705-09-9Relevant articles and documents
Silver-Enabled General Radical Difluoromethylation Reaction with TMSCF2H
Yang, Jun,Zhu, Shengqing,Wang, Fang,Qing, Feng-Ling,Chu, Lingling
supporting information, p. 4300 - 4306 (2020/12/25)
A silver-mediated oxidative difluoromethylation of styrenes and vinyl trifluoroborates with TMSCF2H is reported for the first time. This method enables direct and facile access to CF2H-alkenes from abundant alkenes with excellent functional-group compatibility. Moreover, this Ag/TMSCF2H protocol could further enable a series of radical difluoromethylation reactions of a wide array of substrates, offering a generic and complementary platform for the construction of diversified C?CF2H bonds.
Late-Stage 18F-Difluoromethyl Labeling of N-Heteroaromatics with High Molar Activity for PET Imaging
Trump, Laura,Lemos, Agostinho,Lallemand, Bénédicte,Pasau, Patrick,Mercier, Jo?l,Lemaire, Christian,Luxen, André,Genicot, Christophe
supporting information, p. 13149 - 13154 (2019/08/20)
Despite a growing interest in CHF2 in medicinal chemistry, there is a lack of efficient methods for the insertion of CHF18F into druglike compounds. Herein described is a photoredox flow reaction for 18F-difluoromethylation of N-heteroaromatics that are widely used in medicinal chemistry. Following the two-step synthesis for a new 18F-difluoromethylation reagent, the photoredox reaction is completed within two minutes and proceeds by C?H activation, circumventing the need for pre-functionalization of the substrate. The method is operationally simple and affords straightforward access to radiolabeled N-heteroaromatics with high molar activity suitable for biological in vivo studies and clinical application.
Synthesis of new 2-substituted 3-(tri(di)fluoromethyl)-quinoxalines from 3-(trifluoromethyl)quinoxalin-2(1H)-oneand 3-(tri(di)fluoromethyl)quinoxaline-2-carboxylic acids
Didenko, Andrey V.,Vorobiev, Mikhail V.,Sevenard, Dmitri V.,Sosnovskikh, Vyacheslav Ya.
, p. 259 - 268 (2016/01/12)
[Figure not available: see fulltext.] Starting from 3-(trifluoromethyl)quinoxalin-2(1H)-one, a wide range of new 2-substituted 3-(trifluoromethyl)quinoxalines were obtained, including amino, bromo, chloro, hydrazino, phenyl, α-furyl, formyl, methylsulfanyl, and methylsulfonyl derivatives. 3-(Tri(di)-fluoromethyl)quinoxaline-2-carboxylic acids were obtained for the first time and used for the synthesis of 2-amino-3-(tri(di)-fluoromethyl)quinoxalines and 2-(2-aminothiazol-4-yl)-3-(trifluoromethyl)quinoxaline.
Process for production of DFMB derivatives
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Paragraph 0037, (2015/02/05)
A process for the production of a compound of formula (III) which comprises a step of reacting a compound of formula (I) with an excess amount of a compound of formula (II) in absence of aromatic solvent, wherein n is 0, 1, 2, 3 or 4; X is NH, O or S; eac
QUINAZOLINES AND AZAQUINAZOLINES AS DUAL INHIBITORS OF RAS/RAF/MEK/ERK AND PI3K/AKT/PTEN/MTOR PATHWAYS
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Page/Page column 59; 60, (2014/10/29)
The present application provides novel quinazolines and azaquinazolines and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in for co-regulating RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways by administering a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, T and R4, and R6 to R8' are defined herein, to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment/ the disease is cancer.
PHOSPHOINOSITIDE 3-KINASE (PI3K) INHIBITORS
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Page/Page column 38-39, (2014/01/18)
The invention relates to compounds, and uses of the compounds, that are inhibitors of the enzyme phosphoinositide 3-kinase (PI3K). More particularly the compounds are selective inhibitors of one or more isoforms of PI3K. In particular embodiments the compounds are selective inhibitors of one isoform of PI3K
PROCESS FOR PRODUCTION OF DFMB DERIVATIVES
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Paragraph 0030, (2013/09/12)
Disclosed is a process for the production of a compound of formula (ΙΠ). The process comprises a step of reacting a compound of formula (I) with an excess amount of a compound of formula (II) in absence of aromatic solvent:wherein - n is 0 1, 2, 3 or 4; - X is NH, O or S; - each R] group may be the same or different, and is independently selected from the group consisting of hydrogen, hydroxyl, alkoxy, alkyl, carbonyl, carboxyl, carboxylic acid ester groups, amido, cyano, halogenated aliphatic, nitro, or amino groups; - R2 group is selected from the group consisting of hydroxyl, CI, F, Br, amino or alkoxy.
Efficient syntheses of 2-fluoroalkylbenzimidazoles and -benzothiazoles
René, Olivier,Souverneva, Alexandra,Magnuson, Steven R.,Fauber, Benjamin P.
supporting information, p. 201 - 204 (2013/02/22)
We report an efficient one-step route to 2-fluoroalkylbenzimidazoles and -benzothiazoles via the condensation of fluorinated carboxylic acids and aromatic diamines or aminothiophenols. Additionally, we describe the syntheses of fluoroalkyl-azabenzimidazoles, -purines, and -imidazolopyrazines. This method is high-yielding with broad scope and is operationally simple with potential application to parallel synthesis.
L-aminoacyl-triazine derivatives are isoform-selective PI3Kβ inhibitors that target nonconserved Asp862 of PI3Kβ
Pinson, Jo-Anne,Zheng, Zhaohua,Miller, Michelle S.,Chalmers, David K.,Jennings, Ian G.,Thompson, Philip E.
supporting information, p. 206 - 210 (2013/03/29)
A series of aminoacyl-triazine derivatives based upon the pan-PI3K inhibitor ZSTK474 were identified as potent and isoform-selective inhibitors of PI3Kβ. The compounds showed selectivity based upon stereochemistry with l-amino acyl derivatives preferring PI3Kβ, while their d-congeners favored PI3Kδ. The mechanistic basis of this inhibition was studied using site-directed mutants. One Asp residue, D862, was identified as a critical participant in binding to the PI3Kβ-selective inhibitors, distinguishing this class from other reported PI3Kβ-selective inhibitors. The compounds show strong inhibition of cellular Akt phosphorylation and growth of PTEN-deficient MD-MBA-468 cells.
Synthesis and biological evaluation of novel analogues of the pan class i phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(Difluoromethyl)-1-[4,6-di(4- morpholinyl)-1,3,5-triazin-2-yl]-1 H -benzimidazole (ZSTK474)
Rewcastle, Gordon W.,Gamage, Swarna A.,Flanagan, Jack U.,Frederick, Raphael,Denny, William A.,Baguley, Bruce C.,Kestell, Philip,Singh, Ripudaman,Kendall, Jackie D.,Marshall, Elaine S.,Lill, Claire L.,Lee, Woo-Jeong,Kolekar, Sharada,Buchanan, Christina M.,Jamieson, Stephen M. F.,Shepherd, Peter R.
experimental part, p. 7105 - 7126 (2011/12/04)
A structure-activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2- yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110α, p110β, and p110δ) and also displayed significant potency against two mutant forms of the p110α isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Rag1 -/- mice, and at a dose of 50 mg/kg given by ip injection at a qd ?- 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.
