144511-13-7

Basic information

• Product Name: 6,9-difluorobenzoisoquinoline-5,10-dione
• Synonyms: 6,9-difluorobenzoisoquinoline-5,10-dione;6,9-Difluorobenzo[g]isoquinolin-5,10-dione;6,9-difluorobenzoisoquinoline-5,10-dione;6,9-difluorobenzo;Pixantrone pharMaceutical interMediate;6,9-Difluorobenz[g]isoquinoline-5,10-dione;PSQ04
• CAS NO: 144511-13-7
• Molecular Formula: C₁₃H₅F₂NO₂
• Molecular Weight: 245.1811064
• Mol File: 144511-13-7.mol

Chemical Properties

• Boiling Point: 433℃
• Flash Point: 215℃
• Appearance: /
• Density: 1.525
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: -0.58±0.20(Predicted)
• CAS DataBase Reference: 6,9-difluorobenzoisoquinoline-5,10-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 6,9-difluorobenzoisoquinoline-5,10-dione(144511-13-7)
• EPA Substance Registry System: 6,9-difluorobenzoisoquinoline-5,10-dione(144511-13-7)

Safety Data

• Hazardous Substances Data: 144511-13-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
6,9-difluorobenzoisoquinoline-5,10-dione is used as a pharmaceutical candidate for drug development due to its unique structure and chemical properties. Its molecular structure and reactivity may contribute to the discovery of novel therapeutic agents.
Used in Organic Synthesis:
6,9-difluorobenzoisoquinoline-5,10-dione is used as a building block in organic synthesis for the creation of new organic compounds. Its unique structure and reactivity can facilitate the development of innovative organic molecules with potential applications in various fields.
Further research and exploration of 6,9-difluorobenzoisoquinoline-5,10-dione's chemical properties may lead to the discovery of additional applications and uses in different industries.

Upstream product

• 4664-08-8 cinchomeronic anhydride 
• 540-36-3 para-difluorobenzene 
• 626-60-8 3-Chloropyridine 
• 111608-80-1 4,7-difluoro-3-cyano-1(3H)-isobenzofuranone 
• 144511-12-6 3-(2',5'-difluorobenzoyl)isonicotinic acid 
• 144511-11-5 4-(2',5'-Difluorobenzoyl)nicotinic acid 
• 490-11-9 3,4-pyridinecarboxylic acid 
• 188622-59-5 3-(2,5-Difluoro-benzyl)-isonicotinic acid 

Downstream Products

• 144510-94-1 6,9-bis<<2-ethyl>amino>benzoisoquinoline-5,10-dione 
• 145047-56-9 6,9-bis<<2-(dimethylamino)ethyl>amino>benzoisoquinoline-5,10-dione 2-oxide 
• 188964-72-9 2-<2--N-(2-hydroxyethyl)amino>ethyl>-5-<<(4-methylphenyl)sulfonyl>oxy>indazolo<4,3-gh>isoquinolin-6(2H)-one 
• 156090-04-9 2-[2-(N-tert-butoxycarbonylamino)ethyl]-5-(p-toluenesulfonyloxy)-isoquino[8,7,6-cd]indazole-6(2H)-one 
• 220074-31-7 2-<2--N-methylamino>ethyl>-5-<<(4-methylphenyl)sulfonyl>oxy>indazolo<4,3-gh>isoquinolin-6(2H)-one 
• 156090-05-0 2-<2-<(2-hydroxyethyl)amino>ethyl>-5-<<(4-methylphenyl)sulfonyl>oxy>indazolo<4,3-gh>isoquinolin-6(2H)-one 
• 220074-30-6 2-<3-(dimethylamino)propyl>-5-<<(4-methylphenyl)sulfonyl>oxy>indazolo<4,3-gh>isoquinolin-6(2H)-one 
• 156090-03-8 2-<2-(dimethylamino)ethyl>-5-<<(4-methylphenyl)sulfonyl>oxy>indazolo<4,3-gh>isoquinolin-6(2H)-one 
• 156090-18-5 5-[[2-(dimethylamino)ethyl]amino]-2-[2-[(2-hydroxyethyl)amino]ethyl]indazolo[4,3-gh]isoquinolin-6(2H)-one dihydrochloride 
• 172779-22-5 2-(2-hydroxyethyl)-5-<<(4-methylphenyl)sulfonyl>oxy>indazolo<4,3-gh>isoquinolin-6(2H)-one 
• 156090-75-4 9-fluoro-6-<<(4-methylphenyl)sulfonyl>oxy>benzisoquinoline-5,10-dione 
• 144510-89-4 6,9-bis<<2-(diethylamino)ethyl>amino>benzoisoquinoline-5,10-dione 

