149809-31-4

Usage

Uses

Used in Pharmaceutical Industry:
1-(7-AMINO-2,3-DIHYDRO-BENZO[1,4]DIOXIN-6-YL)-2-CHLORO-ETHANONE is used as a research and development compound for the synthesis of new drugs and pharmaceutical formulations. Its unique structure and properties contribute to the development of innovative therapeutic agents.
Used in Organic Synthesis:
In the field of organic synthesis, 1-(7-AMINO-2,3-DIHYDRO-BENZO[1,4]DIOXIN-6-YL)-2-CHLORO-ETHANONE serves as a precursor for the production of various other compounds. Its chemical properties and reactivity make it a versatile building block for creating a wide range of organic molecules.
Used in Drug Development:
Due to its potential applications in the synthesis of new drugs, 1-(7-AMINO-2,3-DIHYDRO-BENZO[1,4]DIOXIN-6-YL)-2-CHLORO-ETHANONE is utilized in drug development processes. Its unique structure allows for the exploration of new therapeutic agents with potential benefits in treating various medical conditions.

Upstream product

• 107-14-2 chloroacetonitrile 
• 22013-33-8 6-amino-3,4-benzodioxane 

Downstream Products

• 149882-15-5 7-(chloromethyl)-10,11-(ethylenedioxy)-(20S)-camptothecin 
• 149882-10-0 lurtotecan 

Relevant academic research and scientific papers

Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C

The topoisomerase I inhibitor GI147211C (4) was discovered at Glaxo Wellcome and shown to have promising anti-cancer properties. In order to fully assess the clinical potential of 4, an improved synthesis of the drug substance was required. Herein is described a convergent catalytic asymmetric synthesis of 4 which utilizes as key steps, two Heck reactions, a Sharpless asymmetric dihydroxylation reaction, and a Mitsunobu reaction. A 2-chloroquinoline is shown to be a viable substrate for the final Heck reaction to generate the camptothecin nucleus.

The structure-activity relationships of A-ring-substituted aromathecin topoisomerase i inhibitors strongly support a camptothecin-like binding mode

Aromathecins are inhibitors of human topoisomerase I (Top1). These compounds are composites of several heteroaromatic systems, namely the camptothecins and indenoisoquinolines, and they possess notable Top1 inhibition and cytotoxicity when substituted at position 14. The SAR of these compounds overlaps with indenoisoquinolines, suggesting that they may intercalate into the Top1-DNA complex similarly. Nonetheless, the proposed binding mode for aromathecins is purely hypothetical, as an X-ray structure is unavailable. In the present communication, we have synthesized eight novel series of A-ring-substituted (positions 1-3) aromathecins, through a simple, modular route, as part of a comprehensive SAR study. Certain groups (such as 2,3-ethylenedioxy) moderately improve Top1 inhibition, and, often, antiproliferative activity, whereas other groups (2,3-dimethoxy and 3-substituents) attenuate bioactivity. Strikingly, these trends are very similar to those previously observed for the A-ring of camptothecins, and this considerable SAR overlap lends further support (in the absence of crystallographic data) to the hypothesis that aromathecins bind in the Top1 cleavage complex as interfacial inhibitors in a 'camptothecin-like' pose.

New homocamptothecins: Synthesis, antitumor activity, and molecular modeling

Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered β-hydroxylactone in place of the conventional six-membered α-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 9l, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity.

Synthesis and bioevaluation of 22-hydroxyacuminatine analogs

A series of 22-hydroxyacuminatine analogs was prepared by using different Friedlaender condensations. Several of the new compounds were tested for antiproliferative activity on cancer cell lines and for topoisomerase I inhibitory activity.

Preparation of a camptothecin derivative by intramolecular cyclisation

PCT No. PCT/US95/05427 Sec. 371 Date Nov. 1, 1996 Sec. 102(e) Date Nov. 1, 1996 PCT Filed May 2, 1995 PCT Pub. No. WO95/29919 PCT Pub. Date Nov. 9, 1995The present invention relates to a method for the preparation of camptothecin and camptothecin-like compounds and to novel intermediates used in this preparation. In particular, the invention provides a process for the preparation of the camptothecin derivative of formula (I') known by the chemical name "7-(4-methylpiperazino-methylene)-10,11-ethylenedioxy-20(R,S)-camptothecin", which comprises cyclising the compound of formula (II'), wherein X is halogen, particularly chloro, bromo, or iodo; and when the compound of formula (I') is obtained as a mixture of enantiomers optionally resolving the mixture to obtain the desired enantiomer, and/or if desired, converting the resulting compound of formula (I') or a salt thereof into a physiologically acceptable salt or solvate thereof.

Intermediates in pharmaceutical camptothecin preparation

A process of providing novel compounds of Formula (I) below, which are useful as intermediates in the preparation of camptothecin and camptothecin-like compounds, STR1 wherein: R1 represents alkyl, particularly methyl, R2 represents H or alkyl, particularly methyl, R3 represents H or alkyl, particularly H; Q represents triflate or halo particularly bromo and iodo more particularly iodo and Y represents H, chloro or OR4, wherein R4 represents alkyl or triflate, or particularly H.

Synthesis and Antitumor Activity of Novel Water Soluble Derivatives of Camptothecin as Specific Inhibitors of Topoisomerase I

The synthesis and antitumor activities of the novel water soluble camptothecin derivatives 7--10,11-(methylenedioxy)-(20S)-camptothecin trifluoroacetate (6) and 7--10,11-(ethylenedioxy)-(20S)-camptothecin trifluoroacetate (7) are described.The solubilities of compounds 6 and 7 were measured to be 4.5 and 5.8 mg/mL, respectively, in pH 5 acetate buffer in contrast to 0.003 mg/mL for camptothecin in the same buffer.In the purified topoisomerase I cleavable complex enzyme assay, compounds 6 and 7 demonstrated potent inhibition of topoisomerase I with IC50's of 300 and 416 nM, respectively, in comparison to 679 nM for camptothecin and 1028 nM for topotecan.In human tumor cell cytotoxicity assays, compounds 6 and 7 demonstrated potent antitumor activity against ovarian (SKOV3), ovarian with upregulated MDRp-glycoprotein (SKVLB), melanoma (LOX), breast (T47D), and colon (HT29) with IC50's ranging from 0.5 to 102 nM.Compounds 6 and 7 induced tumor regressions in the HT29 human colon tumor xenograft model and demonstrated similar rank order of potency compared to in vitro assay results.