148834-04-2Relevant articles and documents
NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF
-
Page/Page column 24, (2011/11/12)
The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.
Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors
Wu, Ying,Tai, Hsin-Hsiung,Cho, Hoon
experimental part, p. 1428 - 1433 (2010/05/02)
Prostaglandins have a short life in vivo because they are metabolized rapidly by oxidation to 15-ketoprostaglandins catalyzed by a cytosolic enzyme known as NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, CT-8, a thiazolidinedione analogue, was found to be a potent inhibitor of 15-PGDH. Structure-activity analysis indicated that the N-methylation of thiazolidine-2,4-dione, CT-8, abolished the inhibitory activity, whereas the introduction of an ethyl hydroxyl group at amine in CT-8 still had a good inhibitory effect. Based on the structures of the thiazolidinediones analogues and inhibitory activity, a range of benzylidene thiazolidinedione derivatives were synthesized with different substituents on the phenyl ring and their inhibitory activity was evaluated. Replacement of the cyclohexylethyl group of CT-8 with the hetero five-member ring increased the inhibitory potency. However, replacement of the cyclohexylethyl group with a hetero six-member ring decreased the inhibitory potency significantly. It was found that compound 2 (5-(4-(2-(thiophen-2-yl)ethoxy)benzylidene)thiazolidine-2,4-dione) was the most potent inhibitor that was effective in the nanomolar range.
Heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic acids as leukotriene biosynthesis inhibitors
Kolasa, Teodozyj,Gunn, David E.,Bhatia, Pramila,Woods, Keith W.,Gane, Todd,Stewart, Andrew O.,Bouska, Jennifer B.,Harris, Richard R.,Hulkower, Keren I.,Malo, Peter E.,Bell, Randy L.,Carter, George W.,Brooks, Clint D. W.
, p. 690 - 705 (2007/10/03)
A novel series of heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic acids was studied as leukotriene biosynthesis inhibitors. A hypothesis of structure-activity optimization by insertion of an oxime moiety was investigated using REV-5901 as a starting point. A systematic structure- activity optimization showed that the spatial arrangement and stereochemistry of the oxime insertion unit proved to be important for inhibitory activity. The promising lead, S-(E)-11, inhibited LTB4 biosynthesis in the intact human neutrophil with IC50 of 8 nM and had superior oral activity in vivo, in a rat pleurisy model (ED50 = 0.14 mg/kg) and rat anaphylaxis model (ED50 = 0.13 mg/kg). In a model of lung inflammation, S-(E)-11 blocked LTE4 biosynthesis (ED50 of 0.1 mg/kg) and eosinophil influx (ED50 of 0.2 mg/kg). S-(E)-11 (A-93178) was selected for further preclinical evaluation.
