375856-23-8Relevant articles and documents
4-Aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase
Hanan, Emily J.,Baumgardner, Matt,Bryan, Marian C.,Chen, Yuan,Eigenbrot, Charles,Fan, Peter,Gu, Xiao-Hui,La, Hank,Malek, Shiva,Purkey, Hans E.,Schaefer, Gabriele,Schmidt, Stephen,Sideris, Steve,Yen, Ivana,Yu, Christine,Heffron, Timothy P.
supporting information, p. 534 - 539 (2016/01/09)
The treatment of epidermal growth factor receptor (EGFR)-driven non-small cell lung cancers with the T790M resistance mutation remains a significant unmet medical need. We report the identification of 4-aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of EGFR, with excellent activity against the T790M resistance double mutants and initial single activating mutants. Using an optimization strategy focused on structure-based design and improving PK properties through metabolite identification, we obtained advanced leads with high oral exposure.
Pyridine C-region analogs of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists
Ryu, Hyungchul,Seo, Sejin,Lee, Jee-Young,Ha, Tae-Hwan,Lee, Sunho,Jung, Aeran,Ann, Jihyae,Kim, Sung-Eun,Yoon, Suyoung,Hong, Mannkyu,Blumberg, Peter M.,Frank-Foltyn, Robert,Bahrenberg, Gregor,Schiene, Klaus,Stockhausen, Hannelore,Christoph, Thomas,Frormann, Sven,Lee, Jeewoo
, p. 101 - 108 (2015/03/05)
A series of pyridine derivatives in the C-region of N-((6-trifluoromethyl-pyridin-3-yl)methyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. The SAR analysis indicated that 6-difluorochloromethyl pyridine derivatives were the best surrogates of the C-region for previous leads. Among them, compound 31 showed excellent antagonism to capsaicin as well as to multiple hTRPV1 activators. It demonstrated stronganalgesic activity in the formalin test in mice with full efficacy and it blocked capsaicin-induced hypothermia in vivo.
