Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents

Journal of Medicinal Chemistry

Volumn 54, Issue 8, 2011, Pages 3076-3080

  Tung, Yen Shih ^a,b   Coumar, Mohane Selvaraj ^c   Wu, Yu Shan ^d   Shiao, Hui Yi ^a   Chang, Jang Yang ^a   Liou, Jing Ping ^e   Shukla, Paritosh ^a   Chang, Chun Wei ^a   Chang, Chi Yen ^a   Kuo, Ching Chuan ^a   Yeh, Teng Kuang ^a   Lin, Chin Yu ^a   Wu, Jian Sung ^a   Wu, Su Ying ^a   Liao, Chun Chen ^b,f   Hsieh, Hsing Pang ^a  

^a NATIONAL HEALTH RESEARCH INSTITUTES   (Taiwan)

^b NATIONAL TSING HUA UNIVERSITY   (Taiwan)

^c PONDICHERRY UNIVERSITY   (India)

^d TUNGHAI UNIVERSITY   (Taiwan)

^e TAIPEI MEDICAL UNIVERSITY   (Taiwan)

^f CHUNG YUAN CHRISTIAN UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

(6 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)(3,4,5 TRIMETHOXYPHENYL)METHANONE; 7 AZAINDOLE DERIVATIVE; ANTINEOPLASTIC AGENT; AROMATIC COMPOUND; BICYCLO COMPOUND; BPR 0L075; MOLECULAR SCAFFOLD; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG STABILITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANTINEOPLASTIC AGENTS; BICYCLO COMPOUNDS; BIOLOGICAL AVAILABILITY; CELL LINE, TUMOR; HUMANS;

EID: 79955424472     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm101027s     Document Type: Article

References (14)

1. Ciapetti, P. and Giethlen, B. Molecular Variations Based on Isosteric Replacements. In The Practice of Medicinal Chemistry, 3 rd ed.; Wermuth, C. G., Ed.; Academic Press: Boston, MA, 2008; pp 290 - 342.
2. Liou, J. P.; Chang, Y. L.; Kuo, F. M.; Chang, C. W.; Tseng, H. Y.; Wang, C. C.; Yang, Y. N.; Chang, J. Y.; Lee, S. J.; Hsieh, H. P. Concise synthesis and structure-activity relationships of combretastatin A-4 analogues, 1-aroylindoles and 3-aroylindoles, as novel classes of potent antitubulin agents J. Med. Chem. 2004, 47, 4247-4257
3. Hagishita, S.; Yamada, M.; Shirahase, K.; Okada, T.; Murakami, Y.; Ito, Y.; Matsuura, T.; Wada, M.; Kato, T.; Ueno, M.; Chikazawa, Y.; Yamada, K.; Ono, T.; Teshirogi, I.; Ohtani, M. Potent inhibitors of secretory phospholipase A2: synthesis and inhibitory activities of indolizine and indene derivatives J. Med. Chem. 1996, 39, 3636-3658 (Pubitemid 26307871)
4. Hatanaka, M.; Takahashi, K.; Nakamura, S.; Mashino, T. Preparation and antioxidant activity of alpha-pyridoin and its derivatives Bioorg. Med. Chem. 2005, 13, 6763-6770 (Pubitemid 41571221)
5. Lukin, K.; Hsu, M. C.; Fernando, D.; Leanna, M. R. New practical synthesis of indazoles via condensation of o -fluorobenzaldehydes and their O -methyloximes with hydrazine J. Org. Chem. 2006, 71, 8166-8172 (Pubitemid 44571824)
6. Duan, J. X.; Cai, X.; Meng, F.; Lan, L.; Hart, C.; Matteucci, M. Potent antitubulin tumor cell cytotoxins based on 3-aroyl indazoles J. Med. Chem. 2007, 50, 1001-1006 (Pubitemid 46394002)
7. Sundberg, R. J.; Songchun, J. Improved procedures for preparation of 4-hydroxy- and 2-amino-4-methoxypyridines Org. Prep. Proced. Int. 1997, 29, 117-122
8. Ohshiro, Y.; Komatsu, M.; Minakata, S. Regioselective functionalization of 1 H -pyrrolo[2,3- b ]pyridine via its N -oxide Synthesis 1992, 1992, 661-663
9. Wang, T.; Wallace, O. B.; Zhang, Z.; Meanwell, N. A.; Bender, J. A. Antiviral Azaindole Derivatives. WO0162255A1, 2001.
10. Seela, F.; Chen, Y.; Bindig, U.; Kazimierczuk, Z. Synthesis of 2′-deoxyisoinosine and related 2′-deoxyribonucleosides Helv. Chim. Acta 1994, 77, 194-202
11. Tavares, F. X.; Boucheron, J. A.; Dickerson, S. H.; Griffin, R. J.; Preugschat, F.; Thomson, S. A.; Wang, T. Y.; Zhou, H. Q. N -Phenyl-4-pyrazolo[1, 5- b ]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy J. Med. Chem. 2004, 47, 4716-4730 (Pubitemid 39195562)
12. Wu, Y. S.; Coumar, M. S.; Chang, J. Y.; Sun, H. Y.; Kuo, F. M.; Kuo, C. C.; Chen, Y. J.; Chang, C. Y.; Hsiao, C. L.; Liou, J. P.; Chen, C. P.; Yao, H. T.; Chiang, Y. K.; Tan, U. K.; Chen, C. T.; Chu, C. Y.; Wu, S. Y.; Yeh, T. K.; Lin, C. Y.; Hsieh, H. P. Synthesis and evaluation of 3-aroylindoles as anticancer agents: metabolite approach J. Med. Chem. 2009, 52, 4941-4945
13. Liou, J. P.; Mahindroo, N.; Chang, C. W.; Guo, F. M.; Lee, S. W.; Tan, U. K.; Yeh, T. K.; Kuo, C. C.; Chang, Y. W.; Lu, P. H.; Tung, Y. S.; Lin, K. T.; Chang, J. Y.; Hsieh, H. P. Structure-activity relationship studies of 3-aroylindoles as potent antimitotic agents ChemMedChem 2006, 1, 1106-1118 (Pubitemid 44622251)
14. Hsieh, H.-P.; Chao, Y.-S.; Liou, J.-P.; Chang, J.-Y.; Tung, Y.-S. Anti-Tumor Compounds. US7456289, 2008.