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@ARTICLE{Amrhein:276862,
author = {J. A. Amrhein and G. Wang$^*$ and B.-T. Berger and L. M.
Berger and A. D. Kalampaliki and A. Krämer$^*$ and S.
Knapp$^*$ and T. Hanke},
title = {{D}esign and {S}ynthesis of {P}yrazole-{B}ased
{M}acrocyclic {K}inase {I}nhibitors {T}argeting {BMPR}2.},
journal = {ACS medicinal chemistry letters},
volume = {14},
number = {6},
issn = {1948-5875},
address = {Washington, DC},
publisher = {ACS},
reportid = {DKFZ-2023-01174},
pages = {833 - 840},
year = {2023},
abstract = {Bone morphogenetic protein (BMP) signaling is mediated by
transmembrane protein kinases that form heterotetramers
consisting of type-I and type-II receptors. Upon BMP
binding, the constitutively active type-II receptors
activate specific type-I receptors by transphosphorylation,
resulting in the phosphorylation of SMAD effector proteins.
Drug discovery in the receptor tyrosine kinase-like (TKL)
family has largely focused on type-I receptors, with few
inhibitors that have been published targeting type-II
receptors. BMPR2 is involved in several diseases, most
notably pulmonary arterial hypertension, but also
contributes to Alzheimer's disease and cancer. Here, we
report that macrocyclization of the promiscuous inhibitor 1,
based on a 3-amino-1H-pyrazole hinge binding moiety, led to
a selective and potent BMPR2 inhibitor 8a.},
subtyp = {Letter},
cin = {FM01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37312836},
pmc = {pmc:PMC10258821},
doi = {10.1021/acsmedchemlett.3c00127},
url = {https://inrepo02.dkfz.de/record/276862},
}