96319-38-9Relevant academic research and scientific papers
IRAK DEGRADERS AND USES THEREOF
-
Paragraph 00651; 00653-00654, (2021/08/13)
The present invention provides compounds, compositions thereof, and methods of using the same.
Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders
Mikami, Satoshi,Sasaki, Shigekazu,Asano, Yasutomi,Ujikawa, Osamu,Fukumoto, Shoji,Nakashima, Kosuke,Oki, Hideyuki,Kamiguchi, Naomi,Imada, Haruka,Iwashita, Hiroki,Taniguchi, Takahiko
, p. 7658 - 7676 (2017/10/06)
Herein, we describe the discovery of a potent, selective, brain-penetrating, in vivo active phosphodiesterase (PDE) 2A inhibitor lead series. To identify high-quality leads suitable for optimization and enable validation of the physiological function of PDE2A in vivo, structural modifications of the high-throughput screening hit 18 were performed. Our lead generation efforts revealed three key potency-enhancing functionalities with minimal increases in molecular weight (MW) and no change in topological polar surface area (TPSA). Combining these structural elements led to the identification of 6-methyl-N-((1R)-1-(4-(trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (38a), a molecule with the desired balance of preclinical properties. Further characterization by cocrystal structure analysis of 38a bound to PDE2A uncovered a unique binding mode and provided insights into its observed potency and PDE selectivity. Compound 38a significantly elevated 3′,5′-cyclic guanosine monophosphate (cGMP) levels in mouse brain following oral administration, thus validating this compound as a useful pharmacological tool and an attractive lead for future optimization.
Systemic Fungicides. The Synthesis of Pyrazolopyrimidine Analogues of Carboxin
Huppatz, John L.
, p. 221 - 230 (2007/10/02)
The synthesis of a series of pyrazolopyrimidine derivatives, structural analogues of the systemic fungicide carboxin, is described.A common intermediate incorporating structural features desirable for fungicidal activity, N-phenyl-3(5)-amino-5(3)-m
