919347-65-2Relevant academic research and scientific papers
Discovery of an 8-methoxytetrahydroisoquinoline derivative as an orally active N-type calcium channel blocker for neuropathic pain without CYP inhibition liability
Ogiyama, Takashi,Yonezawa, Koichi,Inoue, Makoto,Katayama, Naoko,Watanabe, Toshihiro,Yoshimura, Seiji,Gotoh, Takayasu,Kiso, Tetsuo,Koakutsu, Akiko,Kakimoto, Shuichiro,Shishikura, Jun-Ichi
supporting information, p. 4638 - 4648 (2015/08/03)
In lead optimization efforts starting from the tetrahydroisoquinoline (S)-1, we identified 2-{[(2R)-2-hydroxypropyl]amino}-1-[(1S)-8-methoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone ((1S)-8t) as a novel orally active small-molecule N-type calcium channel blocker without CYP inhibition liability. CYP3A4 inhibition profile was improved by reducing the lipophilicity of compound (S)-1. Moreover, introduction of a methoxy group to the C-8 position of tetrahydroisoquinoline led to identification of (1S)-8t, which eliminated CYP2D6 inhibition liability. Oral administration of (1S)-8t exerted efficacy in a rat spinal nerve ligation (SNL) model of neuropathic pain with an ED50 value of 2.8 mg/kg.
Naphthamidine urokinase plasminogen activator inhibitors with improved pharmacokinetic properties
Bruncko, Milan,McClellan, William J.,Wendt, Michael D.,Sauer, Daryl R.,Geyer, Andrew,Dalton, Christopher R.,Kaminski, Michele A.,Weitzberg, Moshe,Gong, Jane,Dellaria, Joseph F.,Mantei, Robert,Zhao, Xumiao,Nienaber, Vicki L.,Stewart, Kent,Klinghofer, Vered,Bouska, Jennifer,Rockway, Todd W.,Giranda, Vincent L.
, p. 93 - 98 (2007/10/03)
A series of non-amide-linked 6-substituted-2-naphthamidine urokinase plasminogen activator (uPA) inhibitors are described. These compounds possess excellent binding activities and selectivities with significantly improved pharmacokinetic profiles versus p
