55218-70-7Relevant academic research and scientific papers
Inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies
Deng, Lisheng,Diao, Jiasheng,Chen, Pinhong,Pujari, Venugopal,Yao, Yuan,Cheng, Gang,Crick, Dean C.,Prasad, B. V. Venkataram,Song, Yongcheng
experimental part, p. 4721 - 4734 (2011/09/19)
1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.
2-pyridine Derivatives: New Antiinflammatory Agents
Haviv, Fortuna,DeNet, Robert W.,Michaels, Raymond J.,Ratajczyk, James D.,Carter, George W.,Young, Patrick R.
, p. 218 - 222 (2007/10/02)
2-pyridine derivatives (1a-e) inhibited the dermal reverse passive Arthus reaction (RPAR) in the rat.In the same model, indomethacin was inactive, and hydrocortisone was active.Compounds 1a-d also significantly reduced exudate volume and white blood cell accumulation in the pleural RPAR.This pattern of activity was similar to that of hydrocortisone and different from that of indomethacin.
