3PTG

Design and Synthesis of a Novel, Orally Efficacious Tri-substituted Thiophene Based JNK Inhibitor

Summary for 3PTG

• Entry DOI: 10.2210/pdb3ptg/pdb
• Descriptor: Mitogen-activated protein kinase 10, C-Jun-amino-terminal kinase-interacting protein 1, N-[4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide, ... (4 entities in total)
• Functional Keywords: jnk inhibitor, thiophene, neurodegeneration, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P53779; Cytoplasm (By similarity): Q9UQF2
• Total number of polymer chains: 2
• Total formula weight: 43583.48

Authors

Bowers, S.,Truong, A.P.,Neitz, J.,Neitzel, M.,Probst, G.D.,Hom, R.K.,Konradi, A.W.,Sham, H.L.,Toth, G.,Pan, H.,Yao, N.,Artis, D.R.,Brigham, E.F.,Quinn, K.P.,Sauer, J.,Powell, K.,Ruslim, L.,Bard, F.,Yednock, T.A.,Griswold-Prenner, I. (deposition date: 2010-12-02, release date: 2011-03-02, Last modification date: 2024-02-21)

Primary citation

Bowers, S.,Truong, A.P.,Neitz, R.J.,Neitzel, M.,Probst, G.D.,Hom, R.K.,Peterson, B.,Galemmo, R.A.,Konradi, A.W.,Sham, H.L.,Toth, G.,Pan, H.,Yao, N.,Artis, D.R.,Brigham, E.F.,Quinn, K.P.,Sauer, J.M.,Powell, K.,Ruslim, L.,Ren, Z.,Bard, F.,Yednock, T.A.,Griswold-Prenner, I.
Design and synthesis of a novel, orally active, brain penetrant, tri-substituted thiophene based JNK inhibitor.
Bioorg.Med.Chem.Lett., 21:1838-1843, 2011

PubMed Abstract: The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction.

PubMed: 21316234
DOI: 10.1016/j.bmcl.2011.01.046

Experimental method

X-RAY DIFFRACTION (2.43 Å)