- A convenient synthesis of 2-acyl benzothiazoles/thiazoles from benzothiazole/thiazole and N,N'-carbonyldiimidazole activated carboxylic acids
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A convenient and efficient strategy for the synthesis of 2-acyl benzothiazoles/thiazoles has been developed. The treatment of benzothiazole/thiazole with allylic Grignard reagents readily generates the corresponding 2-Grignard reagents, which is followed by a reaction with N,N'-carbonyldiimidazole activated carboxylic acids to afford various 2-acyl benzothiazoles/thiazoles products. The synthetic method is applicable to a wide array of carboxylic acids and allows easy access to 2-acyl benzothiazoles/thiazoles with considerable yields under mild reaction conditions.
- Huang, Tonghui,Wu, Xin,Yu, Yongbo,An, Lin,Yin, Xiaoxing
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supporting information
p. 1667 - 1670
(2019/06/04)
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- ANTIINFLAMMATORY AND ANTITUMOR 2-OXOTHIAZOLES AND 2-OXOTHIOPHENES COMPOUNDS
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A compound of formula (I) wherein X is O, C O or S; Y is N or CH; R2 and R4 are each independently H, -(CH2)pCOOH, -(CH2)pCON(R5)2 or - (CH2)pCOOC 1-6alkyI; or R2 and R4 together form a 6-membered phenyl ring fused to the five membered ring; each R1 is independently selected from H, halo (e.g. fluoro or chloro), C6-10aryl, C7-12arylalkyl, C2-12alkenyl; OC1-2 alkyl, OC2-12 aikenyl or a C1-12 alkyl group; each R5 is H or C1-6 alkyl; each p is 0 to 3; n is 1 to 4; or a salt, ester, solvate, N-oxide, or prodrug thereof, e.g. a salt thereof.
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- Inhibition of group IVA cytosolic phospholipase A2by thiazolyl ketones in vitro, ex vivo, and in vivo
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Group IVA cytosolic phospholipase A2(GIVA cPLA2) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA2, exhibiting an XI(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50value of 0.6 μM. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE2levels.
- Kokotos, George,Feuerherm, Astrid J.,Barbayianni, Efrosini,Shah, Ishita,S?ther, Mari,Magrioti, Victoria,Nguyen, Thuy,Constantinou-Kokotou, Violetta,Dennis, Edward A.,Johansen, Berit
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p. 7523 - 7535
(2015/01/08)
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