Novel spiropyrazolone antitumor scaffold with potent activity: Design, synthesis and structure-activity relationship
- Eur J Med Chem. 2016 Jun 10:115:141-7. doi: 10.1016/j.ejmech.2016.03.039.
- 1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
- 2. Clinical Research Center, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
- 3. Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address: [email protected].
- 4. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: [email protected].
- 5. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: [email protected].
Phenotypic screening of high quality compound library is an effective strategy to discover novel bioactive molecules. Previously, we developed the divergent organocatalytic cascade approach to efficiently construct a focused library with scaffold diversity and successfully identified a novel spiropyrazolone antitumor scaffold. Herein, a series of spiropyrazolone derivatives were designed, synthesized and assayed. Most of them showed good in vitro antitumor activity with a broad spectrum. Preliminary structure-activity relationship for the substitutions and the stereo configuration were obtained. Compound 5k showed good antitumor activity and could effectively induce Cancer cell Apoptosis, which represents a good starting point for the development of novel antitumor agents.