123949-01-9

Usage

Uses

Used in Pharmaceutical Industry:
The compound's application in the pharmaceutical industry is primarily due to its potential in the development of novel cancer treatments. By inhibiting topoisomerase I, these analogs can disrupt DNA replication, leading to the prevention of tumor growth and the potential eradication of cancer cells. This makes (4S)-10-(EthoxyMethyl)-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione a valuable asset in the fight against cancer and a promising candidate for further research and development in the pharmaceutical sector.

Upstream product

• 50-00-0 formaldehyd 
• 64-17-5 ethanol 
• 19685-09-7 (S)-10-hydroxycamptothecin 
• 123948-87-8 topotecan 
• 7689-03-4 camptothecin 

Relevant academic research and scientific papers

The solvolysis of topotecan in alcohols and acetic anhydride

Six derivatives of 10-hydroxycamptothecin were prepared via solvolysis of topotecan in corresponding alcohols and acetic anhydride. We attributed the specific reactivity of topotecan to the internal hydrogen-bonding between 10-hydroxy and the nitrogen atom in position 9. As a result the reaction underwent through an intermediate ortho-quionomethlide species to reach equilibrium. Bioactivity screening data showed all products could potentially inhibit the proliferation of several cancer cell lines in vitro and a bigger size group in 9-position would be favorable for the anti-tumor activities observably.

Synthesis of water-soluble (aminoalkyl)camptothecin analogues: Inhibition of topoisomerase I and antitumor activity

Water-soluble analogues of the antitumor alkaloid camptothecin (1) were prepared in which aminoalkyl groups were introduced into ring A or B. Most of the analogues were prepared by oxidation of camptothecin to 10-hydroxy-camptothecin (2) followed by a Mannich reaction to give N-substituted 9-(aminomethyl)-10-hydroxycamptothecins (4-12) or by subsequent modification of Mannich product 4 (13, 15, 17, 19, 21). Others were obtained by modification of the hydroxyl group of 2 (25, 26) or by total synthesis (35, 42, 43). These analogues, as well as some of their synthetic precursors, were evaluated for inhibition of topoisomerase I, cytotoxicity, and antitumor activity. Although there was not a quantitative correlation between these assays, compounds that inhibited topoisomerase I were also cytotoxic and demonstrated antitumor activity in vivo. Further evaluation of the most active water-soluble analogue led to the selection of 9-[(dimethylamino)methyl]-10-hydroxycamptothecin (4, SK and F 104864) for development as an antitumor agent. In addition to its water solubility, ease of synthesis from natural camptothecin, and high potency, 4 demonstrated broad-spectrum activity in preclinical tumor models and is currently undergoing Phase I clinical trials in cancer patients.