3RTP

Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration

Summary for 3RTP

• Entry DOI: 10.2210/pdb3rtp/pdb
• Descriptor: Mitogen-activated protein kinase 10, N-[4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide (3 entities in total)
• Functional Keywords: jnk inhibitors, pharmacokinetic properties, neurodegeneration, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P53779
• Total number of polymer chains: 1
• Total formula weight: 42248.85

Authors

Bowers, S.,Truong, A.P.,Neitz, R.J.,Hom, R.K.,Sealy, J.M.,Probst, G.D.,Quincy, Q.,Peterson, B.,Chan, W.,Galemmo Jr., R.A.,Konradi, A.W.,Sham, H.L.,Pan, H.,Lin, M.,Yao, N.,Artis, D.R.,Zhang, H.,Chen, L.,Dryer, M.,Samant, B.,Zmolek, W.,Wong, K.,Lorentzen, C.,Goldbach, E.,Tonn, G.,Quinn, K.P.,Sauer, J.,Wright, S.,Powell, K.,Ruslim, L.,Ren, Z.,Bard, F.,Yednock, T.A.,Griswold-Prenne, I. (deposition date: 2011-05-03, release date: 2013-05-08, Last modification date: 2024-02-28)

Primary citation

Bowers, S.,Truong, A.P.,Jeffrey Neitz, R.,Hom, R.K.,Sealy, J.M.,Probst, G.D.,Quincy, D.,Peterson, B.,Chan, W.,Galemmo, R.A.,Konradi, A.W.,Sham, H.L.,Toth, G.,Pan, H.,Lin, M.,Yao, N.,Artis, D.R.,Zhang, H.,Chen, L.,Dryer, M.,Samant, B.,Zmolek, W.,Wong, K.,Lorentzen, C.,Goldbach, E.,Tonn, G.,Quinn, K.P.,Sauer, J.M.,Wright, S.,Powell, K.,Ruslim, L.,Ren, Z.,Bard, F.,Yednock, T.A.,Griswold-Prenner, I.
Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration.
Bioorg.Med.Chem.Lett., 21:5521-5527, 2011

PubMed Abstract: The SAR of a series of brain penetrant, trisubstituted thiophene based JNK inhibitors with improved pharmacokinetic properties is described. These compounds were designed based on information derived from metabolite identification studies which led to compounds such as 42 with lower clearance, greater brain exposure and longer half life compared to earlier analogs.

PubMed: 21813278
DOI: 10.1016/j.bmcl.2011.06.100

Experimental method

X-RAY DIFFRACTION (2.4 Å)