Akt, a serine/threonine protein kinase as a viral oncogene, is a critical regulator of PI3K-mediated cell proliferation and survival. On translocation, Akt is phosphorylated and activated, ultimately resulting in stimulation of cell growth and survival. As a part of our program toward the novel Akt1 inhibitors with potent activity over PI3K signaling pathway, we found primary hit compound 2 with an IC50 value of 620μM from protein kinase focused library. Based on the structural features of 2, new 1,3,4-thiadiazole derivatives were designed by the introduction of aromatic and heteroaromatic moieties onto thiadiazole nucleus. In this work, a series of 1,3,4-thiadiazole derivatives 1a-1 were synthesized and evaluated for Akt1 inhibitory activity.

Based on the Benzoflex (Vesicol Chemical Co.) as PVC plasticizer substituents for Di-n-octyl phthalate (DOP), a series of new aromatic carboxylic acid ester compounds were designed as plasticizers, synthesized, and screened for the endocrine disrupting activity. 2-Hydroxybenzoic acid (1) and 2-methoxybenzoic acid (2) as the commercially available starting materials were reacted with diethylene glycol (3) in the presence of p-toluenesulfonic acid using Dean-Stark column to give diethylene glycol di-(2-hydroxy)benzoate (4, KH01) and diethylene glycol di-(2-methoxy)benzoate (5, KH02), respectively. And diethylene glycol di-(3-pyridinyl) ester (7, KH03) and dipropylene glycol di-(3-pyridinyl) ester (9, KH04) were obtained in high yields by treatment of nicotinoyl chloride (6) with diethylene glycol (3) and dipropylene glycol (8) in the presence of triethylamine as a base. To determine the estrogenic disrupting effect of new synthetic phthalate analogues, E-screen assay method was used. Of these compounds, 4 (KH01) was found to be compound without endocrine disrupting effect.