Anti-cancer agents and androgen inhibition activity compound

• US 7,960,435 B2
• Filed: 12/14/2007
• Issued: 06/14/2011
• Est. Priority Date: 12/15/2006
• Status: Active Grant

• Current Assignee: University of Maryland Baltimore County (University of Maryland)
• Original Assignee: University of Maryland Baltimore County (University of Maryland)
• Inventors: Njar, Vincent C. O., Purushottamachar, Puranik
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US12/519,233
• Publication Number:
  US 20100113600A1
• Time in Patent Office: 1,278 Days
• Field of Search: 514/604
• US Class Current: 514/604
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61P 5/26 Androgens

Abstract

A qualitative 3D pharmacophore model (a common feature based model or Catalyst HipHop algorithm) developed from well-known natural product androgen receptor down-regulating agents (ARDAs). The 3D pharmacophore model is used as a template in virtual screening compounds for new ARDAs. ARDA compounds and compounds that strongly inhibit the growth of human prostate LNCaP cells. The compounds may be used in compositions and methods of inhibiting cell proliferation of a cancer and methods of preventing or treating cancer, including prostate cancer.

Claims

1. A method for inhibiting androgen activity in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising

an androgen inhibition activity compound of structure (1);

and

a pharmaceutically acceptable carrier, diluent or excipient,

3. The method of claim 1, wherein

W is selected from the group consisting of H, cyano, —

NO₂, —

COOH and 1H-tetrazole;

X is selected from H, methyl and F,

Y is selected from H, methyl and F,

Z is selected from H and methyl,

and

R is selected from H and methyl.

4. The method of claim 1, wherein said androgen inhibition activity compound is a compound of formula BTB01434 or 6-18:

5. The method of claim 1, wherein said androgen inhibition activity comprises activity selected from the group consisting of decreasing androgen synthesis or concentration, AR downregulation and/or AR modulation, and preventing the binding of an androgen to an androgen receptor or competing with an androgen and its binding to an androgen receptor.

6. The method of claim 1, wherein said androgen inhibition activity compound comprises a marker.

7. The method of claim 6, wherein said marker allows identification when the compound is bound with a cancer cell.

2. A method for inhibiting androgen activity in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising an androgen inhibition activity compound is selected from the group consisting of [(4-Methylphenyl)sulfonyl](2-nitrophenyl)amine, (2-Nitrophenyl)(phenylsulfonyl)amine, (4-Methyl-2-nitrophenyl)(phenylsulfonyl)amine, [(4-Fluorophenyl)sulfonyl](4-methyl-2-nitrophenyl)amine, 5-Methyl-2-[(phenylsulfonyl)amino]benzoic acid, and [(4-Methylphenyl)[(4-methylphenyl)sulfonyl]amine.