Substituted Benzimidazole and Imidazopyridine Compounds Useful as Cyp17 Modulators: Patent Highlight

Benjamin Blass

doi:10.1021/ml300157r

editorial

. 2012 Jul 2;3(8):614–615. doi: 10.1021/ml300157r

Substituted Benzimidazole and Imidazopyridine Compounds Useful as Cyp17 Modulators

Patent Highlight

Benjamin Blass ^1,^*

PMCID: PMC4025829 PMID: 24900520

Title:	Substituted Benzimidazole and Imidazopyridine Compounds Useful as Cyp17 Modulators
Application Number:	WO 2012044537	Publication Date:	April 5, 2012
Priority Application:	US 61388837	Priority Date:	January 10, 2010
Inventors:	Huang, Audris
Assignee Company:	Bristol Myers Squibb Company, Princeton, New Jersey
Disease Area:	Cancer	Primary Target:	Cyp17
Summary:	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) C_1–6 alkyl substituted with 0–4 R^a;
	(ii) C_3–6 cycloalkyl substituted with 0–4 R^a;
	(iii) −S(O)₂(C_1–4 alkyl), −S(O)₂(C_1–4 fluoroalkyl), or −C(O)(C_1–6 alkyl);
	(iv) aryl substituted with 0–6 R^b;
	(v) heterocyclyl substituted with 0–6 R^c; or
	(vi) heteroaryl substituted with 0–6 R^c
	R² is
	(i) H, halo, −CN, −OR^d, −NR^eR^e, or −C(0)OR^f;
	(ii) C_1–6 alkyl substituted with 0–4 R^a;
	(iii) C_3–6 cycloalkyl substituted with 0–4 R^a;
	(iv) aryl substituted with 0–6 R^b;
	(v) heterocyclyl substituted with 0–6 R^c; or
	(vi) heteroaryl substituted with 0–6 R^c
Key Structures:
Recent Review Articles:	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.
Biological Assay	Cyp17 Total SPA Assay employing stably transfected HEK2 cells and ³H-pregnenolone.
Biological Data