We previously reported the design
of spirooxindoles with two identical
substituents at the carbon-2 of the pyrrolidine core as potent MDM2
inhibitors. In this paper we describe an extensive structure–activity
relationship study of this class of MDM2 inhibitors, which led to
the discovery of 60 (AA-115/APG-115). Compound 60 has a very high affinity to MDM2 (Ki < 1 nM), potent cellular activity, and an excellent oral
pharmacokinetic profile. Compound 60 is capable of achieving
complete and long-lasting tumor regression in vivo and is currently
in phase I clinical trials for cancer treatment.
A series of novel pyrazole oxime derivatives containing a 2-chloro-5-thiazolyl moiety were synthesized. Their structures were confirmed by (1)H NMR, (13)C NMR, and elemental analysis. The preliminary bioassays showed that all of the title compounds had low acaricidal activity against Tetranychus cinnabarinus . However, most of them exhibited excellent insecticidal activity against Aphis medicagini at the dosage of 0.5 mg/mL, and some compounds still showed good insecticidal activity against A. medicagini even at the dosage of 0.2 mg/mL. Meanwhile, some title compounds displayed fungicidal and plant growth regulatory activities.
Novel TiO 2 /Bi 2 MoO 6 heterostructures with TiO 2 particles loaded on a Bi 2 MoO 6 sheet were fabricated by a simple solvothermal process. A series of characterization techniques such as SEM, TEM, XRD, XPS, UV−vis DRS, and electrochemical impedance approach were used to study the physicochemical properties of the as-prepared materials. The TiO 2 /Bi 2 MoO 6 composites were used for partial oxidation of aromatic alkanes into benzaldehyde and its derivatives using O 2 as an oxidant under the irradiation of visible light. At a TiO 2 -to-Bi 2 MoO 6 molar ratio of 0.10, the composite exhibits excellent performance with benzaldehyde production rate being 1036.8 μmol•g −1 •h −1 . The outstanding performance is ascribed to enhanced separation of charge carriers by loading TiO 2 nanoparticles. The as-prepared composites are reusable photocatalysts for partial oxidation of aromatic alkanes under ambient conditions.
A new and stereoselective synthetic approach to spirooxindole 4H-pran-2-one derivatives with three contiguous stereogenic centers has been developed via an NHC-catalyzed three-component domino reaction of alkynyl aldehydes with oxindoles. The reaction proceeds smoothly in good yields with good to high diastereoselectivities. These novel heterocyclic spirooxindoles may provide promising candidates for drug discovery. Additionally, a possible mechanism for the entire reaction sequence is proposed.
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