The impact of binding site waters on the activity/selectivity trade-off of Janus kinase 2 (JAK2) inhibitors
Structure based optimization of B39, an indazole-based low micromolar JAK2 virtual screening hit is reported. Analysing the effect of certain modifications on the activity and selectivity of the analogues suggested that these parameters are influenced by
Egyed, Attila,Bajusz, Dávid,Keser?, Gy?rgy M.
p. 1497 - 1508
(2019/03/05)
1,6 - SUBSTITUTED (3R,6R) -3- (2,3-DIHYDRO-1H-INDEN-2-YL)-2,5-PIPERAZINEDIONE DERIVATIVES AS OXYTOCIN RECEPTOR ANTAGONISTS FOR THE TREATMENT OF PRE-TERM LABOUR, DYSMENORRHEA AND ENDOMETRIOSIS
The present invention relates to compound S of Formula (I).
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Page/Page column 58-59
(2008/06/13)
Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors
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.
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)
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