Property based optimization of δ-lactam HDAC inhibitors for metabolic stability

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 22, 2010, Pages 6808-6811

  Yoon, Hong Chul ^a   Choi, Eunhyun ^a   Park, Jung Eun ^a   Cho, Misun ^a   Seo, Jeong Jea ^a   Oh, Soo Jin ^b   Kang, Jong Soon ^b   Kim, Hwan Mook ^b   Park, Song Kyu ^b   Lee, Kiho ^b   Han, Gyoonhee ^a  

^a Yonsei University   (South Korea)

^b Korea Research Institute of Bioscience and Biotechnology (KRIBB)   (South Korea)

Author keywords

Histone deacetylase; In vitro ADME; Inhibitor; Lactam; Optimization

Indexed keywords

ATENOLOL; CHLORPROMAZINE; HISTONE DEACETYLASE INHIBITOR; KBH A 118; METOPROLOL; RANITIDINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EXPOSURE; DRUG HALF LIFE; DRUG SCREENING; DRUG STRUCTURE; ENZYME INHIBITION; LIPOPHILICITY; LIVER MICROSOME; MAXIMUM PLASMA CONCENTRATION; METABOLISM; MOUSE; NONHUMAN;

ANIMALS; BIOLOGICAL AVAILABILITY; CELL LINE, TUMOR; HISTONE DEACETYLASE INHIBITORS; HUMANS; LACTAMS; MICE;

ANIMALIA;

EID: 77958052585     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.08.117     Document Type: Article

References (21)

1. S. Spange, T. Wagner, T. Heinzel, and O.H. Kramer Int. J. Biochem. Cell Biol. 41 2009 185
2. J.S. Carew, F.J. Giles, and S.T. Nawrocki Cancer Lett. 269 2008 7
3. J.H. Beumer, and H. Tawbi Curr. Clin. Pharmacol. 2010
4. S. Ropero, and M. Esteller Mol. Oncol. 1 2007 19
5. P. Bertrand Eur. J. Med. Chem. 45 2010 2095
6. P.A. Marks, and R. Breslow Nat. Biotechnol. 25 2007 84
7. C. Campas-Moya Drugs Today (Barc.) 45 2009 787
8. H. Wang, and B.W. Dymock Expert Opin. Ther. Pat. 19 2009 1727
9. H.M. Kim, K. Lee, B.W. Park, D.K. Ryu, K. Kim, C.W. Lee, S.K. Park, J.W. Han, H.Y. Lee, and G. Han Bioorg. Med. Chem. Lett. 16 2006 4068
10. H.M. Kim, D.K. Ryu, Y. Choi, B.W. Park, K. Lee, S.B. Han, C.W. Lee, M.R. Kang, J.S. Kang, S.K. Boovanahalli, S.K. Park, J.W. Han, T.G. Chun, H.Y. Lee, K.Y. Nam, E.H. Choi, and G. Han J. Med. Chem. 50 2007 2737
11. H.M. Kim, S.H. Hong, M.S. Kim, C.W. Lee, J.S. Kang, K. Lee, S.K. Park, J.W. Han, H.Y. Lee, Y. Choi, H.J. Kwon, and G. Han Bioorg. Med. Chem. Lett. 17 2007 6234
12. M.R. Kang, J.S. Kang, S.B. Han, J.H. Kim, D.M. Kim, K. Lee, C.W. Lee, K.H. Lee, C.H. Lee, G. Han, H.M. Kim, and S.K. Park Biochem. Pharmacol. 78 2009 486 and references therein
13. H.M. Kim, S.J. Oh, S.K. Park, G. Han, K. Kim, K.S. Lee, J.S. Kang, M. Nam, and K. Lee Xenobiotica 38 2008 281
14. M.P. Gleeson J. Med. Chem. 51 2008 817
15. N.K. Mukhopadhyay, E. Weisberg, D. Gilchrist, R. Bueno, D.J. Sugarbaker, and M.T. Jaklitsch Ann. Thorac. Surg. 81 2006 1034
16. R. Margueron, A. Licznar, G. Lazennec, F. Vignon, and V. Cavailles J. Endocrinol. 179 2003 41
17. BMDRC, PreADMET 2.0, Bmdrc, Seoul, Korea, 2007.
18. E.H. Kerns, and L. Di Drug Discovery Today 8 2003 316
19. J. Wang, and S. Skolnik Chem. Biodivers. 6 2009 1887
20. D.F. Veber, S.R. Johnson, H.Y. Cheng, B.R. Smith, K.W. Ward, and K.D. Kopple J. Med. Chem. 45 2002 2615
21. 1H NMR (500 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.69 (s, 1H), 7.54 (dd, 1H, JA = 9.5 Hz, JB = 2.0 Hz), 7.40 (dd, 1H, JA = 8.0 Hz, JB = 2.0 Hz), 7.24 (t, 1H, J = 8.0 Hz), 6.38 (br t, 1H, J = 4.0 Hz), 4.53 (s, 2H), 3.31 (d, 2H, J = 7.0 Hz), 2.39 (t, 2H, J = 7.0 Hz), 2.08 (br q, 2H, JA = 7.5 Hz, JB = 6.5 Hz), 2.08 (t, 2H, J = 8.0 Hz).