449758-08-1Relevant academic research and scientific papers
Identification of a series of 1,3,4-trisubstituted pyrazoles as novel hepatitis C virus entry inhibitors
Hwang, Jong Yeon,Kim, Hee-Young,Park, Dong-Sik,Choi, Jihyun,Baek, Sung Min,Kim, Keumhyun,Kim, Soohyun,Seong, Sikwang,Choi, Inhee,Lee, Hong-Gun,Windisch, Marc Peter,Lee, Jinhwa
, p. 6467 - 6473 (2013/11/19)
In this report we describe the identification of novel pyrazole analogs as potent hepatitis C virus (HCV) entry inhibitor. The pyrazoles were identified by our phenotypic high-throughput screening using infectious HCV. A series of pyrazole derivatives was synthesized and evaluated for inhibitory activity against HCV in the infectious cell culture system. Through evaluation of selected compounds we observed that the pyrazoles did not interfere with HCV RNA replication but with viral entry as shown by experiments with HCV replicons and HCV pseudo particles, respectively.
Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors
Young, Mary Beth,Barrow, James C.,Glass, Kristen L.,Lundell, George F.,Newton, Christina L.,Pellicore, Janetta M.,Rittle, Kenneth E.,Selnick, Harold G.,Stauffer, Kenneth J.,Vacca, Joseph P.,Williams, Peter D.,Bohn, Dennis,Clayton, Franklin C.,Cook, Jacquelynn J.,Krueger, Julie A.,Kuo, Lawrence C.,Lewis, S. Dale,Lucas, Bobby J.,McMasters, Daniel R.,Miller-Stein, Cynthia,Pietrak, Beth L.,Wallace, Audrey A.,White, Rebecca B.,Wong, Bradley,Yan, Youwei,Nantermet, Philippe G.
, p. 2995 - 3008 (2007/10/03)
In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P1 region. Various benzylamines were coupled to a pyridine/pyrazinone P2-P 3 template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin Ki of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P1 aryl heterocycles with a variety of P2-P3 groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P1 will allow for more diversification in the P 2-P3 region to ultimately address additional pharmacological concerns.
Thrombin inhibitors
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, (2008/06/13)
Compounds of the invention are useful in inhibiting thrombin and treating blood coagulation and cardiovascular disorders and have the following structure: wherein R3 is hydrogen or halogen, and u is N or CH.
