156939-62-7Relevant articles and documents
Protection of ψ(CH2NH) peptide bond with 2,4-dimethoxybenzyl group in solid-phase peptide synthesis
Sasaki, Yusuke,Abe, Junko
, p. 13 - 17 (1997)
The reductive alkylation of a resin-bound amine by the Boc-amino aldehyde/NaBH3CN method is accompanied with undesirable double alkylation at Xaaψ(CH2NH)Gly sequences. To prevent the double alkylation, the utility of the 2,4-dimethox
Multivalent drug design. Synthesis and in vitro analysis of an array of vancomycin dimers
Griffin, John H.,Linsell, Martin S.,Nodwell, Matthew B.,Chen, QiQi,Pace, John L.,Quast, Kelly L.,Krause, Kevin M.,Farrington, Lesley,Wu, Terry X.,Higgins, Deborah L.,Jenkins, Thomas E.,Christensen, Burton G.,Judice, J. Kevin
, p. 6517 - 6531 (2003)
The design, synthesis, and in vitro microbiological analysis of an array of forty covalently linked vancomycin dimers are reported. This work was undertaken to systematically probe the impact of linkage orientation and linker length on biological activity
Synthesis of triamino acid building blocks with different lipophilicities
Maity, Jyotirmoy,Honcharenko, Dmytro,Str?mberg, Roger
, (2015)
To obtain different amino acids with varying lipophilicity and that can carry up to three positive charges we have developed a number of new triamino acid building blocks. One set of building blocks was achieved by aminoethyl extension, via reductive amination, of the side chain of ortnithine, diaminopropanoic and diaminobutanoic acid. A second set of triamino acids with the aminoethyl extension having hydrocarbon side chains was synthesized from diaminobutanoic acid. The aldehydes needed for the extension by reductive amination were synthesized from the corresponding Fmoc-L-2-amino fatty acids in two steps. Reductive amination of these compounds with Boc-L-Dab-OH gave the C4-C8 alkyl-branched triamino acids. All triamino acids were subsequently Boc-protected at the formed secondary amine to make the monomers appropriate for the N-terminus position when performing Fmoc-based solid-phase peptide synthesis.
A Fmoc-based submonomeric strategy for the solid phase synthesis of optically pure chiral PNAs
Tedeschi, Tullia,Sforza, Stefano,Maffei, Francesca,Corradini, Roberto,Marchelli, Rosangela
, p. 4958 - 4961 (2008)
A new submonomeric approach for the Fmoc solid phase synthesis of chiral PNAs is reported here. The design and synthesis of a new d-lysine-based Fmoc submonomer obtained by replacing the nucleobase residue with an Alloc group, compatible with Fmoc chemistry, is described starting from d-lysine and Fmoc-aminoacetaldehyde. The desired submonomer was obtained in high yield with no racemization. The conditions for synthesizing a chiral PNA dimer on solid support by a submonomeric approach have been optimized, allowing to obtain the desired PNA with a very high optical purity.
Solid-phase synthesis of PhTX-3.2.4 and PhTX-2.3.3 derivatives
J?nsson, Daniel
, p. 4793 - 4796 (2002)
A new solid-phase method for the synthesis of derivatives of the philanthotoxins is described. Diamines are attached as carbamates to hydroxymethyl polystyrene resin. Selective mono-alkylations by acid-labile, substituted benzhydryl chlorides, followed by reductive alkylations with Fmoc-protected amino aldehydes are employed to assemble the polyamine backbone. Different acid-stability of the benzhydrylic protective groups allows the selective removal from secondary amines for subsequent branching.
[1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-5-AMINES
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Page/Page column 241, (2021/02/19)
The present invention covers [1,2,4]triazolo[1,5-c]quinazolin-5-amine compounds of general formula (I) in which R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients.
