Preparation and optimization of pyrazolo[1,5- a ]pyrimidines as new potent PDE4 inhibitors

Water molecules at protein–drug interfaces: computational prediction and analysis methods

“…16 (16) SuperStar 47,48 Scatter plots of water positions around functional groups from the IsoStar knowledge base are mapped onto a structure.…”

“…1). 14 Further examples include small molecules that target TYK2 and JAK3 kinases, 15 PDE4 inhibitors 16 and Adenosine A2A inhibitors. 17 A notable example currently in clinical trials is the molecule GLP1690, developed by Galapagos, which is a first-inclass molecule for idiopathic pulmonary fibrosis, where the effect of the nitrile group is thought to be governed by water displacement.…”

Advances in the Development of Phosphodiesterase-4 Inhibitors

“…94 Modification of the pyrazolopyridine scaffold led to preparation of compound 41 (IC 50 = 26 nM, Figure 16). 95 Molecular docking of compound 41 to the crystal structure of PDE4B showed that interactions of the amide, 3-methoxyaryl, and sulfone groups with PDE4B completely coincide with those of compound 28 (PDB code 3GWT, Figure 14). A nitrogen in the heterocyclic ring and the amide form hydrogen bonds with Gln443 through a water molecule, in addition to a hydrogen bond between the amide of 39 and Asn395.…”

Synthesis and Nematocidal Activity of N‐Substituted 3‐Methyl‐1H‐pyrazole‐4‐carboxamide Derivatives Against Meloidogyne incognita

“…Some pyrazole compounds have been developed as commercial drugs and pesticides, such as tebufenpyral, fipronil, fenpyroximate, tolfenpyrad, and chlorantraniliprole. In addition, carboxamide is a key substructure in many compounds, which displayed various biological activities, such as antifungal, herbicidal, insecticidal , antiproliferative , PDE4 inhibitors, and anti‐hepatitis C virus . Many carboxamide fungicides had been developed by BASF, Bayer, Syngenta, Monsanto, Sumitomo Chemical, and so on.…”