkoxymethyl, N-2-cyanoethyl, diarylphosphinamide, dialkylphosphinamidate, diarylphosphinamidate, and trialkylsilyl.

4. The compound of claim 3 , where the nitrogen protecting group is benzyl carbamate,

or benzoyl,

5. The compound of claim 1 , wherein R is H, and the compound is in the form of a pharmaceutically acceptable quaternary ammonium salt.

6. The compound of claim 5 , wherein the pharmaceutically acceptable salt is an inorganic acid addition salt.

7. The compound of claim 6 , where the inorganic acid addition salt is a hydrochloride salt.

8. A crystalline form of the compound of claim 7 .

9. A pharmaceutical composition comprising a compound having the structure:

where R is selected from the group consisting of —H, —OH, and a nitrogen protecting group, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

10. The composition of claim 9 , wherein R is —OH.

11. The composition of claim 9 , wherein R is H, and the compound is in the form of a pharmaceutically acceptable quaternary ammonium salt.

12. The composition of claim 11 , wherein the pharmaceutically acceptable salt is an inorganic acid addition salt.

13. The composition of claim 12 , where the inorganic acid addition salt is a hydrochloride salt.

14. The composition of claim 13 , wherein the composition is in liquid form.

15. The composition of claim 9 , in a form suitable for topical application.

Assignees

• Infinity Pharmaceuticals Inc

Inventors

• Austad Brian
• Behnke Mark L
• Castro Alfredo C
• Grogan Michael J
• Janardanannair Somarajannair
• Lescarbeau Andre
• Peluso Stephane
• Charette Andre B
• Tremblay Martin R

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D307/94

  spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins · CPC title