Abstract
A number of substituted isoquinolin-1-ones, possible bioisosteres of the 5-aryl substituted 2,3-dihydroimidaz[2,1-a]isoquinolines, were synthesized and tested for their antitumor activity against five different human tumor cell lines.O-(3-hydroxypropyl) substituted compound (15) exhibited the best antitumor activity which is 3–5 times better than 5-[4′-(piperidinomethyl) phenyl]-2,3-dihydroimidazo[2,1-a]isoquinoline (1).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References Cited
Berdel, W. E. and Munder, P. G., Antitumor Analogs of PAF, In Snyder, F. (Ed.)Platelet-Activating Factor and Related Lipid Mediators. Plenum Press, New York, pp. 449–467, 1987.
Brunton, V. G., Workman, P., Br.J. Cancer, 67, 989 (1993).
Cheon, S. H., Park, J. S., Jeong, S. H., Chung, B. H., Choi, B. G., Cho, W. J., Kang, B. H., Lee, C. O., Synthesis and Structure-Activity Relationship Studies of 2,3-Dihydroimidazo[2,1-a]isoquinoline Analogs as Antitumor Agents.Arch. Pharm. Res., 20, 138–143 (1997).
Cho, W. J., Yoo, S. J., Chung, B. H., Choi, B. G., Cheon, S. H., Whang, S. H., Kim, S. K., Kang, B. H., Lee, C. O., Synthesis of Benzol[c]phenanthridine Derivatives and theirin vitro Antitumor Activities.Arch. Pharm. Res., 19, 321–325 (1996).
Danhauser-Riedl, S., Felix, S. B., Houlihan, W. J., Zafferani, M., Steinhauser, G., Oberberg, D., Kalvelage, H., Busch, R., Rastetter, J., Berdel, W. F.,Cancer Res., 51, 43 (1991).
Dive, C., Watson, J. V. and Workman, P., Multiparametric Flow Cytometry of the Modulation of Tumor Cell Membrane Permeability by Developmental Antitumor Ether Lipid SRI 62–834 in EMT6 Mouse Mammary Tumor and HL60 Human Promyelocytic Leukemia cells.Cancer Res., 51, 799–806 (1990).
Houlihan, W. J. and Parrino, V. A., Directed Lithiation of 2-Phenyl- and 2-(o-methylphenyl)imidazoline.J. Org. Chem., 47, 5177–5180 (1982).
Houlihan, W. J., Cheon, S. H., Parrino, V. A., Handley, D. A. and Larson, D. A., Structural Modification of 5-Aryl-2,3-dihydroimidazo[2,1-a]isoquinoline Platelet Activating Factor Receptor Antagonists.J. Med. Chem., 36, 3098–3102 (1993).
Houlihan, W. J., Munder, P. G., Handley, D. A., Cheon, S. H. and Parrino, V. A., Antitumor Activity of 5-Aryl-2,3-dihydroimidazo[2,1-a]isoquinolines.J. Med. Chem., 38, 234–240 (1995a).
Houlihan, W. J., Munder, P. G., Handley, D. A. and Nemecek, G. A., Priclinical Pharmacology and Possible Mechanism of Action of the Novel Antitumor Agent 5-(4′-Piperidinomethylphenyl)-2,3-dihydromidazo[2,1-a]isoquinoline.Arzneim.-Forsch./Drug Res., 45(II), 1133–1137 (1995c).
Modest, E. J., Berens, M. E., Piantadosi, C. and Noseda, A., Pharmacological Effects and Anticancer Activity of New Ether Phospholipid Analogs, In Kabara J. J. (Ed).The Pharm. acological Effect of lipids III, Role of Lipids in Cancer Research. The American Oil Chemists' Society, Champaign, IL, pp. 330–337, 1989.
Munder, P. G. and Westphal, O., Antitumoral and Other Biomedical Activities of Synthetic Ether Lysophospholipids, In Waksman, B. H. (Ed). 1939–1989:Fifty Years Progress in Allergy Karger, New York, pp. 206–235, 1990.
Noseda, A., Godwin, P. L. and Modest, E. J., Effects of Antineoplastic Ether Lipids on Model and Biological Membranes.Biochim. Biophys. Acta, 945, 92–100 (1988).
Poindexter, G. S.,J. Org. Chem., 47, 3787–3788 (1982).
Rubinstein, L. V., Shoemaker, R. H., Paul, K. D., Simon, R. M., Tosini, S., Skehan, P., Scudiero, D., Monks, A. and Boyd, M. R.J. Natl. Cancer Inst., 82, 1113 (1990).
Seewald, M. J., Olsen, R. A., Sehgal, I., Melder, D. C., Modest, E. J. and Powis, G., Inhibition of Growth Factor-Dependent Inositol Phosphate Ca2+ Signaling by Antitumor Ether Lipid Analogues.Cancer Res., 50, 4458–4463 (1990).
Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J. B., Vistica, D. T., Warren, J. T., Bokesch, H., Kenny, S. and Boyd, M. R.,J. Natl. Cancer Inst., 82, 1107 (1990).
Still, W. C., Kahn, M., Mitra, A. J.,J. Org. Chem., 43, 2923 (1978).
Uberall, F., Oberhuber, H., Maly, K., Zaknun, J., Demuth, L. and Grunicke, H. H., Hexadecylphosphocholine Inhibits Inositol Phosphate Formation and Protein Kinase C Activity.Cancer Res., 51, 807–812 (1991).
Workman, P., Antitumor Ether Lipids: Endocytosis as a Determination of Cellular Sensitivity.Cancer Cells, 3, 315–317 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cheon, S.H., Park, J.S., Chung, BH. et al. Synthesis and structure-activity relationship studies of substituted isoquinoline analogs as antitumor agent. Arch. Pharm. Res. 21, 193–197 (1998). https://doi.org/10.1007/BF02974027
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02974027