78553-60-3Relevant academic research and scientific papers
NOVEL HISTONE METHYLTRANSFERASE INHIBITORS
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, (2021/04/01)
The present invention relates to novel compounds of formula (I) as defined herein. The compounds are inhibitors of histone methyltransferases of the seven-beta-strand family, in particular of KMT9.
Synthesis of Two Epimers of Pseudopaline
Arnoux, Pascal,Cavelier, Florine,Cullia, Gregorio,Fanelli, Roberto,Voulhoux, Romé
, (2020/07/06)
Opines are a known group of compounds characterized by an elevated polarity. Recently, two new members of this class, staphylopine and pseudopaline, have been identified in Staphylococcus aureus and Pseudomonas aeruginosa, respectively. These molecules are metal chelators that contribute to the growth of bacteria in particularly metal-poor environment. Different evidences suggest that these molecules might have an important role in the development of pulmonary infections in humans. Considering the impact of P. aeruginosa infections in cystic fibrosis patients (prevalence up to 70 percent), pseudopaline has risen interest as potential source of new therapeutic intervention. We present herein a straightforward synthetic approach for the synthesis of the two epimers of pseudopaline. Starting from a chiral building block, we attribute the absolute configuration to the two obtained diasteroisomers.
Development of rationally designed DNA N6 adenine methyltransferase inhibitors
Hobley, Gerard,McKelvie, Jennifer C.,Harmer, Jenny E.,Howe, Jason,Oyston, Petra C.F.,Roach, Peter L.
, p. 3079 - 3082 (2012/06/17)
A series of bisubstrate inhibitors for DNA N6 adenine methyltransferase (Dam) have been synthesized by linking an amine analogue of S-adenosylmethionine to an aryl moiety designed to probe the binding pocket of the DNA adenine base. An initial structure-activity relationship study has identified substituents that increase inhibitor potency to the ～10 μM range and improve selectivity against the human cytosine methyltransferase Dnmt1.
Synthesis of a trisubstituted 1,4-diazepin-3-one-based dipeptidomimetic as a novel molecular scaffold
Weitz, Iris S.,Pellegrini, Maria,Mierke, Dale F.,Chorev, Michael
, p. 2527 - 2534 (2007/10/03)
We describe two routes for the synthesis of a trisubstituted 1,2,5-hexahydro-3-oxo-1H-1,4-diazepine ring (DAP), a novel, conformationally constrained, seven-membered dipeptidomimetic ring system. The linear precursor for the model DAPs, targeted for conformational analysis studies, was obtained by reductive alkylation of tert-butyl alaninate or phenylalaninate by N-Boc-α-amino-γ-oxo-N,N-dimethylbutyramide. Acetylation of the newly formed secondary amine followed by acidolytic deprotection of the amino and carboxyl terminal protecting groups and subsequent diphenylphosphorazidate-mediated ring formation yielded the blocked model DAPs. The synthesis of the DAP synthon started with 1-tert-butyl hydrogen N-(benzyloxycarbonyl)aspartate. The aldehyde obtained from the β-carboxyl was used to reductively alkylate benzyl phenylalaninate, generating a secondary amine. Hydrogenolytic deprotection of the end-groups yielded the linear precursor which was cyclized via lactam formation mediated by 1-hydroxy-7-azabenzotriazolyl-N,N,N',N'-tetramethyluronium hexafluorophosphate. This route yielded the reversibly protected hexahydro-1H-3-oxo-2(S)-benzyl-5(S)-(tert-butyloxycarbonyl)-1,4-diazep ine. This synthon unit can be subsequently elaborated by substituting the functional groups (secondary amine and carboxyl). Therefore, the DAPs may serve as novel molecular scaffolds to reproduce a biologically relevant topology or as a dipeptido-conformation-mimetic that can be incorporated into bioactive peptides. In addition, these synthetic routes will allow the introduction of different chiralities at positions 2 and 5 as well as the diversification of the side chains at position 2. Furthermore, the synthetic routes described here can be easily modified to obtain larger ring systems with variable degrees of conformational flexibility.
Synthesis of Optically Active 2-(tert-Butyloxycarbonylamino)-4-dialkoxyphosphorylbutanoate Protected Isosteres of O-Phosphonoserine for Peptide Synthesis
Valerio, R. M.,Alewood, P. F.,Johns, R. B.
, p. 786 - 789 (2007/10/02)
The preparation of (S)-2-(tert-butoxycarbonylamino)-4-dialkoxyphosphorylbutanoate from (S)-aspartic acid is described.
SYNTHESIS OF NICOTIANAMINE AND A RELATED COMPOUND, DERIVATIVES OF AZETIDINE-2-CARBOXYLIC ACID
Fushiya, Shinji,Nakatsuyama, Shuichi,Sato, Yoshikazu,Nozoe, Shigeo
, p. 819 - 822 (2007/10/02)
The synthesis of nicotianamine (1) and a related compound (2) - amino acid derivatives having the azetidine ring - was achieved by reductive coupling of L-aspartic-β-semialdehyde derivatives with L-azetidine-2-carboxylic acid methyl ester.
