Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.

Malaria remains a serious global health challenge, yet treatment and control programs are threatened by drug resistance. Dihydroorotate dehydrogenase (DHODH) was clinically validated as a target for treatment and prevention of malaria through human studies with DSM265, but currently no drugs against this target are in clinical use. We used structure-based computational tools including free energy perturbation (FEP+) to discover highly ligand efficient, potent, and selective pyrazole-based DHODH inhibitors through a scaffold hop from a pyrrole-based series.

Copper-catalyzed C-H ethoxycarbonyldifluoromethylation of imidazoheterocycles.

A regioselective copper-catalyzed ethoxycarbonyl-difluoromethylation of imidazo[1,2-a]pyridines has been developed through sp(2) C-H bond functionalization with BrCF2CO2Et under ambient air. A series of ethoxycarbonyldifluoromethylated imidazo[1,2-a]pyridines with broad functionalities have been synthesized. This methodology is also applicable to imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole.

Diversified Synthesis of Furans by Coupling between Enols/1,3-Dicarbonyl Compounds and Nitroolefins: Direct Access to Dioxa[5]helicenes.

A versatile method for the diversified synthesis of furans and arenofurans has been developed that proceeds through K2CO3-promoted cyclization between enols/1,3-dicarbonyl compounds and nitroolefins at reflux in EtOH. This facile method has been successfully employed in the synthesis of benzotrifuran derivatives, which are useful hole-transporting materials. This procedure also provides direct access to dioxa[5]helicenes.

Regioselective synthesis of nitrosoimidazoheterocycles using tert-butyl nitrite.

A simple and practical method has been developed for the regioselective nitrosylation of imidazopyridines via C(sp(2))-H bond functionalization using tert-butyl nitrite under mild reaction conditions in a short time. A library of 3-nitrosoimidazopyridines with broad functionalities was synthesized in near quantitative yields. The present protocol is also applicable to imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole.

Synthesis, structure and spectroscopic properties of Re(I) complexes incorporating 5-arylazo-8-hydroxyquinoline: a density functional theory/time-dependent density functional theory investigation.

Dinuclear rhenium(I) complexes having a fac-[Re(CO)3](+) moiety of general formula fac-[Re2(CO)6(hq)2] have been synthesized in excellent yield by reacting [Re(CO)5Cl] with Hhq in a ratio of 1 : 1 in toluene in an argon atmosphere. Here hq(-) is the deprotonated form of 5-phenylazo-8-hydroxyquinoline (Hhq(1)), 5-(2-naphthylazo)-8-hydroxyquinoline (Hhq(2)) and 5-(2-fluorineazo)-8-hydroxyquinoline (Hhq(3)). The reaction of synthesized dinuclear complexes with imidazole (Im) and N-methylimidazole (N-MeIm) in dry dichloromethane under argon atmosphere afforded the mononuclear complexes of general formula fac-[Re(CO)3(hq)(Im)] and fac-[Re(CO)3(hq)(N-MeIm)] respectively in high yield.

A novel copper(II) complex as a nitric oxide turn-on fluorosensor: intracellular applications and DFT calculation.

We report, herein, the development of an easily synthesizable novel dansyl-based turn-on NO sensor L2. The UV-Vis titration data of L2 with Cu(2+) display a gradual increase in absorbance at 418 nm with [Cu(2+)], which were analyzed by using a non-linear least-squares computer-fit program yielding K = (1.16 ± 0.

Synthesis, structure and spectral properties of O,N,N coordinating ligands and their neutral Zn(ii) complexes: a combined experimental and theoretical study.

Mononuclear Zn(ii) complexes with the general formula [Zn(L)2] have been synthesized in good yields by reacting Zn(OAc)2 with HL in a ratio of 1 : 2 in methanol solvent. Here L is the deprotonated form of 6-[(quinolin-8-ylamino)methylene]cyclohexa-2,4-dienone (HL(1)), 4-chloro-6-[(quinolin-8-ylamino)methylene]cyclohexa-2,4-dienone (HL(2)), 4-methyl-6-[(quinolin-8-ylamino)methylene]cyclohexa-2,4-dienone (HL(3)), 2,4-dimethyl-6-[(quinolin-8-ylamino) methylene]cyclohexa-2,4-dienone (HL(4)), 2-methoxy-6-[(quinolin-8-ylamino) methylene]cyclohexa-2,4-dienone (HL(5)). The electronic structures and photophysical properties of the ligands were calculated by DFT and TDDFT methods.

Mononuclear and dinuclear Re(I) complexes incorporating 1-(2-pyridylazo)-2-naphthol: synthesis, structure, spectral, DFT and TDDFT studies.

The Re(I) complexes [Re(HPAN)(CO)(3)Cl], 1, and [Re(2)(PAN)(2)(CO)(6)]·C(6)H(12), 2·C(6)H(12), have been prepared by reacting [Re(CO)(5)Cl] with HPAN. Here (PAN)(-) is the deprotonated form of 1-(2-pyridylazo)-2-naphthol. A subsequent reaction of [Re(HPAN)(CO)(3)(CF(3)SO(3))] with a chelating diphosphine ligand generates [Re(PAN)(CO)(P-P)]·CH(2)Cl(2), 3·CH(2)Cl(2).