Synthesis and in vitro antitumor activity of 1-(3-dimethylamino)propyl indolin-2-one derivatives

Medicinal Chemistry Research

Volumn 22, Issue 4, 2013, Pages 1723-1729

  Lv, Kai ^a,b   Wang, Li Li ^a   Zhou, Xin Bo ^a   Liu, Ming Liang ^b   Liu, Hong Ying ^a   Zheng, Zhi Bing ^a   Li, Song ^a  

^a BEIJING INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY   (China)

^b INSTITUTE OF MEDICINAL BIOTECHNOLOGY   (China)

Author keywords

Antitumor activity; Indolin 2 ones; Synthesis; VEGF

Indexed keywords

1 (3 DIMETHYLAMINO)PROPYL INDOLIN 2 ONE DERIVATIVE; 1 [3 (DIMETHYLAMINO)PROPYL] 3 (DIPHENYLMETHYLENE) 5 FLUOROINDOLIN 2 ONE HYDROCHLORIDE; 1 [3 (DIMETHYLAMINO)PROPYL] 5 FLUORO 3 [PHENYL(1H PYRROL 2 YL)METHYLENE]INDOLIN 2 ONE HYDROCHLORIDE; 3 [1 (1H PYRROL 2 YL)ETHYLIDENE] 1 [3 (DIMETHYLAMINO)PROPYL] 5 FLUOROINDOLIN 2 ONE HYDROCHLORIDE; 3 [1 (1H PYRROL 2 YL)PROPYLIDENE] 1 [3 (DIMETHYLAMINO)PROPYL] 5 FLUOROINDOLIN 2 ONE HYDROCHLORIDE; 3 [[3,5 DIMETHYL 4 (MORPHOLINE 4 CARBONYL) 1H PYRROL 2 YL]METHYLENE] 1 [3 (DIMETHYLAMINO)PROPYL] 5 FLUOROINDOLIN 2 ONE HYDROCHLORIDE; 5 CHLORO 3 [[3,5 DIMETHYL 4 (MORPHOLINE 4 CARBONYL) 1H PYRROL 2 YL]METHYLENE] 1 [3 (DIMETHYLAMINO)PROPYL]INDOLIN 2 ONE HYDROCHLORIDE; ANTINEOPLASTIC AGENT; BASIC FIBROBLAST GROWTH FACTOR RECEPTOR; ETHYL 5 [[1 [3 (DIMETHYLAMINO)PROPYL] 5 FLUORO 2 OXOINDOLIN 3 YLIDENE]METHYL] 2,4 DIMETHYL 1H PYRROLE 3 CARBOXYLATE HYDROCHLORIDE; ETHYL 5 [[5 CHLORO 1 [3 (DIMETHYLAMINO)PROPYL] 2 OXOINDOLIN 3 YLIDENE]METHYL] 2,4 DIMETHYL 1H PYRROLE 3 CARBOXYLATE HYDROCHLORIDE; INDOLE DERIVATIVE; SEMAXANIB; SUNITINIB; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; STRUCTURE ACTIVITY RELATION;

EID: 84879693816     PISSN: 10542523     EISSN: 15548120     Source Type: Journal    
DOI: 10.1007/s00044-012-0170-3     Document Type: Article

References (19)

