New aromatase inhibitors from the 3-pyridyl arylether and 1-aryl pyrrolo[2,3-c]pyridine series

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 5, 2012, Pages 1860-1863

  Stauffer, Frédéric ^a   Furet, Pascal ^a   Floersheimer, Andreas ^a   Lang, Marc ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Aromatase; Aromatase inhibition; CYP19

Indexed keywords

1 METHYLPIPERAZINE; 3 CHLOROPHENYLOXY; 3 PYRIDYLOXY; 4 (3 PYRIDAZINYLOXY)BENZONITRILE; 4 (3 PYRIDYLOXY)BENZONITRILE; 4 (3 PYRIDYLOXY)PHTHALONITRILE; 4 (4 PYRIDYLOXY) BENZONITRILE; 4 AMINOCARBONYL; 4 BROMOPHENYL; 4 CHLORO 3 METHYL; 4 CHLOROPHENYL; 4 CYANO 3 METHYL; 4 CYANO 3 PHENOXYPHENYL; 4 CYANOPHENYL; 4 IODOPHENYL; 4 METHOXYPHENYLOXY; AMINOCYCLOHEXYL; AROMATASE INHIBITOR; BENZONITRILE; BENZYLAMINE; CYCLOHEXYLAMINO; LETROZOLE; PHENYLOXY; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; DRUG POTENCY; ENZYME INHIBITION; PHARMACOPHORE; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; AROMATASE; AROMATASE INHIBITORS; BREAST NEOPLASMS; FEMALE; HUMANS; MODELS, MOLECULAR; PYRIDINES; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84857364647     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.01.076     Document Type: Article

References (14)

1. S.E. Bulun, Z. Lin, G. Imir, S. Amin, M. Demura, B. Yilmaz, R. Martin, H. Utsunomiya, S. Thung, B. Gurates, M. Tamura, D. Langoi, and S. Deb Pharmacol. Rev. 57 2005 359
2. Bowman, R.M.; Steele, R.E.; Browne, L. U.S. Patent 4 978 672, 1990.
3. B.P. Haynes, M. Dowsett, W.R. Miller, J.M. Dixon, and A.S. Bhatnagar J. Steroid. Biochem. Mo.l. Biol. 87 2003 35
4. M. Okada, T. Yoden, E. Kawaminami, Y. Shimada, M. Kudoh, and Y. Isomura Chem. Pharm. Bull. 45 1997 482
5. A.L. Hopkins, C.R. Groom, and A. Alex Drug Discovery Today 9 2004 430
6. Buchstaller, H.P.; Wiesner, M.; Schadt, O.; Amendt, C.; Zenke, F.; Sirrenberg, C.; Grell, M.; Finsinger, D. WO 2004037789, 2004.
7. Furet, P.; Batzl, C.; Bhatnagar, A.; Francotte, E.; Rihs, G.; Lang, M. J. Med. Chem. 1993, 36, 1393. The molecules used to construct the model are compounds 4, 7, 8, 11, 12, 13 and 14 of this publication in addition to Letrozole, androstedione, 3-cyclohexyl-3-(4-aminophenyl)piperidine-2,6-dione (an aminoglutethimide derivative) and LY-113174 a pyrimidine inhibitor.
8. D. Ghosh, J. Griswold, M. Erman, and W. Pangborn J. Steroid Biochem. Mol. Biol. 118 2010 197
9. D. Ghosh, J. Griswold, M. Erman, and W. Pangborn Nature 457 2009 219
10. 6, 600 MHz) δ 8.92 (s, 1H), 8.24 (d, 1H), 7.72 (br s, 1H), 7.66 (d, 1H), 7.63 (d, 1H), 7.55 (br d, 1H), 6.79 (d), 2.44 (s, 3H); C NMR δ 139.2, 137.5, 137.0, 133.7, 133.5, 132.1, 132.1, 131.5, 130.1, 126.4, 122.9, 115.4. 103.0, 19.7.
11. Evans, D.; Carley, A.; Stewart, A. et al. WO 2011113798, 2011.
12. Ghosh, D. WO 2009061859, 2009.
13. S. Karkola, H.D. Höltje, and K. Wähälä J. Steroid Biochem. Mol. Biol. 105 2007 63
14. Human CYP19 + P450 reductase SUPERSOMES (#456260, BD Biosciences); fluorometric assay adapted from Stresser, D.M.; Turner S.D.; McNamara, J; Stocker, P.; Miller, V.P.; Crespi, C.L.; Patten, C. J. Anal. Biochem. 2000, 284, 427.