4025-71-2Relevant articles and documents
From off-to on-target: New BRAF-inhibitor-template-derived compounds selectively targeting mitogen activated protein kinase kinase 4 (MKK4)
Kl?vekorn, Philip,Pfaffenrot, Bent,Juchum, Michael,Selig, Roland,Albrecht, Wolfgang,Zender, Lars,Laufer, Stefan A.
supporting information, (2020/11/20)
The mitogen-activated protein kinase (MAP) kinase 4 (MKK4) was found to be a major regulator of liver regeneration and could be a valuable drug target addressing liver related diseases by restoring its intrinsic regenerative capacity. We report on the synthesis and optimization of novel MKK4 inhibitors following a target-hopping strategy from the FDA-approved BRAFV600E inhibitor PLX4032 (8). Applying an iterative multi-parameter optimization process we carved out essential structural features yielding in compounds with a low nanomolar affinity for MKK4 and excellent selectivity profiles against the main off-targets MKK7 and JNK1, which, upon relevant inhibition, would totally abrogate the pro-regenerative effect of MKK4 inhibition, as well as against the off-targets MAP4K5, ZAK and BRAF with selectivity factors ranging from 40 to 430 for our best-balanced compounds 70 and 73.
Searching for novel N1-substituted benzimidazol-2-ones as non-nucleoside HIV-1 RT inhibitors
Ferro, Stefania,Buemi, Maria Rosa,De Luca, Laura,Agharbaoui, Fatima E.,Pannecouque, Christophe,Monforte, Anna-Maria
, p. 3861 - 3870 (2017/06/13)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an integral part of the currently available combination antiretroviral therapy (cART) contributing to reduce the AIDS-mortality and turned the disease from lethal to chronic. In this conte
Remote meta C-H bond functionalization of 2-phenethylsulphonic acid and 3-phenylpropanoic acid derivatives
Modak, Atanu,Mondal, Anirban,Watile, Rahul,Mukherjee, Semanti,Maiti, Debabrata
supporting information, p. 13916 - 13919 (2016/12/06)
This discovery illustrates selective meta C-H bond activation from multiple non-equivalent C-H bonds present in medicinally relevant arylethanesulfonic acid and the 2-arylpropanoic acid moiety using weakly coordinating nitrile as a directing group. Transformation of the meta olefinated compounds to important organic molecules has been demonstrated. Efforts were made to obtain mechanistic detail of the meta C-H bond functionalization reaction.