80758-83-4

Usage

Uses

Used in Pharmaceutical Applications:
(S)-11-ForMy-4-ethyl-4-hydroxy-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione is used as a potential pharmaceutical agent for [application reason]. Its unique molecular structure may offer novel interactions with biological targets, potentially leading to the development of new therapeutics.
Used in Organic Chemistry Research:
In the field of organic chemistry, (S)-11-ForMy-4-ethyl-4-hydroxy-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione is used as a compound for [application reason], such as exploring new synthetic pathways or studying its reactivity with other molecules.
Used in Material Science:
(S)-11-ForMy-4-ethyl-4-hydroxy-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione is used as a component in the development of new materials for [application reason], possibly due to its unique structural features that could contribute to specific material properties.

Upstream product

• 67-56-1 methanol 
• 7689-03-4 camptothecin 
• 84017-99-2 7-(dimethoxymethyl)camptothecin 
• 78287-14-6 7-hydroxymethylcamptothecin 
• 103-80-0 phenylacetyl chloride 
• 80735-03-1 7-methoxycamptothecin 
• 64-19-7 acetic acid 
• 84018-01-9 7-Ethoxymethylcamptothecin 

Downstream Products

• 372105-27-6 anti-7-(2-aminoethoxy)iminomethylcamptothecin 
• 372105-27-6 namitecan 
• 84017-99-2 7-(dimethoxymethyl)camptothecin 

Relevant academic research and scientific papers

Synthesis, biological activities, and quantitative structure-Activity relationship (QSAR) Study of novel camptothecin analogues

In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-To-excellent activity against three insect species tested, with LC50 values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and 2 pred r of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents.

Electron paramagnetic resonance (EPR) study of spin-labeled camptothecin derivatives: A different look of the ternary complex

Camptothecin (CPT) derivatives are clinically effective poisons of DNA topoisomerase I (Top1) able to form a ternary complex with the Top1-DNA complex. The aim of this investigation was to examine the dynamic aspects of the ternary complex formation by means of site-directed spin labeling electron paramagnetic resonance (SDSL-EPR). Two semisynthetic CPT derivatives bearing the paramagnetic moiety were synthesized, and their biological activity was tested. A 22-mer DNA oligonucleotide sequence with high affinity cleavage site for Top1 was also synthesized. EPR experiments were carried out on modified CPT in the presence of DNA, of Top1, or of both. In the last case, a slow motion component in the EPR signal appeared, indicating the formation of the ternary complex. Deconvolution of the EPR spectrum allowed to obtain the relative drug amounts in the complex. It was also possible to demonstrate that the residence time of CPT "trapped" in the ternary complex is longer than hundreds of microseconds.

CRYSTALLINE FORM II OF 7-(DIMETHOXY-METHYL) CAMPTOTHECIN, ITS USE AS INTERMEDIATE AND PRODUCTS OBTAINED THEREFROM

This invention relates to a process for preparing a crystalline form of (4S)-11-(dimethoxymethyl)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]qui-no line-3,14(4H,12H)-dione (also named 7-(dimethoxy-methyl)camptothecin). With the provision of a particular crystallization step, in appropriate way, a new crystalline form of the above compound is obtained. The process for the preparation of the polymorph Form II comprises transforming camptothecin to the corresponding 7-(dimethoxy-methyl)-camptothecin, and crystallizing it from methanol.

Chemical modification of an antitumor alkaloid camptothecin: Synthesis and antitumor activity of 7-C-substituted camptothecins

A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl- (4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.

CHEMICAL MODIFICATION OF ANTITUMOR ALKALOID CAMPTOTHECIN. ACID-CATALYZED CONVERSION OF 7-HYDROXYMETHYLCAMPTOTHECIN INTO THE ALDEHYDE AND ITS ACETALS

Camptothecin-7-carbaldehyde (3) was prepared from 7-hydroxymethylcamptothecin (2) by treatment with such cationoid agent as sulfuric acid, acetic acid, p-toluenesulfonyl chloride, phosphoryl chloride, thionyl chloride, or triphenylphosphinecarbon tetrachloride.On heating with sulfuric acid in an alcoholic solution, 2 afforded 7-alkoxymethylcamptothecin (4) and 7-dialkoxymethylcamptothecin (5), the product-ratio depending upon the acid-concentration.