Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization.
Based on an (aminoaryl)benzothiazole quinazoline hit structure for kinase inhibition, a systematic optimization program resulted in a lead structure allowing for inhibitory activities in cellular phosphorylation assays in the low nanomolar range.
Tasler
Stefan
S
4SC AG, Am Klopferspitz 19a, 82152 Planegg-Martinsried, Germany.
Müller
Oliver
O
Wieber
Tanja
T
Herz
Thomas
T
Pegoraro
Stefano
S
Saeb
Wael
W
Lang
Martin
M
Krauss
Rolf
R
Totzke
Frank
F
Zirrgiebel
Ute
U
Ehlert
Jan E
JE
Kubbutat
Michael H G
MH
Schächtele
Christoph
C
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D064127:Aurora Kinases; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D066246:ErbB Receptors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C005465:benzothiazole