Category: piperidinesIn 2018 ,《Structural Modification of Natural Product Tanshinone I Leading to Discovery of Novel Nitrogen-Enriched Derivatives with Enhanced Anticancer Profile and Improved Drug-like Properties》 was published in Journal of Medicinal Chemistry. The article was written by Ding, Chunyong; Tian, Qianting; Li, Jie; Jiao, Mingkun; Song, Shanshan; Wang, Yingqing; Miao, Zehong; Zhang, Ao. The article contains the following contents:
The clin. development of natural product tanshinone I (1) for cancer therapy is hampered by its weak potency and poor drug-like properties. Herein, a more broad and systemic structural modification on 1 was conducted to generate four series of new tanshinone derivatives Among them, the lactam derivative 22h (4-(3-(diethylamino)propyl)-2-methylfuro[3,2-c]phenanthridine-5,10,11(4H)-trione) demonstrated the most potent antiproliferative activity against KB and drug-resistant KB/VCR cancer cells, which are approx. 13- to 49-fold more potent than 1. Compound 22h possesses significantly improved drug-like properties including aqueous solubility (15.7 mg/mL), metabolic stability of liver microsomes, and PK characters (T1/2 = 2.58 h; F = 21%) when compared to 1. Preliminary mechanism studies showed that 22h significantly induced apoptosis of HCT116 cells, at least partially, through activation of caspase-3/-7. More importantly, administration of 22h at 10 mg/kg significantly suppressed the tumor growth of HCT116 xenograft in vivo without significant loss of body weight of the tested nude mice. The experimental part of the paper was very detailed, including the reaction process of 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Category: piperidines)
2-(Piperidin-4-yl)ethanol(cas: 622-26-4) have been used as an intermediate in the synthetic preparation of cellular-active allosteric inhibitors of FAKCategory: piperidines
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem