87166-49-2Relevant academic research and scientific papers
Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
Bollenbach, Maud,Lugnier, Claire,Kremer, Mélanie,Salvat, Eric,Megat, Salim,Bihel, Frédéric,Bourguignon, Jean-Jacques,Barrot, Michel,Schmitt, Martine
, p. 269 - 290 (2019/06/05)
Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50 = 3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole)were evaluated in comparison to MY 5445 (4b)in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment.
Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells
Medda, Federico,Sells, Earlphia,Chang, Hui-Hua,Dietrich, Justin,Chappeta, Shashi,Smith, Breland,Gokhale, Vijay,Meuillet, Emmanuelle J.,Hulme, Christopher
, p. 528 - 531 (2013/02/25)
This Letter reports the synthesis and biological evaluation of a collection of aminophthalazines as a novel class of compounds capable of reducing production of PGE2 in HCA-7 human adenocarcinoma cells. A total of 28 analogs were synthesized, a
Arylphthalazines: Identification of a new phthalazine chemotype as inhibitors of VEGFR kinase
Piatnitski, Evgueni L.,Duncton, Matthew A. J.,Kiselyov, Alexander S.,Katoch-Rouse, Reeti,Sherman, Dan,Milligan, Daniel L.,Balagtas, Chris,Wong, Wai C.,Kawakami, Joel,Doody, Jacqueline F.
, p. 4696 - 4698 (2007/10/03)
A novel class of 4-arylamino-phthalazin-1-yl-benzamides is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display potent VEGFR-2 inhibitory activity with an IC50 as low as 0.078 μM in an H
