7 research outputs found
Palladium-Catalyzed C–H Functionalization Using Guanidine as a Directing Group: Ortho Arylation and Olefination of Arylguanidines
Palladium-catalyzed C–H functionalization using guanidine as the directing group was achieved under mild reaction conditions. Various guanidine derivatives were produced in moderate to good yields by using simple unactivated arenes or ethyl acrylate as the source of arylation or olefination, respectively
Substrate-Controlled Synthesis of SpirocycloÂpropylÂpyrazolones and Bicyclic 4,5-Dihydropyrazoles from 1,2-Diaza-1,3-dienes with Sulfur Ylides
Substrate-controlled reactions have
been developed for the synthesis
of spirocycloÂpropylÂpyrazolones and bicyclic 4,5-dihydropyrazoles
from 1,2-diaza-1,3-dienes and sulfur ylides. These protocols were
carried out under mild reaction conditions without any additives in
generally moderate to good yields. Plausible mechanisms for the transformations
were proposed
Tuning the Annulation Reactivity of Vinyl Azides and Carbazates: A Divergent Synthesis of Aza-pyrimidinones and Imidazoles
A divergent
cascade annulation has been developed using readily
available vinyl azides and carbazates with a wide range of substituents.
Vinyl azides were successfully applied as bifunctional partners to
prepare aza-pyrimidinones via 6-ring closure with carbazates as well
as to construct polyfunctionalized imidazoles via 5-ring closure with <i>N</i>-substituted carbazates. The aza-heterocycles were obtained
with high levels of chemoselectivity and excellent yields
One-Pot Three-Component Approach to the Synthesis of Polyfunctional Pyrazoles
A simple, multicomponent, and straightforward reaction of vinyl azide, aldehyde, and tosylhydrazine affords the construction of 3,4,5-trisubstituted 1<i>H</i>-pyrazoles regioselectively in the presence of base with moderate to excellent yields. A range of functionality could be tolerated in this methodology, and a possible mechanism is proposed
Direct Access to 3‑Thioether-Substituted Dihydrofuro[2,3‑<i>b</i>]benzofurans via Tandem Reactions of Sulfur Ylides and 2‑Nitrobenzofurans
The
synthesis of 3-thioether-substituted dihydrofuro[2,3-b]benzofurans involving the [3 + 2] coupling of sulfur ylides
with 2-nitrobenzofurans has been realized in moderate to good yields
under mild conditions without any precious catalysts or additives.
It is worth mentioning that the reutilization of the departed nitro-anion
in the reaction process facilitates this new chemical transformation
and presents a manner of high atom economy to provide products with
a complex structure
Synthesis of Pyrimidopyrrolopyridazines via a Tandem Reaction of Heterocyclic Ketene Aminals with 1,2-Diaza-1,3-dienes
A tandem
reaction of heterocyclic ketene aminals and 1,2-diaza-1,3-dienes
was developed for the expedient synthesis of pyrimidopyrrolopyridazine
derivatives. This process involved an intramolecular conjugate addition
followed by CuCl<sub>2</sub>-catalyzed hydrazone formation
A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles
Gatekeeper
T790 M mutation in EGFR is the most prevalent factor
underlying acquired resistance. Acrylamide-bearing quinazoline derivatives
are powerful irreversible inhibitors for overcoming resistance. Nevertheless,
concerns about the risk of nonspecific covalent modification have
motivated the development of novel cysteine-targeting inhibitors.
In this paper, we demonstrate that fluoro-substituted olefins can
be tuned to alter Michael addition reactivity. Incorporation of these
olefins into the quinazoline templates produced potent EGFR inhibitors
with improved safety and pharmacokinetic properties. A lead compound <b>5a</b> was validated against EGFR<sup>WT</sup>, EGFR<sup>T790M</sup> as well as A431 and H1975 cancer cell lines. Additionally, compound <b>5a</b> displayed a weaker inhibition against the EGFR-independent
cancer cell line SW620 when compared with afatinib. Oral administration
of <b>5a</b> at a dose of 30 mg/kg induced tumor regression
in a murine-EGFR<sup>L858R/T790M</sup> driven H1975 xenograft model.
Also, <b>5a</b> exhibited improved oral bioavailability and
safety as well as favorable tissue distribution properties and enhanced
brain uptake. These findings provide the basis of a promising strategy
toward the treatment of NSCLC patients with drug resistance