Sung Gyu Kim

Synthesis and biological evaluation of homopiperazine derivatives with beta-aminoacyl group as dipeptidyl peptidase IV inhibitors

Compounds with homopiperazine skeleton are designed to find a potent DPP-IV inhibitor without inhibiting CYP. Thus a series of beta-aminoacyl-containing homopiperazine derivatives was synthesized and evaluated. Compounds with acid moiety were found to be potent inhibitors of DPP-IV without inhibiting CYP 3A4. More specifically, compound 7m showed nanomolar activity with no inhibition towards five subtypes of CYPs, was considered as a prototype for further derivatization. Based on its X-ray co-crystal structure with human DPP-IV, we identified compounds 7s and 7t which showed good in vitro activity, no CYP inhibition, and good selectivity.

Synthesis and biological evaluation of pyrazoline analogues with β-amino acyl group as dipeptidyl peptidase IV inhibitors

A series of pyrazoline derivatives with beta-amino acyl group were synthesized and evaluated for their ability to inhibit dipeptidyl peptidase IV. Several pyrazoline derivatives exhibited submicromolar inhibitory activities against DPP-IV. X-ray co-crystal structure of initial hit compound 1h was determined. Among this series, carboxylic acid substituted pyrazoline derivative 2u was the most active and greatly decreased the inhibitory activity toward CYP3A4 enzyme.

Biochemical and Pharmacological Characteristics of 3-Butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a New Proton-pump Inhibitor, in Rabbit Gastric Microsomes and in Rats

We have investigated the properties of the newly synthesized proton‐pump inhibitor, 3‐butyryl‐8‐methoxy‐4‐[(2‐thiophenyl)amino]quinoline (YJA20379–6), on gastric mucosal proton‐pump (H+/K+‐ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats.

Biochemical and pharmacological properties of a new proton pump inhibitor, 2-amino-4,5-dihydropyrido[1,2-a]thiazolo [5,4-g] benzimidazole (YJA20379-5)

This study was designed to determine biochemical and pharmacological properties of a newly synthesized benzimidazole derivative, 2-amino-4,5-dihydropyrido [1,2-a] thiazolo [5,4-g] benzimidazole (YJA20379-5)in vitro andin vivo. In the leaky membrane vesicles of pig gastric mucosa, YJA20379-5 inhibited the K+-stimulated H+,K+-ATPase activity in a concentration- and time-dependent manner, with IC50 values being 43 μM and 31 μM at pH 6.4 and 7.4, respectively. YJA20379-5, given intraduodenally, had a potent inhibitory effect on the gastric acid secretion in pylorus-ligated rats. The ED50 value for acid secretion was 15.4 mg/kg. YJA20379-5, administered orally, also suppressed gastric damages induced by water-immersion stress, indomethacin and ethanol, and duodenal damage induced by mepirizole in rats; the ED50 values were 17.6, 4.7, 3.0 and 18.7 mg/kg, respectively. Furthermore, repeated oral administration of YJA20379-5 accelerated the spontaneous healing of acetic acid-induced gastric ulcers in rats. It is concluded that the antisecretory activity of YJA20379-5 appears to be associated with inhibition of H+,K+-ATPase, while its antigastric and antiduodenal lesion activities are primarily related to the antisecretory effect.