Steroid-derived cyclopamine analogs and methods for using the same in the prevention or treatment of cancer

• US 8,669,243 B2
• Filed: 06/15/2011
• Issued: 03/11/2014
• Est. Priority Date: 10/30/2007
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: The Wistar Institute, Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Dahmane, Nadia, Winkler, Jeffrey D.
• Primary Examiner(s): Rao, Savitha
• Assistant Examiner(s): Polansky, Gregg
• Application Number:
  US13/160,702
• Publication Number:
  US 20110306662A1
• Time in Patent Office: 1,000 Days
• Field of Search: None
• US Class Current: 514/173
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 493/10 Spiro-condensed systems
• CPC Class Codes: C07J 1/0059 substituted in position 17 by a keto group
• CPC Class Codes: C07J 1/0096 Alkynyl derivatives
• CPC Class Codes: C07J 31/006 not covered by C07J31/003
• CPC Class Codes: C07J 41/0038 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 Class Codes: C07J 41/0072 the A ring of the steroid being aromatic
• CPC Class Codes: C07J 43/003 not condensed
• CPC Class Codes: C07J 69/00 Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by contraction of only one ring by one atom and expansion of only one ring by one atom
• CPC Class Codes: C07J 71/001 Oxiranes
• CPC Class Codes: C07J 75/005 Preparation of steroids by cyclization of non-steroid compounds

Abstract

The present invention relates to steroid-derived cyclopamine analogs and methods for using the same for inhibiting sonic hedgehog signaling and preventing or treating cancer. A method for synthesizing the analogs of the present invention from a steroid is also provided.

Claims

1. A steroid-derived cyclopamine analog that inhibits sonic hedgehog signaling, wherein said analog has the structure:

2. A pharmaceutical composition comprising a steroid-derived cyclopamine analog of claim 1 in admixture with a pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2, wherein said composition is formulated for parenteral, transdermal, oral, subcutaneous, intrapulmonary, topical or intranasal administration.

4. A method for inhibiting sonic hedgehog signaling in a cell comprising contacting a cell with steroid-derived cyclopamine analog of claim 1 thereby inhibiting sonic hedgehog signaling in the cell.

5. The method of claim 4, wherein said method is carried out in vitro.

6. The method of claim 4, wherein the cell is a cancer cell.