Relevant articles and documents

Synthesis of fluorine-substituted anthraquinones and azaanthraquinones

Using 1,4-dipolar-aryne cycloaddition methodology, a convenient, short synthesis of several fluoroanthraquinones is presented which involves the reaction of haloarenes and 3-cyanophthalides in the presence of lithium diisopropylamide (LDA) in tetrahydrofuran (THF).The fluorine substituent(s) can be introduced by using fluorine-substituted haloarenes and/or 3-cyanophthalides.Similarly, fluorine-substituted pyridines can be prepared by treating fluorine-substituted cyanophthalides and halopyridines in the presence of lithium diisopropylamide.

A cedar Joan maleic acid salt preparation method

The invention provides a pixantrone maleate synthesis method which has the advantages of high yield, low impurity content, simple process and easiness in large-scale production. In the method, pyridine-3,4-dicarboxylic acid is used as a starting raw material which reacts with acetic anhydride to obtain pyridine-3,4-dicarboxylic anhydride; the pyridine-3,4-dicarboxylic anhydride conducts an Friedel-Crafts acylation reaction with 1,4-difluorobenzene, and the obtained mixture is subjected to catalytic cyclization to obtain a key intermediate; the intermediate reacts with amino-protected ethylenediamine to obtain protecting group-containing pixantrone; and after that, deprotection and salifying are performed to obtain the target product. In the Friedel-Crafts acylation reaction of the method, an n-hexane solution of sulfuric acid is used as a catalyst, thus the use is convenient, the aftertreatment is simple, and the potential risk in production is eliminated; the Cbz or Fmoc protected ethylenediamine reacts with substituted anthraquinone and then the protecting group is removed through catalytic hydrogenation to obtain pixantrone; the process effectively inhibits side reactions and reduces the impurity content; and meanwhile, the aftertreatment is simplified, and the yield increase is facilitated.

New anthracenedione derivatives with improved biological activity by virtue of stable drug-DNA adduct formation

Mitoxantrone is an anticancer agent that acts as a topoisomerase II poison, however, it can also be activated by formaldehyde to form DNA adducts. Pixantrone, a 2-aza-anthracenedione with terminal primary amino groups in its side chains, forms formaldehyde-mediated adducts with DNA more efficiently than mitoxantrone. Molecular modeling studies indicated that extension of the "linker" region of anthracenedione side arms would allow the terminal primary amino greater flexibility and thus access to the guanine residues on the opposite DNA strand. New derivatives based on the pixantrone and mitoxantrone backbones were synthesized, and these incorporated primary amino groups as well as extended side chains. The stability of DNA adducts increased with increasing side chain length of the derivatives. A mitoxantrone derivative bearing extended side chains (7) formed the most stable adducts with ～100-fold enhanced stability compared to mitoxantrone. This finding is of great interest because long-lived drug-DNA adducts are expected to perturb DNA-dependent functions at all stages of the cell cycle.

1,4-bis-N-oxide azaanthracenediones and the use thereof

Disclosed are compounds having Formula IV: and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and p are as defined herein, for use in methods for treating, preventing or ameliorating hyperproliferative disorders, such as cancer. The invention also relates to pharmaceutical compositions and formulations comprising a compound having Formula IV, and in combination with one or more other active agents and/or treatments.

Synthesis of regioisomeric 6,9-(chlorofluoro)-substituted benzo[g]quinoline-5,10-diones, benzo[g]isoquinoline-5,10-diones and 6-chloro-9-fluorobenzo[g]quinoxaline-5,10-dione

Treatment of difluoro or chloro fluoro-substituted benzyl bromides 5a-c with zinc dust in tetrahydrofuran leads to the corresponding benzylic zinc bromides 6a-c. These organometallics on treatment with chlorosubstituted heterocyclic esters 4A and 4B mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters 7Aa-c and 7Ba-c. Treatment of 4c with 6c under Pd catalysis leads to 7Cc. The acids 8, prepared by hydrolysis of these esters, with treatment of fuming sulfuric acid undergo cyclizations and oxidations to yield the desired regioisomeric dihalo-substituted heterocyclic quinones 2.

Hetero-annulated indazoles

This invention is directed to heteroannulated indazoles namely to 2,5-disubstituted quinolino-, isoquinolino-, phthalazino-, and quinoxalino- annulated indazole-6(2H)-ones and related mono N-oxides. These compounds have been shown to have antitumor activity.

6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione and its dimaleate salt

In the search for novel heteroanalogs of anthracendiones, 6,9-bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione dimaleate salt (BBR 2778), was selected as the most promising compound. New methods of synthesis produce the compound in purity greater than 99%.

2-aminoalkyl-5-aminoalkylamino substituted-isoquinoindazole-6(2H)-ones

This invention is directed to 2-aminoalkyl-5-aminoalkylamino substituted isoquino [8,7,6-cd]indazole-6-(2H)-ones and to 2-aminoalkyl-5-aminoalkylamino substituted-isoquino [5,6,7-cd] indazole-6(2H)-ones. These compounds have been shown to have antitumor activity.

6,9-Bisbenzoisoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations

Synthetic procedures have been developed which lead to the 2-aza congeners 3 and several related N-oxides 4.The analoques 3 exhibited a wide range of in vitro cytotoxicity against L1210 leukemia, the human colon adenocarcinoma cell line LoVo, and the doxorubicin resistant LoVo/DX cell line.Selected analogues of 3 showed significant P388 antileukemic activity in mice with 3c exhibiting high activity.This activity was also retained in the related N-oxide 4a.These heterocyclic bioisosteric models are representative of the first anthracene-9,10-diones which display antileukemic activity comparable to mitoxantrone.

6,9 Bis(substituted-amino)benzo-[g]isoquinoline-5,10-diones

A compound according to formula (I): wherein R is, C1-C10 alkyl; phenyl or C7-C10 aralkyl;, C2-C10 aklyl substituted with one or two substituents selected from the group consisting of OR1 and -NR2R3;, C2-C10 alkyl interrupted by one or two oxygen atoms or by a member selected from the group consisting of -NR4-, cis-CH=CH, trans-CH=CH- and -C=C-, and optionally substituted with one or two hydroxy (OH) or -NR2R3 groups; and wherein, R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, phenyl, C7-C10 aralkyl, -CHO, -COR5-, -COOR5, -S(O2)R5 and C2-C6 alkyl optionally substituted with -NR2R3;, R2 and R3 are the same or different and are selected from the group consisting of hydrogen, C1-C10 alkyl, C7-C10 aralkyl, phenyl, C2-C10 alkyl substituted with one or two hydroxy (OH) groups, -CHO, -COR5, -COOR5, and -S(O2)R5, R2 and R3 taken together with the nitrogen atom to which they are bound form an ethyleneimine ring or a 5- or 6-membered aromatic or non-aromatic heterocyclic ring optionally containing another heteroatom selected from the group consisting of sulfur, oxygen and nitrogen, R2 is H and R3 is -C(=NH)NH2 or R2 is -C(=NH)NH2 and R3 is H;, R4 is selected from the group consisting of hydrogen, C1-C10 alkyl, C2-C10 hydroxyalkyl, C2-C10 alkyl substituted with -NR2R3, C7-C10 aralkyl, phenyl, -COR5, -COOR5 and -S(O2)R5;, R5 is selected from the group consisting of C1-C10 alkyl, C7-C10 aralkyl, α-, β-, or γ-naphthyl, phenyl, o-, m-, or p-tolyl as free bases and their salts with pharmaceutically acceptable acids, have been found to have cytostatic and anti-tumor activity.