180002-10-2Relevant academic research and scientific papers
An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials
?eren, Mario,Aithani, Laksh,Anderson, Mark,Cardoso-Silva, Jonathan,Cincilla, Giovanni,Conduit, Gareth J.,Galushka, Mykola,Guan, Davy,Hallyburton, Irene,Irwin, Benedict W. J.,Kirk, Kiaran,Lehane, Adele M.,Lindblom, Julia C. R.,Lui, Raymond,Matthews, Slade,McCulloch, James,Motion, Alice,Ng, Ho Leung,Robertson, Murray N.,Spadavecchio, Vito,Tatsis, Vasileios A.,Todd, Matthew H.,Tse, Edwin G.,Van Hoorn, Willem P.,Wade, Alexander D.,Whitehead, Thomas M.,Willis, Paul
supporting information, p. 16450 - 16463 (2021/11/24)
The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The structure of PfATP4 has not been determined. Here, we des
QUINOLONE DERIVATIVES AS FIBROBLAST GROWTH FACTOR RECEPTOR INHIBITORS
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Page/Page column 78, (2016/12/16)
Compounds of formula (I) that are Fibroblast Growth Factor Inhibitors (FGFR) and are therefore useful for the treatment of diseases treatable by inhibition of FGFR are disclosed. Also disclosed are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
QUINOLONE DERIVATIVES AS FIBROBLAST GROWTH FACTOR INHIBITORS
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Page/Page column 55; 56, (2014/12/09)
Compounds of formula (Ι') that are Fibroblast Growth Factor Inhibitors (FGFR) and are therefore useful for the treatment of diseases treatable by inhibition of FGFR are disclosed. Also disclosed are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
N-phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: Structure-activity studies and demonstration of in vivo activity
Collins, Jon L.,Shearer, Barry G.,Oplinger, Jeffrey A.,Lee, Shuliang,Garvey, Edward P.,Salter, Mark,Duffy, Claire,Burnette, Thimysta C.,Furfine, Eric S.
, p. 2858 - 2871 (2007/10/03)
Selective inhibition of the neuronal isoform of nitric oxide synthase (NOS) compared to the endothelial and inducible isoforms may be required for treatment of neurological disorders caused by excessive production of nitric oxide. Recently, we described N-(3-(aminomethyl)benzyl)acetamidine (13) as a slow, tight-binding inhibitor, highly selective for human inducible nitric oxide synthase (iNOS). Removal of a single methylene bridge between the amidine nitrogen and phenyl ring to give N-(3- (aminomethyl)phenyl)acetamidine (14) dramatically altered the selectivity to give a neuronal selective nitric oxide synthase (nNOS) inhibitor. Part of this large shift in selectivity was due to 14 being a rapidly reversible inhibitor of iNOS in contrast to the essentially irreversible inhibition of iNOS observed with 13. Structure-activity studies revealed that a basic amine functionality tethered to an aromatic ring and a sterically compact amidine are key pharmacophores for this class of NOS inhibitors. Maximal nNOS inhibition potency was achieved with N-(3-(aminomethyl)phenyl)-2- furanylamidine (77) (K(i-nNOS) = 0.006 μM; K(i-eNOS) = 0.35 μM; K(i-iNOS) = 0.16 μM). Finally, α-fluoro-N-(3-(aminomethyl)phenyl)acetamidine (74) (K(i- nNOS) = 0.011 μM; K(i-eNOS) = 1.1 μM; K(i-iNOS) = 0.48 μM) had excellent brain penetration and inhibited nNOS in a rat brain slice assay as well as in the rat brain (cerebellum) in vivo. Thus, N-phenylamidines should be useful in validating the role of nNOS in neurological disorders.
