Tag: M.W=200-250

Czako, Barbara published the artcileDiscovery of 6-[(3S,4S)-4-Amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methyl-3,4-dihydropyrimidin-4-one (IACS-15414), a Potent and Orally Bioavailable SHP2 Inhibitor, Application In Synthesis of 2055761-19-6, the publication is Journal of Medicinal Chemistry (2021), 64(20), 15141-15169, database is CAplus and MEDLINE.

Src homol. 2 (SH2) domain-containing phosphatase 2 (SHP2) plays a role in receptor tyrosine kinase (RTK), neurofibromin-1 (NF-1), and Kirsten rat sarcoma virus (KRAS) mutant-driven cancers, as well as in RTK-mediated resistance, making the identification of small-mol. therapeutics that interfere with its function of high interest. Our quest to identify potent, orally bioavailable, and safe SHP2 inhibitors led to the discovery of a promising series of pyrazolopyrimidinones that displayed excellent potency but had a suboptimal in vivo pharmacokinetic (PK) profile. Hypothesis-driven scaffold optimization led us to a series of pyrazolopyrazines with excellent PK properties across species but a narrow human Ether-á-go-go-Related Gene (hERG) window. Subsequent optimization of properties led to the discovery of the pyrimidinone series, in which multiple members possessed excellent potency, optimal in vivo PK across species, and no off-target activities including no hERG liability up to 100μM. Importantly, compound 30 (IACS-15414) potently suppressed the mitogen-activated protein kinase (MAPK) pathway signaling and tumor growth in RTK-activated and KRAS^mut xenograft models in vivo.

Journal of Medicinal Chemistry published new progress about 2055761-19-6. 2055761-19-6 belongs to chiral-phosphine-ligands, auxiliary class Spiro[4.5], name is (3S,4S)-3-Methyl-2-oxa-8-azaspiro[4.5]decan-4-amine dihydrochloride, and the molecular formula is C9H20Cl2N2O, Application In Synthesis of 2055761-19-6.

Referemce:
https://en.wikipedia.org/wiki/Phosphine_ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate

Yang, Xiangbo published the artcileDiscovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders, Product Details of C9H20Cl2N2O, the publication is European Journal of Medicinal Chemistry (2021), 113341, database is CAplus and MEDLINE.

Design, synthesis and evaluation of a series of thalidomide-based heterobifunctional mols. and identified compound I as highly efficient SHP2 degrader with a DC₅₀ of 6.02 nM was described. Further mechanism investigation illustrated that compound I came into function through targeted SHP2 protein degradation

European Journal of Medicinal Chemistry published new progress about 2055761-19-6. 2055761-19-6 belongs to chiral-phosphine-ligands, auxiliary class Spiro[4.5], name is (3S,4S)-3-Methyl-2-oxa-8-azaspiro[4.5]decan-4-amine dihydrochloride, and the molecular formula is C16H24BF4Ir, Product Details of C9H20Cl2N2O.

Referemce:
https://en.wikipedia.org/wiki/Phosphine_ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate