Category: 144511-13-7

Khanapure, Subash P.; Han, Wei; Swartling, Dan J.; Biehl, Edward R. published the artcile< Synthesis of fluorine-substituted anthraquinones and aza-anthraquinones>, Name: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione, the main research area is fluoro anthraquinone azaanthraquinone; anthraquinone fluoro; benzquinolinone fluoro; mitoxantrone fluoroanthraquinone intermediate; ametantrone fluoroanthraquinone intermediate; aza anthraquinone fluoro.

Using 1,4-dipolar-aryne cycloaddition methodol., a convenient, short synthesis of several fluoroanthraquinones I (R1 = H, methoxy, methoxymethoxy; n = integer) is presented which involves the reaction of haloarenes and 3-cyanophthalides in the presence of lithium diisopropylamide (LDA) in THF. The fluorine substituent(s) can be introduced by using fluorine-substituted haloarenes and/or 3-cyanophthalides. Similarly, fluorine-substituted pyridines, i.e. (fluoro)benz[g]isoquinoline-5,10-diones, II (R1 = H, methoxy, methoxymethoxy; n = integer) can be prepared by treating fluorine-substituted cyanophthalides and halopyridines in the presence of lithium diisopropylamide.

Journal of Fluorine Chemistry published new progress about 1,3-Dipolar cycloaddition reaction. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Name: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Pumuye, Paul P.; Evison, Benny J.; Konda, Shyam K.; Collins, J. Grant; Kelso, Celine; Medan, Jelena; Sleebs, Brad E.; Watson, Keith; Phillips, Don R.; Cutts, Suzanne M. published the artcile< Formaldehyde-activated WEHI-150 induces DNA interstrand crosslinks with unique structural features>, Computed Properties of 144511-13-7, the main research area is formaldehyde WEHI150 DNA interstrand crosslink; Anthracenediones; Cancer chemotherapy; DNA sequence specificity; Drug-DNA adducts; Mitoxantrone analogues.

Mitoxantrone is an anticancer anthracenedione that can be activated by formaldehyde to generate covalent drug-DNA adducts. Despite their covalent nature, these DNA lesions are relatively labile. It was recently established that analogs of mitoxantrone featuring extended side-chains terminating in primary amino groups typically yielded high levels of stable DNA adducts following their activation by formaldehyde. In this study we describe the DNA sequence-specific binding properties of the mitoxantrone analog WEHI-150 which is the first anthracenedione to form apparent DNA crosslinks mediated by formaldehyde. The utility of this compound lies in the versatility of the covalent binding modes displayed. Unlike other anthracenediones described to date, WEHI-150 can mediate covalent adducts that are independent of interactions with the N-2 of guanine and is capable of adduct formation at novel DNA sequences. Moreover, these covalent adducts incorporate more than one formaldehyde-mediated bond with DNA, thus facilitating the formation of highly lethal DNA crosslinks. The versatility of binding observed is anticipated to allow the next generation of anthracenediones to interact with a broader spectrum of nucleic acid species than previously demonstrated by the parent compounds, thus allowing for more diverse biol. activities.

Bioorganic & Medicinal Chemistry published new progress about Crosslinking agents. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Computed Properties of 144511-13-7.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Krapcho, A. Paul; Menta, Ernesto; Oliva, Ambrogio; Di Domenico, Roberto; Fiocchi, Luigi; Maresch, Martin E.; Gallagher, Cynthia E.; Hacker, Miles P.; Beggiolin, Gino; Giuliani, Fernando C.; Pezzoni, Gabriella; Spinelli, Silvano published the artcile< Synthesis and Antitumor Evaluation of 2,5-Disubstituted-Indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-Aza-anthrapyrazoles)>, Recommanded Product: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione, the main research area is indazoloisoquinolinone antitumor preparation; azaanthrapyrazole antitumor preparation; anthrapyrazole aza antitumor preparation.

The synthesis and antitumor evaluation of 2,5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-APs) are described. The key intermediates in the synthesis are benz[g]isoquinoline-5,10-diones which are substituted at positions 6 and 9 with groups of different nucleofugacity for SNAr displacements. The initial displacement of fluoride by a substituted hydrazine leads to the pyrazole analogs. Substitution of the remaining leaving group by an amine or BOC-protected amines leads to the 9-aza-APs. These analogs were converted into their maleate or hydrochloride salts. In 2 cases, sidearm buildup was also employed in the synthetic pathway. In vitro evaluation of 9-aza-APs against the human colon tumor cell line LoVo uncovered for most of the compounds a cytotoxic potency lower than that of DuP-941 or mitoxantrone and comparable to that of doxorubicin. Only 3 analogs were as cytotoxic as DuP-941. Interestingly, while DuP-941 was highly cross-resistant in the LoVo cell line resistant to doxorubicin (LoVo/Dx), the 9-aza-APs carrying a distal lipophilic tertiary amine moiety in both chains were capable of overcoming the MDR resistance induced in this cell line. The 9-aza-APs have outstanding in vivo antitumor activity against both systemic P388 murine leukemia and MX-1 human mammary carcinoma transplanted in nude mice. At their optimal dosages, these were highly effective against P388 leukemia with T/C% of 200-381, while the T/C% value of DuP-941 was 147. In the MX-1 tumor model, 24 compounds elicited percentages of tumor weight inhibitions (TWI) ranging from 50% to 99%. Some of theses compounds emerged as the most effective ones, with TWI% 96, similar to that of DuP-941 (TWI% = 95). On the basis of their efficacy profile in addnl. exptl. tumors and lack of cardiotoxicity in preclin. models, 2 congeners have surfaced as potential clin. candidates.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Recommanded Product: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Krapcho, A. Paul; Gallagher, Cynthia E.; Mammach, Abdelhakim; Ellis, Michael; Menta, Ernesto; Oliva, Ambrogio published the artcile< 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>, Computed Properties of 144511-13-7, the main research area is benzoquinoxalinedione preparation; benzoisoquinolinedione preparation; benzoquinolinedione preparation.

Treatment of difluoro or chloro fluoro-substituted benzyl bromides with zinc dust in THF leads to the corresponding benzylic zinc bromides. These organometallics on treatment with chlorosubstituted heterocyclic esters and mediated by nickel catalysis undergo couplings to yield dihalobenzyl substituted heterocyclic esters. The acids, 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.

Journal of Heterocyclic Chemistry published new progress about 144511-13-7. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Computed Properties of 144511-13-7.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Krapcho, A. Paul; Petry, Mary E.; Getahun, Zelleka; Landi, John J. Jr.; Stallman, John; Polsenberg, Johanna F.; Gallagher, Cynthia E.; Maresch, Martin J.; Hacker, Miles P. published the artcile< 6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations>, SDS of cas: 144511-13-7, the main research area is anthracenedione preparation antitumor; benzoisoquinoline preparation antitumor.

Synthetic procedures have been developed which lead to the 2-aza congeners I (R = amine groups or N-containing heterocyclic groups) and several related N-oxides (II, R = NH2 or NMe2). I 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 analogs of I showed significant P388 antileukemic activity in mice with I (R = NH2, n = 2) exhibiting high activity. This activity was also retained in the related N-oxide II (R = NH2, n = 2). These heterocyclic bioisosteric models are representative of the first anthracene-9,10-diones which display antileukemic activity comparable to mitoxantrone.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, SDS of cas: 144511-13-7.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Mansour, Oula C.; Evison, Benny J.; Sleebs, Brad E.; Watson, Keith G.; Nudelman, Abraham; Rephaeli, Ada; Buck, Damian P.; Collins, J. Grant; Bilardi, Rebecca A.; Phillips, Don R.; Cutts, Suzanne M. published the artcile< New Anthracenedione Derivatives with Improved Biological Activity by Virtue of Stable Drug-DNA Adduct Formation>, Recommanded Product: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione, the main research area is anthracenedione amino derivative 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. Mol. 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 (I) 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.

Journal of Medicinal Chemistry published new progress about Acute promyelocytic leukemia. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Recommanded Product: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Krapcho, A. Paul; Petry, Mary E.; Getahun, Zelleka; Landi, John J. Jr.; Stallman, John; Polsenberg, Johanna F.; Gallagher, Cynthia E.; Maresch, Martin J.; Hacker, Miles P. published the artcile< 6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations>, Recommanded Product: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione, the main research area is anthracenedione preparation antitumor; benzoisoquinoline preparation antitumor.

Synthetic procedures have been developed which lead to the 2-aza congeners I (R = amine groups or N-containing heterocyclic groups) and several related N-oxides (II, R = NH2 or NMe2). I 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 analogs of I showed significant P388 antileukemic activity in mice with I (R = NH2, n = 2) exhibiting high activity. This activity was also retained in the related N-oxide II (R = NH2, n = 2). These heterocyclic bioisosteric models are representative of the first anthracene-9,10-diones which display antileukemic activity comparable to mitoxantrone.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Recommanded Product: 6,9-Difluorobenzo[g]isoquinoline-5,10-dione.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Mansour, Oula C.; Evison, Benny J.; Sleebs, Brad E.; Watson, Keith G.; Nudelman, Abraham; Rephaeli, Ada; Buck, Damian P.; Collins, J. Grant; Bilardi, Rebecca A.; Phillips, Don R.; Cutts, Suzanne M. published the artcile< New Anthracenedione Derivatives with Improved Biological Activity by Virtue of Stable Drug-DNA Adduct Formation>, Category: isoquinoline, the main research area is anthracenedione amino derivative 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. Mol. 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 (I) 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.

Journal of Medicinal Chemistry published new progress about Acute promyelocytic leukemia. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Category: isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem