51517-01-2Relevant 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.
NOVEL INHIBITORS OF PROTEIN KINASES
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Paragraph 0093; 0135; 0137, (2017/09/08)
Protein kinases are regulators of cellular signaling and their functional dysregulation is common in carcinogenesis and many other disease states or disorders. The present invention relates to novel chemical entities that have biological activity to modulate mammalian protein kinase enzymes. In particular, compounds of the invention display potent inhibition of breast tumor related kinase (BRK).
Aminotetrahydropyran derivative used as dipeptidyl peptidase-IV inhibitor
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Paragraph 0171; 0172, (2016/10/09)
The invention provides an aminotetrahydropyran derivative as shown in the general formula (I), pharmaceutically acceptable salt, hydrate, solvate and stereisomer of the derivative, a preparation method thereof, and a pharmaceutical composition containing the compound. The compound can inhibit activity of dipeptidyl peptidase IV (DPP-IV) and can be used in treating diseases related to dipeptidyl peptidase IV.