2 research outputs found
Piperazine-Based CCR5 Antagonists as HIV-1 Inhibitors. II. Discovery of 1-[(2,4-Dimethyl-3-pyridinyl)carbonyl]-4- methyl-4-[3( S
Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5‑Chloro‑<i>N</i>2‑(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)‑<i>N</i>4‑(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials
The synthesis, preclinical profile,
and in vivo efficacy in rat xenograft models of the novel and selective
anaplastic lymphoma kinase inhibitor <b>15b</b> (LDK378) are
described. In this initial report, preliminary structure–activity
relationships (SARs) are described as well as the rational design
strategy employed to overcome the development deficiencies of the
first generation ALK inhibitor <b>4</b> (TAE684). Compound <b>15b</b> is currently in phase 1 and phase 2 clinical trials with
substantial antitumor activity being observed in ALK-positive cancer
patients