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Substituted Benzimidazole and Imidazopyridine Compounds Useful as Cyp17 Modulators Patent Highlight Benjamin Blass* Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, Pennsylvania 19140, United States Title: Application Number: Priority Application: Inventors: Assignee Company: Disease Area: Summary:
Substituted Benzimidazole and Imidazopyridine Compounds Useful as Cyp17 Modulators WO 2012044537 Publication Date: April 5, 2012 US 61388837 Priority Date: January 10, 2010 Huang, Audris Bristol Myers Squibb Company, Princeton, New Jersey Cancer Primary Target: Cyp17 Prostate cancer is a leading cause of cancer-related mortality. It has been previously established that androgens such as testosterone and dihydrotestosterone are intimately involved in prostate cancer progression. Androgen synthesis, in turn, is mediated by a series of cytochrome P450 (Cyp) enzymes, including Cyp17, which plays a key role in all androgen synthesis. Cyp17 inhibition would inhibit androgen synthesis and provide a treatment option for prostate cancer patients. This patent application describes a series of substituted benzimidazoles and imidazopyridines and their uses as Cyp17 inhibitors for the treatment of cancer.
Important Compound Classes:
Definitions:
R1 is (i) C1−6 alkyl substituted with 0−4 Ra; (ii) C3−6 cycloalkyl substituted with 0−4 Ra; (iii) −S(O)2(C1−4 alkyl), −S(O)2(C1−4 fluoroalkyl), or −C(O)(C1−6 alkyl); (iv) aryl substituted with 0−6 Rb; (v) heterocyclyl substituted with 0−6 Rc; or (vi) heteroaryl substituted with 0−6 Rc R2 is (i) H, halo, −CN, −ORd, −NReRe, or −C(0)ORf; (ii) C1−6 alkyl substituted with 0−4 Ra; (iii) C3−6 cycloalkyl substituted with 0−4 Ra; (iv) aryl substituted with 0−6 Rb; (v) heterocyclyl substituted with 0−6 Rc; or (vi) heteroaryl substituted with 0−6 Rc
Key Structures:
Recent Review Articles:
Biological Assay
Vasaitis, T. S.; Bruno, R. D.; Njar, V. C. O. Cyp17 inhibitors for prostate cancer therapy. J. Steroid Biochem. Mol. Biol. 2011, 125 (1−2), 23−31. Yap, T. A.; Carden, C. P.; Attard, G.; de Bono, J. S. Targeting Cyp17: Established and novel approaches in prostate cancer. Curr. Opin. Pharmacol. 2008, 8 (4), 449−457. Cyp17 Total SPA Assay employing stably transfected HEK2 cells and 3H-pregnenolone.
Published: July 2, 2012 © 2012 American Chemical Society
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ACS Medicinal Chemistry Letters
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Biological Data
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AUTHOR INFORMATION
Corresponding Author
*Tel: 215-707-1085. E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/ml300157r | ACS Med. Chem. Lett. 2012, 3, 614−615
