1189770-53-3Relevant academic research and scientific papers
Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties
Soth, Michael J.,Le, Kang,Di Francesco, Maria Emilia,Hamilton, Matthew M.,Liu, Gang,Burke, Jason P.,Carroll, Chris L.,Kovacs, Jeffrey J.,Bardenhagen, Jennifer P.,Bristow, Christopher A.,Cardozo, Mario,Czako, Barbara,De Stanchina, Elisa,Feng, Ningping,Garvey, Jill R.,Gay, Jason P.,Do, Mary K. Geck,Greer, Jennifer,Han, Michelle,Harris, Angela,Herrera, Zachary,Huang, Sha,Giuliani, Virginia,Jiang, Yongying,Johnson, Sarah B.,Johnson, Troy A.,Kang, Zhijun,Leonard, Paul G.,Liu, Zhen,McAfoos, Timothy,Miller, Meredith,Morlacchi, Pietro,Mullinax, Robert A.,Palmer, Wylie S.,Pang, Jihai,Rogers, Norma,Rudin, Charles M.,Shepard, Hannah E.,Spencer, Nakia D.,Theroff, Jay,Wu, Qi,Xu, Alan,Yau, Ju Anne,Draetta, Giulio,Toniatti, Carlo,Heffernan, Timothy P.,Jones, Philip
, p. 12957 - 12977 (2020/11/13)
Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.
1-HETEROCYCLYL-1,5-DIHYDRO-PYRAZOLO[3,4-D] PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A MODULATORS
-
, (2009/10/30)
The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, Formula (I) with Hc is a mono-, bi- or tricyclic heterocyclyl group, the ring members of which are carbon atoms and at least 1, preferably 1, 2 or 3, heteroatom(s), which are selected from the group of nitrogen, oxygen and sulphur, which is in the form of -S(O)r - with r being 0, 1 or 2, and - said heterocyclyl group is or comprises 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member and - said heterocyclyl group is bound to the scaffold by said 1 non- aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.
