Gyochang Keum

A facile synthesis of N-carbamoylmethyl- α -aminobutyrolactones by the Ugi multicomponent condensation reaction

Abstract A new method of various N-carbamoylmethyl-α-amino-butyrolactones4 utilizing the intramolecular Ugi five-center-three-component condensation reaction starting from l -homoserine was developed.

Indium mediated pinacol coupling reaction of aromatic aldehydes in aqueous media

Abstract The carbon-carbon bond formation reaction of aromatic carbonyl compounds was performed with indium in neutral aqueous media using sonication affording the corresponding diols in moderate to good yields.

A new peptide bond surrogate: 2-isoxazoline in pseudodipeptide chemistry

Abstract The 2-isoxazoline ring has been incorporated as a new peptide bond surrogate into pseudodipeptide. An easy and versatile general method for the preparation of pseudodipeptides is described.

Discovery and development of heat shock protein 90 inhibitors as anticancer agents: a review of patented potent geldanamycin derivatives

Introduction: There has been research on anticancer strategies which focus on disrupting a single malignant protein. One of the strategies is the inhibition of one protein, heat shock protein 90 (Hsp90). There are many reasons why Hsp90 protein is targeted by anticancer agents: maintenance of cellular homeostasis in organisms involves Hsp90 and its client proteins; moreover, Hsp90 complex is involved in regulating several signal transduction pathways and plays an important role in the maturation of lots of tumor-promoting client proteins. Geldanamycin (GM), the first benzoquinone ansamycin, has shown anticancer activity by binding to Hsp90. Currently, several GM derivatives such as 17-AAG, 17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin, IPI-493, and IPI-504 are being progressively developed toward clinical application. Areas covered: Several research groups have studied GM and its derivatives to develop novel and potent Hsp90 inhibitors for the treatment of cancer. The crystal structure of Hsp90 was utilized to undergo structural optimization of GM derivatives. A wide variety of structural modifications were performed and some of the derivatives are now in clinical studies. The aim of this review was to summarize and analyze the structure-activity relationships of GM derivatives and the focus is on patented novel and pharmaceutically efficacious derivatives published from 1971 to 2012. Expert opinion: Hsp90 inhibitors offer an effective therapeutic approach for treatment of cancer. To date, the clinical results of 17-AAG, IPI-493, and IPI-504 suggest that these GM derivatives could be used either alone or in combination with other marketed medications for the treatment of cancer patients. As there are not any marketed Hsp90 inhibitors, inhibiting Hsp90 chaperone function remains as a promising strategy that still requires further research.

An efficient synthesis of 2,5-diketopiperazine derivatives by the Ugi four-center three-component reaction

A facile synthetic approach to 2,5-diketopiperazines 4 by the Ugi four-center three-component reaction using commercially available dipeptides as a bifunctional component, aldehydes, and isocyanides was described.

Indium-mediated monoallylation of carbonyl compounds with allylic chlorides and bisallylation of 2-pyridyl carboxylates with allylic halides in aqueous media

Abstract Allylic chlorides are efficient reagents in the indium-mediated Barbier-type allylation reaction with various aldehydes and ketones in pure water under sonication or in a 1:1 mixture of H 2 O and t-BuOH. Also indium is effective in bisallylation reactions of the 2-pyridyl esters with allyl halides in pure water.

A new direct allylation of the aromatic compounds with allylic chlorides catalyzed by indium metal

Abstract A new method of the direct allylation reaction for the aromatic compounds with allylic chlorides using a catalytic amount of indium in the presence of CaCO 3 4 A molecular sieves was developed.

A facile synthesis of 7-amino-3-desacetoxycephalosporanic acid derivatives by indium-mediated reduction of 3-iodomethylcephems in aqueous media

Abstract An efficient reductive conversion of 3-iodomethylcephalosporin and 3-acetoxymethylcephalosporin derivatives mediated by indium into the corresponding 3-methylcephems and 3-methylenecephams in moderate to good yields has been developed in an aqueous system. 3-Methylenecephams are converted into the corresponding 3-methylcephems under previously reported basic conditions quantitatively.

Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease

In Parkinsons disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinsons disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinsons disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure-activity relationship study revealed that the piperidino group was the best choice for the R(1) amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5nM in IC50 values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound 1n with the thiazolopyridine core structure showed the most potent activity with the IC50 value of 26.5nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives.

Synthesis and biological evaluation of 1-(isoxazol-5-ylmethylaminoethyl)-4-phenyl tetrahydropyridine and piperidine derivatives as potent T-type calcium channel blockers with antinociceptive effect in a neuropathic pain model.

New tetrahydropyridinyl and piperidinyl ethylamine derivatives were designed with hypothetical mapping on pharmacophore model generated from ligand-based virtual screening. The designed compounds were synthesized, and their inhibitory activities on T-type calcium channel were assayed using FDSS and patch-clamp assay. Among them, compounds 7b and 10b showed potent T-type calcium current blocking activity against Ca(v)3.1 (α(1G)) and Ca(v)3.2 (α(1H)) channel simultaneously. With hERG and pharmacokinetics studies, compounds 7b and 10b were evaluated for the antinociceptive effect on rat model of neuropathic pain. They were significantly effective in decreasing the pain responses to mechanical and cold allodynia induced by spinal nerve ligation. These results suggest that modulation of α(1G) and α(1H) subtype T-type calcium channels may provide a promising approach for the treatment of neuropathic pain.