Citation: Ying Meng, Guan Wang, Yue Li, Kuan Hou, Yue Yuan, Li-Juan Zhang, Hong-Rui Song, Wei Shi. Synthesis and biological evaluation of new pyrrolopyrazinone compounds as potential antitumor agents[J]. Chinese Chemical Letters, ;2013, 24(07): 619-621. shu

Synthesis and biological evaluation of new pyrrolopyrazinone compounds as potential antitumor agents

Ying Meng ^a ,
Guan Wang ^b ,
Yue Li ^a ,
Kuan Hou ^a ,
Yue Yuan ^a ,
Li-Juan Zhang ^a ,
Hong-Rui Song ^a,, ,
Wei Shi ^b,,

1.
a Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;
2.
b Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Changchun 130012, China

Corresponding author: Hong-Rui Song, Wei Shi,
Received Date: 6 March 2013
Available Online: 28 March 2013

A series of pyrrolo[1,2-a]pyrazinone compounds (5a-9f) were synthesized, and their cytotoxic activity against SKOV-3, A549, HeLa cells in vitro were evaluated by the MTT method. Some of the compounds showed potential antitumor activity against three tumor cell lines. Among them, compounds 9c and 9d showed the most potent cytotoxic activity. The preliminary mechanism of action was discussed.
- Pyrrolopyrazinone,
- Antitumor,
- Synthesis
1. [1]
  [1] F. Deng, J.J. Lu, H.Y. Liu, Synthesis and antitumor activity of novel salvicine analogues, Chin. Chem. Lett. 22 (2011) 25-28.
2. [2]
  [2] E.N. Delphine, M. Peter, L. Thomas, Chiroptical analysis of marine sponge alkaloids sharing the pyrrolopyrazinone core, Chem. Eur. J. 10 (2004) 1141-1148.
3. [3]
  [3] A. Umeyama, S. Ito, E. Yuasa, et al., A new bromopyrrole alkaloid and the optical resolution of the racemate from the marine sponge Homaxinella sp., J. Nat. Prod. 61 (1998) 1433-1434.
4. [4]
  [4] G.B. Martin, M.B. Andrew, C.W. Anthony, First syntheses of the pyrroloketopiperazine marine natural products (±)-longamide, (±)-longamide B, (±)-longamide B methyl ester and (±)-hanishin, New J. Chem. 23 (1999) 687-690.
5. [5]
  [5] R.B. Kinnel, H.P. Gehrken, R. Swali, Palau'amine and its congeners: a family of bioactive bisguanidines from the marine sponge Stylotella aurantium 1, J. Org. Chem. 63 (1998) 3281-3286.
6. [6]
  [6] L. Thomas, J.E.N. Delphine, Z. Michael, Study on the absolute configuration of ()-palau'amine, Tetrahedron Lett. 51 (2010) 6353-6355.
7. [7]
  [7] Data for new compounds. 5a: Yield 62%. Mp: 147-150℃; ESI-MS: m/z 163.9[M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 6.95 (s, 1H), 6.63 (d, 1H), 6.19-6.12 (m, 1H), 4.83 (s, 1H), 4.67 (s, 2H), 1.13 (s, 3H). 5b: Yield 67%. Mp: 153-155℃; ESI-MS: m/z 192.2 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 6.99-6.93 (m, 1H), 6.60 (dd, 1H), 6.13 (dd, 1H), 4.24 (d, 1H), 3.89 (d, 1H), 3.51 (dt, 1H), 3.36-3.24 (m, 2H), 3.13 (m, 2H), 1.17 (s, 3H). 6a: Yield 31%. Mp: 144-146℃; ESI-MS: m/z 205.9 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.32 (dd, 1H), 7.24 (s, 1H), 6.83-6.80 (m, 1H), 6.50 (dd, 1H), 5.37 (s, 1H), 2.20 (s, 3H), 1.13 (s, 3H). 