117751-86-7Relevant articles and documents
RIP1K INHIBITORS
-
Page/Page column 61; 62, (2021/10/11)
Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceut
Prodrug forms of N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-γ- [ψP(O)(OH)]-glutarate, a potent inhibitor of folylpoly-γ-glutamate synthetase: Synthesis and hydrolytic stability
Feng, Yan,Coward, James K.
, p. 770 - 788 (2007/10/03)
Ester prodrugs of the phosphinate pseudopeptide N-[(4-deoxy-4-amino-10- methyl)pteroyl]glutamate-γ-[ψP-(O)(OH)]-glutarate (1a) were synthesized. H-phosphinic acids derived from N-Cbz vinyl glycine esters were converted to the desired pseudopeptides by Michael addition to α-methyleneglutarate esters. Pivaloyloxymethyl (POM) ester moieties were incorporated in both the N-terminal and C-terminal fragments prior to formation of either C-P bond, N-Alkylation of the corresponding amides derived from N-(N-methyl)aminobenzoic acid with 2,4-diamino-6-(bromomethyl)pteridine gave the target compounds. POM esters of methotrexate and the corresponding γ-glutamyl conjugate were also synthesized using the same strategy. All prodrugs were evaluated in Chinese hamster ovary cells. Although the pseudopeptide prodrugs were ineffective, prodrugs of methotrexate and the corresponding γ-glutamyl conjugate were equipotent with the parent compounds. Stability of the prodrugs was investigated in both phosphate buffer and cell line medium to provide a rationale for the observed biological data.
Palladium(O) catalysed and copper(I) promoted reactions of the secondary zinc reagent derived from L-threonine
Wilson, Ian,Jackson, Richard F.W.
, p. 2845 - 2850 (2007/10/03)
The preparation of C-3 epimeric secondary zinc reagents from diastereoisomeric iodide using DMF as solvent was discussed and analyzed by NMR methods. Palladium catalysed cross couplings and copper promoted allylations produced protected β-methyl substituted amino acids. It was concluded that the threonine derived zinc reagents were of limited values, but further optimization of copper-promoted reactions make this approach to synthesis of β-methyl substituted α-amino acids more useful.