1. David SS (1993) Preparation of oxindole. J Chem Educ 70:332
2. Gayido DA, Buldain G, Frydman B (1984) 1,4-Diaminoalkanes from pyrroles. A new synthetic approach to substituted putrescines. J Org Chem 49:2619-2622
3. Green LM, Reade JL, Ware CF (1984) Rapid colorimetric assay for cell viability: application to the quantitation of cytotoxic and growth inhibitory lymphokines. J Immunol Methods 70:257-268
4. Ikezoe T, Nishioka C, Tasaka T, Yang Y, Komatsu N, Togitani K, Koeffler HP, Taguchi H (2006) The antitumor effects of sunitinib (formerly SU11248) against a variety of human hematologic malignancies: enhancement of growth inhibition via inhibition of mammalian target of rapamycin signaling. Mol Cancer Ther 5:2522-2530
5. Islam I, Bryant J, Chou YL, Kochanny MJ, Lee W, Phillips GB, Yu H, Adler M, Whitlow M, Ho E, Lentz D, Polokoff MA, Subramanyam B, Wu JM, Zhu D, Feldman RI, Arnaiz DO (2007a) Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett 17:3814-3818
6. Islam I, Brown G, Bryant J, Hrvatin P, Kochanny MJ, Phillips GB, Yuan S, Adler M, Whitlow M, Lentz D, Polokoff MA, Wu J, Shen J, Walters J, Ho E, Subramanyam B, Zhu D, Feldman RI, Arnaiz DO (2007b) Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517. Bioorg Med Chem Lett 17:3819-3925
7. Kammasud N, Boonyarat C, Sanphanya K, Utsintong M, Tsunoda S, Sakurai H, Saiki I, Andre I, Grierson DS, Vajragupta O (2009) 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases. Bioorg Med Chem Lett 19:745-750
8. Lai Y, Ma L, Huang WX, Yu X, Zhang YH, Ji H, Tian J (2010) Synthesis and biological evaluation of 3-[4-(amino/methylsulfonyl)phenyl]methylene-indolin-2- one derivatives as novel COX-1/2 and 5-LOX inhibitors. Bioorg Med Chem Lett 20:7349-7353
9. Lu HY, Lin C, Li S, Zheng ZB, Zhang XY, Zhang LS, Xu GZ, Guo SX, Fu M, Wu M (2003) Antitumor activity of an indolin-2-ketone compound Z24 in vivo and its anti-angiogenesis activity. Chin J Pharmacol Toxicol 17:401-407
10. Lu HY, Lin C, Zheng ZB, Li S, Guo SX, Zhang X, Fu M, Liang X, Wu M (2005) Angiogenesis inhibitor Z24 induces endothelial cell apoptosis and suppresses tumor growth and metastasis. J Pharmacol Sci 97:533-540
11. Lv K, Feng LS, Liu ML, Guo HY (2010) Advances of quinolones as potent antitumor agents and the structure-activity relationships. Chin J Pharm 41:456-463
12. Lv K, Wang LL, Liu ML, Zhou XB, Fan SY, Liu HY, Zheng ZB, Li S (2011) Synthesis and antitumor activity of 5-[1-(3-(dimethylamino)propyl)-5- halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3- carboxamides. Bioorg Med Chem Lett 21:3062-3065
13. Lyros O, Mueller A, Heidel F, Schimanski CC, Gockel I, Galle PR, Lang H, Moehler M (2010) Analysis of anti-proliferative and chemosensitizing effects of sunitinib on human esophagogastric cancer cells: synergistic interaction with vandetanib via inhibition of multi-receptor tyrosine kinase pathways. Int J Cancer 127:1197-1208
14. Morabito A, Maio ED, Maio MD, Normanno N, Perrone F (2006) Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist 11:753-764
15. Shaheen RM, Davis DW, Liu WB, Zebrowski BK, Wilson MR, Bucana CD, McConkey DJ, McMahon G, Ellis LM (1999) Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res 59:5412-5416
16. Sun L, Liang C, Shirazian S, Zhou Y, Miller T, Cui J, Fukuda JY, Chu JY, Nematalla A, Wang XY, Chen H, Sistla A, Luu TC, Tang F, Wei J, Tang C (2003) Discovery of 5-[5-fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid(2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem 46:1116-1119
17. Wallace DM, Leung SH, Senge M, Smith KM (1993) Rational tetraarylporphyrin syntheses: tetraarylporphyrins from the Macdonald route. J Org Chem 58:7245-7257
18. Wang LL, Li JJ, Zheng ZB, Liu HY, Du GJ, Li S (2004) Antitumor activities of a novel indolin-2-ketone compound, Z24: more potent inhibition on bFGF-induced angiogenesis and bcl-2 over-expressing cancer cells. Eur J Pharmacol 502:1-10
19. Young E, Miele L, Tucker KB, Huang M, Wells J, Gu JW (2010) SU11248, a selective tyrosine kinases inhibitor suppresses breast tumor angiogenesis and growth via targeting both tumor vasculature and breast cancer cells. Cancer Biol Ther 10:703-711