16078-71-0Relevant articles and documents
Design, synthesis and anti-P. falciparum activity of pyrazolopyridine–sulfonamide derivatives
Silva, Thais B.,Bernardino, Alice M.R.,Ferreira, Maria de Lourdes G.,Rogerio, Kamilla R.,Carvalho, Leonardo J.M.,Boechat, Nubia,Pinheiro, Luiz C.S.
, p. 4492 - 4498 (2016)
Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50values ranging from 3.46 to 9.30 μM. The most active derivatives with substituent R2= Cl or CH3at the benzenesulfonamide moiety exhibited the lowest IC50. Compounds with an R1= CO2Et substituent at the 5-position of the 1H-pyrazolo[3,4-b]pyridine ring presented lower activity than those with a CN substituent. The 1H-pyrazolo[3,4-b]pyridine system appears to be promising for further studies as an antimalarial for overcoming the burden of resistance in P. falciparum.
COMPOUNDS HAVING PDE9A INHIBITORY ACTIVITY, AND PHARMACEUTICAL USES THEREOF
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Paragraph 0220-0221, (2021/10/15)
The present invention provides a compound having a specific chemical structure and having PDE9A inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention provides a composition containing the compound or a pharmaceutically acceptable salt thereof. The present invention provides a pharmaceutical use, for treating or preventing PDE9A-related diseases, of the compound according to the present invention, a salt thereof, and a composition containing the compound or salt. The present invention also provides a method for treating or preventing PDE9A-related diseases, the method comprising administering an effective amount of the compound according to the present invention, a salt thereof, or a composition containing the compound or salt to a subject in need of treatment.
Novel Pyrazolo[3,4- d]pyrimidin-4-one Derivatives as Potential Antifungal Agents: Design, Synthesis, and Biological Evaluation
Cheng, Xiang,Wang, Wei,Wang, Yunxiao,Xia, Dongguo,Yin, Fang,Liu, Qiaoyun,Luo, Huisheng,Li, Meng,Zhang, Chengqi,Cao, Haiqun,Lv, Xianhai
, p. 11395 - 11405 (2021/10/01)
Plant pathogenic fungi seriously threaten agricultural production. There is an urgent need to develop novel fungicides with low toxicity and high efficiency. In this study, we designed and synthesized 44 pyrazolo[3,4-d]pyrimidin-4-one derivatives and evaluated them for their fungicidal activities. The bioassay data revealed that most of the target compounds possessed moderate to high in vitro antifungal activities. Especially compound g22 exhibited remarkable antifungal activity against Sclerotinia sclerotiorum with an EC50 value of 1.25 mg/L, close to that of commercial fungicide boscalid (EC50 = 0.96 mg/L) and fluopyram (EC50 = 1.91 mg/L). Moreover, compound g22 possessed prominent protective activity against S. sclerotiorum in vivo for 24 h (95.23%) and 48 h (93.78%), comparable to positive control boscalid (24 h (96.63%); 48 h (93.23%)). Subsequent studies indicated that compound g22 may impede the growth and reproduction of S. sclerotiorum by affecting the morphology of mycelium, destroying cell membrane integrity, and increasing cell membrane permeability. In addition, the application of compound g22 did not injure the growth or reproduction of Italian bees. This study revealed that compound g22 is expected to be developed for efficient and safe agricultural fungicides.
Selective targeting of the αC and DFG-out pocket in p38 MAPK
R?hm, Sandra,Schr?der, Martin,Dwyer, Jessica E.,Widdowson, Caroline S.,Chaikuad, Apirat,Berger, Benedict-Tilman,Joerger, Andreas C.,Kr?mer, Andreas,Harbig, Jule,Dauch, Daniel,Kudolo, Mark,Laufer, Stefan,Bagley, Mark C.,Knapp, Stefan
, (2020/10/09)
The p38 MAPK cascade is a key signaling pathway linked to a multitude of physiological functions and of central importance in inflammatory and autoimmune diseases. Although studied extensively, little is known about how conformation-specific inhibitors alter signaling outcomes. Here, we have explored the highly dynamic back pocket of p38 MAPK with allosteric urea fragments. However, screening against known off-targets showed that these fragments maintained the selectivity issues of their parent compound BIRB-796, while combination with the hinge-binding motif of VPC-00628 greatly enhanced inhibitor selectivity. Further efforts focused therefore on the exploration of the αC-out pocket of p38 MAPK, yielding compound 137 as a highly selective type-II inhibitor. Even though 137 is structurally related to a recent p38 type-II chemical probe, SR-318, the data presented here provide valuable insights into back-pocket interactions that are not addressed in SR-318 and it provides an alternative chemical tool with good cellular activity targeting also the p38 back pocket.