Synthesis and structure-activity relationships of novel benzoxaboroles as a new class of antimalarial agents

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 2, 2011, Pages 644-651

  Zhang, Yong Kang ^a   Plattner, Jacob J ^a   Freund, Yvonne R ^a   Easom, Eric E ^a   Zhou, Yasheen ^a   Gut, Jiri ^b   Rosenthal, Philip J ^b   Waterson, David ^c   Gamo, Francisco Javier ^d   Angulo Barturen, Inigo ^d   Ge, Min ^e   Li, Zhiya ^e   Li, Lingchao ^e   Jian, Yong ^e   Cui, Han ^e   Wang, Hailong ^e   Yang, Jian ^e  

^a PFIZER INC   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c International Center Cointrin   (Switzerland)

^d GLAXOSMITHKLINE   (Spain)

^e Science and Technology Building 24B   (China)

Author keywords

Antimalarial agent; Benzoxaborole; Boron containing compound; Plasmodium falciparum; Structure activity relationship

Indexed keywords

1,3 DIHYDRO 1 HYDROXY 2,1 BENZOXABOROLE; 2 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YLAMINO)ACETIC ACID; 2 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YLOXY)ACETIC ACID; 2 [(1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL) (METHYL)AMINO]ACETIC ACID; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 4 YL) PROPANOIC ACID; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 5 YL) PROPANOIC ACID; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 6 YL) PROPANOIC ACID; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL) 2,2 DIMETHYLPROPANOIC ACID; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL) N,N DIMETHYL PROPANAMIDE; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL)PROPANAMIDE; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL)PROPANENITRILE; 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL)PROPANOIC ACID; 3 (1 HYDROXY 3,3 DIMETHYL 1,3 DIHYDROBENZO[C][1,2] OXABOROL 7 YL)PROPANOIC ACID; 3 (1 HYDROXY 3,4 DIHYDRO 1H BENZO[C][1,2]OXABORININ 8 YL) PROPANOIC ACID; 4 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL)BUTAN 2 ONE; 4 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL)BUTANOIC ACID; 5 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL)PENTANOIC ACID; 7 (2 (1H TETRAZOL 5 YL)ETHYL)BENZO[C][1,2]OXABOROL 1(3H) OL; 7 (3 AMINOPROPYL)BENZO[C][1,2]OXABOROL 1(3H) OL HYDROCHLORIDE SALT; ANTIMALARIAL AGENT; BENZOXABOROLE; METHYL 3 (1 HYDROXY 1,3 DIHYDROBENZO[C][1,2]OXABOROL 7 YL)PROPANOATE; N (CYCLOPROPYLSULFONYL) 3 (1 HYDROXY 1,3 DIHYDROBENZO[C] [1,2]OXABOROL 7 YL) PROPANAMIDE; UNCLASSIFIED DRUG;

ARTICLE; CYTOTOXICITY; DRUG MECHANISM; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; MOLECULAR WEIGHT; NONHUMAN; PLASMODIUM FALCIPARUM;

ANTIMALARIALS; BORON COMPOUNDS; CELL LINE; CELL SURVIVAL; HUMANS; MALARIA, FALCIPARUM; PARASITIC SENSITIVITY TESTS; PLASMODIUM FALCIPARUM; STRUCTURE-ACTIVITY RELATIONSHIP;

PLASMODIUM FALCIPARUM;

EID: 78651277080     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.12.034     Document Type: Article

References (15)

1. M. Enserink Science 328 2010 844
2. S.H.I. Kappe, A.M. Vaughan, J.A. Boddey, and A.F. Cowman Science 328 2010 862
3. M.J. Mackinnon, and K. Marsh Science 328 2010 866
4. M. Enserink Science 328 2010 842
5. M. Rottmann, C. McNamara, B.K. Yeung, M.C. Lee, B. Zou, B. Russell, P. Seitz, D.M. Plouffe, N.V. Dharia, J. Tan, S.B. Cohen, K.R. Spencer, G.E. Gonzalez-Paez, S.B. Lakshminarayana, A. Goh, R. Suwanarusk, T. Jegla, E.K. Schmitt, H.P. Beck, R. Brun, F. Nosten, L. Renia, V. Dartois, T.H. Keller, D.A. Fidock, E.A. Winzeler, and T.T. Diagana Science 329 2010 1175
6. Medicines for Malaria Venture 2009 annual report, www.mmv.org.
7. S.J. Baker, Y.-K. Zhang, T. Akama, A. Lau, H. Zhou, V. Hernandez, W. Mao, M.R.K. Alley, V. Sanders, and J.J. Plattner J. Med. Chem. 49 2006 4447
8. F.L. Rock, W. Mao, A. Yaremchuk, M. Tukalo, T. Crépin, H. Zhou, Y.-K. Zhang, V. Hernandez, T. Akama, S.J. Baker, J.J. Plattner, L. Shapiro, S.A. Martinis, S.J. Benkovic, S. Cusack, and M.R.K. Alley Science 316 2007 1759
9. S.J. Baker, T. Akama, Y.-K. Zhang, V. Sauro, C. Pandit, R. Singh, M. Kully, J. Khan, J.J. Plattner, S.J. Benkovic, V. Lee, and K.R. Maples Bioorg. Med. Chem. Lett. 16 2006 5963
10. Y.-K. Zhang, J.J. Plattner, T. Akama, S.J. Baker, V. Hernandez, V. Sanders, Y. Freund, R. Kimura, W. Bu, K.M. Hold, and X.S. Lu Bioorg. Med. Chem. Lett. 20 2010 2270
11. T. Akama, S.J. Baker, Y.-K. Zhang, V. Hernandez, H. Zhou, V. Sanders, Y. Freund, R. Kimura, K.R. Maples, and J.J. Plattner Bioorg. Med. Chem. Lett. 19 2009 2129
12. D. Ding, Y. Zhao, Q. Meng, D. Xie, B. Nare, D. Chen, C.J. Bacchi, N. Yarlett, Y.-K. Zhang, V. Hernandez, Y. Xia, Y. Freund, M. Abdulla, K.H. Ang, J. Ratnam, J.H. McKerrow, R.T. Jacobs, H. Zhou, and J.J. Plattner ACS Med. Chem. Lett. 1 2010 165
13. 6): δ 12.02 (s, 1H), 8.95 (s, 1H), 7.37 (t, 1H), 7.13-7.22 (m, 2H), 4.96 (s, 2H), 3.00 (t, 2H), 2.54 (t, 2H) ppm. HPLC purity
14. 2 values >0.95.
15. 50's were measured using a 12-point concentration curve, in triplicate and viability was determined using 3-(4,5-dimethylthiazol- 2-yl)-2,5diphenyl-tetrazolium bromide (MTT) after 72 h exposure to compounds.