6b: Yield 27%. Mp: 182-185℃; ESIMS: m/z 234.2 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.33 (m, 1H), 7.25 (dd, 1H), 6.84 (dd, 1H), 6.50 (s, 1H), 4.06 (m, 2H), 3.50 (m, 2H), 2.24 (s, 3H), 1.23 (s, 3H). 6c: Yield 36%. Mp: 176-178℃; ESI-MS: m/z 261.9 [M+Na]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.33 (dd, 1H), 7.24 (s, 1H), 6.84-6.79 (m, 1H), 6.50 (dd, 1H), 5.39 (s, 2H), 2.21 (s, 3H). 6d: Yield 34%. Mp: 200-202℃; ESI-MS: m/z 267.9 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.11-7.05 (m, 1H), 6.66 (dd, 1H), 6.14 (dd, 1H), 4.94 (d, 1H), 4.94 (d, 1H), 4.51-4.29 (m, 1H), 4.07 (dt, 1H), 3.99 (d, 1H), 3.95-3.78 (m, 1H), 3.73 (dd, 1H), 3.45 (dt, 1H), 1.40 (s, 3H). 8a: Yield 73%. Mp: 139-141℃; ESIMS: m/z 240 [M]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.44 (d, J=8.2 Hz, 1H), 7.09 (s, 1H), 7.03 (d, J=8.2 Hz, 2H), 6.66 (d, 1H), 6.55 (s, 1H), 5.93-5.88 (m, 1H), 5.50 (s, 2H), 2.20 (s, 3H). 8b: Yield 78%. Mp: 191-193℃; ESI-MS: m/z 268 [M]⁺, ¹H NMR (300 MHz, DMSO-d₆): δ 7.11 (d, 2H, J=8.2 Hz), 7.03 (d, 2H, J=8.2 Hz), 6.72-6.67 (m, 1H), 6.56 (dd, 1H), 5.97 (dd, 1H), 4.55 (d, 1H), 4.30 (t, 1H), 4.23 (d, 1H), 3.54 (dt, 1H), 3.47-3.35 (m, 1H), 2.18 (s, 3H), 1.02 (t, 2H). 9a: Yield 29%. Mp: 111-112℃; ESI-MS: m/z 282 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 10.52 (s, 1H), 7.45 (dd, 1H), 7.37 (s, 1H), 7.27 (d, 2H, J=8.1 Hz), 7.19 (d, 2H, J=8.1 Hz), 6.96 (d, 1H, J=3.9 Hz), 6.57 (dd, 1H, J=3.9, 2.6 Hz), 2.31 (s, 3H), 1.71 (s, 3H). 9b: Yield 31%. Mp: 194-197℃; ESI-MS: m/z 310 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.18 (d, 2H, J=8.3 Hz), 7.13-7.09 (m, 1H), 7.06 (d, 2H, J=8.3 Hz), 6.60 (dd, 1H), 6.09 (dd, 1H), 5.62 (d, 1H, J=13.0 Hz), 4.34 (d, 1H, J=13.0 Hz), 4.22-4.10 (m, 1H), 3.94 (dd, 1H), 3.88-3.77 (m, 1H), 3.62 (dt, 1H), 2.21 (s, 3H), 2.04 (s, 3H). 9c: Yield 23%. Mp: 110-113℃; ESI-MS: m/z 316 [M+H]⁺; ¹H NMR(300 MHz, DMSO-d₆): δ 7.90 (d, 2H, J=8.2 Hz), 7.35 (d, 2H, J=8.2 Hz), 7.13-7.08 (m, 1H), 6.87 (dd, 1H), 6.14 (dd, 1H), 5.81 (s, 2H), 3.57 (s, 2H), 2.37 (s, 3H). 9d: Yield 23%. Mp: 191-193℃; ESI-MS: m/z 343.9 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 7.15 (d, 2H, J=8.3 Hz), 7.12-7.09 (m, 1H), 7.05 (d, 2H, J=8.3 Hz), 6.59 (dd, 1H), 6.07 (dd, 1H), 5.60 (d, 1H), 4.40 (dt, 3H), 4.16 (dt, 1H), 4.03-3.80 (m, 2H), 3.62 (dt, 1H), 2.18 (s, 3H). 9e: Yield 32%. Mp: 123-125℃; ESI-MS: m/z 330 [M+H]⁺; ¹H NMR (300 MHz, DMSO-d₆): δ 10.71 (s, 1H), 7.49-7.33 (m, 2H), 7.25 (d, 2H, J=7.9 Hz), 7.17 (d, 2H, J=7.9 Hz), 6.97 (s, 1H), 6.57 (s, 1H), 3.57 (t, 2H), 2.70-2.52 (m, 2H), 2.28 (s, 3H). 9f: Yield 27%. Mp: 192-194℃; ESI-MS: m/z 357.5 [M+H]⁺, 380 [M+Na]⁺; ¹H NMR (300 MHz, DMSOd₆): δ 7.18 (d, 2H, J=8.3 Hz), 7.12 (d, 1H), 7.04 (d, 2H, J=8.3 Hz), 6.71-6.51 (m, 2H), 6.26-6.00 (m, 2H), 5.82-5.52 (m, 2H), 4.33 (m, 1H), 4.22-4.09 (m, 1H), 4.04 (m, 1H), 3.99-3.89 (m, 1H), 3.73 (dt, 1H), 3.68-3.54 (m, 1H), 2.18 (s, 3H).
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1.
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