283153-85-5

Malignant gliomas are the most common brain tumors, with generally dismal prognosis, early clinical deterioration and high mortality. Recently, 2-aminoquinoline scaffold derivatives have shown pronounced activity in central nervous system disorders. We herein reported a series of 2-aminoquinoline-3-carboxamides as novel non-alkylator anti-glioblastoma agents. The synthesized compounds showed comparable activity to cisplatin against glioblastoma cell line U87 MG in vitro. Among them, we found that 6a displayed good inhibitory activity against A172 and U118 MG glioblastoma cell lines and induced cell cycle arrest in the G2/M phase and apoptosis in U87 MG by flow cytometry analysis. Additionally, 6a displayed low cytotoxicity to several normal human cell lines. In silico study showed 6a had promising physicochemical properties and was predicted to cross the blood–brain barrier. Moreover, preliminary structure–activity relationships are also investigated, shedding light on further modifications towards more potent agents on this series of compounds. Our results suggest this compound has a promising potential as an anti-glioblastoma agent with a differential effect between tumor and non-malignant cells.

Chitinases are the glycosyl hydrolase for catalyzing the degradation of chitin and play an indispensable role in bacterial pathogenesis, fungal cell wall remodeling, and insect molting. Thus, chitinases are attractive targets for therapeutic drugs and pes

A variety of transition metal complexes involving picolylcyanoacetamides (pica=NCCH2CONH-R; R=2-picolyl-(2pica), 3-picolyl-(3pica), 4-picolyl-(4pica)) and thiocyanate have been synthesised and their solid-state structures have been determined. The complexes were all obtained from reactions between the corresponding metals salts and pica ligands with sodium thiocyanate under ambient conditions. Both 3pica and 4pica coordinate to the metal solely through the nitrogen atom of the picolyl group and form discrete tetrahedral [M(NCS)2(pica)2] (3pica; M=Mn, Zn; 4pica; M=Co) and octahedral [M(NCS)2(3pica)4] (M=Co, Fe, Ni) complexes. In addition, one-dimensional N,S-thiocyanate-bridged coordination polymers poly-[M(NCS)2(pica)2] (3pica; M=Cd; 4pica; M=Co, Cd) were obtained. The ligand 2pica gave the discrete octahedral complexes [Co(NCS)2(2pica)2] and [Cd(NO3)2(2pica)2] in which 2pica chelates in a bidentate fashion through its picolyl and carbonyl groups. Magnetic susceptibility measurements on the cobalt(ii) complexes were performed and showed short-range antiferromagnetic coupling for the [Co(NCS)2(4pica)2]n 1D polymer.

The neonatal Fc receptor, FcRn, prolongs the half-life of IgG in the serum and represents a potential therapeutic target for the treatment of autoimmune disease. Small molecules that block the protein-protein interactions of human IgG-human FcRn may lower pathogenic autoantibodies and provide effective treatment. A novel class of quinoxalines has been discovered as antagonists of the IgG:FcRn protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen.

Cyanoacetic acid derivatives are the starting materials for a plethora of multicomponent reaction (MCR) scaffolds. Herein, we describe scope of a valuable general protocol for the synthesis of arrays of 2-aminoquinoline-3-carboxamides from cyanoacetamides and 2-aminobenzaldehydes or heterocyclic derivatives via a Friedlaender reaction variation. In many cases, the reactions involve a very convenient work up by simple precipitation and filtration. More than 40 new products are described. We foresee our protocol and the resulting derivatives becoming very valuable to greatly expanding the scaffold space of cyanoacetamide derivatives.

Compounds, compositions and methods for modulating the activity of nuclear receptors are provided. In particular, heterocyclic compounds are provided for modulating the activity of nuclear receptors, including liver X receptor (LXR) and orphan nuclear receptors. In certain embodiments, the compounds are N-substituted pyridones.