Development and preclinical evaluation of new inhaled lipoglycopeptides for the treatment of persistent pulmonary methicillin-resistant staphylococcus aureus infections
Plaunt, Adam J.,Rose, Sasha J.,Kang, Jeong Yeon,Chen, Kuan-Ju,LaSala, Daniel,Heckler, Ryan P.,Dorfman, Arielle,Smith, Barrett T.,Chun, Donald,Viramontes, Veronica,Macaluso, Antonio,Li, Zhili,Zhou, Yuchen,Mark, Lilly,Basso, Jessica,Leifer, Franziska G.,Corboz, Michel R.,Chapman, Richard W.,Cipolla, David,Perkins, Walter R.,Malinin, Vladimir S.,Konicek, Donna M.
supporting information, (2021/06/22)
Chronic pulmonary methicillin-resistant Staphylococcus aureus (MRSA) disease in cystic fibrosis (CF) has a high probability of recurrence following treatment with standard-of-care antibiotics and represents an area of unmet need associated with reduced life expectancy. We developed a lipoglycopeptide therapy customized for pulmonary delivery that not only demonstrates potent activity against planktonic MRSA, but also against protected colonies of MRSA in biofilms and within cells, the latter of which have been linked to clinical antibiotic failure. A library of next-generation potent lipoglycopeptides was synthesized with an emphasis on attaining superior pharmacokinetics (PK) and pharmacodynamics to similar compounds of their class. Our strategy focused on hydrophobic modification of vancomycin, where ester and amide functionality were included with carbonyl configuration and alkyl length as key variables. Candidates representative of each carbonyl attachment chemistry demonstrated potent activity in vitro, with several compounds being 30 to 60 times more potent than vancomycin. Selected compounds were advanced into in vivo nose-only inhalation PK evaluations in rats, where RV94, a potent lipoglycopeptide that utilizes an inverted amide linker to attach a 10-carbon chain to vancomycin, demonstrated the most favorable lung residence time after inhalation. Further in vitro evaluation of RV94 showed superior activity to vancomycin against an expanded panel of Gram-positive organisms, cellular accumulation and efficacy against intracellular MRSA, and MRSA biofilm killing. Moreover, in vivo efficacy of inhaled nebulized RV94 in a 48 h acute model of pulmonary MRSA (USA300) infection in neutropenic rats demonstrated statistically significant antibacterial activity that was superior to inhaled vancomycin.
PEPTIDE NUCLEIC ACID (PNA) MONOMERS WITH AN ORTHOGONALLY PROTECTED ESTER MOIETY
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, (2018/10/19)
This application pertains to orthogonally protected esters of peptide nucleic acid (PNA) monomers, which ester groups can be removed under conditions that permit typical backbone and side chain acid- and base-labile protecting groups to remain substantially intact thereby permitting the high yield of PNA monomer carboxylic acids that are suitable for use in PNA oligomer synthesis. Exemplary ester groups include, but are not limited to, 2,2,2-trichloroethyl (TCE), 2,2,2-tribromoethyl (TBE), 2-bromoethyl (2-BE) and 2-iodoethyl groups (2-IE). This invention also pertains to novel methods for the synthesis of Backbone Ester compounds and related Backbone Ester Acid Salts.
MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
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Paragraph 001283; 001284, (2018/09/12)
Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
Inverse γ-Turn-Inspired Peptide: Synthesis and Analysis of Segetalin A Indole Hemiaminal
Lamping, Matthias,Enck, Sebastian,Geyer, Armin
, p. 7443 - 7448 (2016/01/26)
Substitution of a peptide bond for an imine transforms the irreversible macrocyclization of peptides into a reversible process. The inherent cyclization tendency of a linear peptide is then analyzable through the equilibrium between the aldehyde and the imine by virtue of the higher reactivity of the corresponding linear peptide aldehyde. The tryptophan side chain of segetalin A aldehyde forms a 12-membered cyclic indole hemiaminal instead of the 18-membered macrocyclic imine expected. Herein, we analyzed this uncommon hemiaminal that shows that the biosynthesis of cyclic peptides is not necessarily based on linear precursor peptides with a high inherent macrolactamization tendency. By substituting a peptide bond for an imine, the cyclization tendency of a linear peptide can be analyzed through equilibration of the aldehyde and imine forms. The tryptophan side chain of segetalin A aldehyde forms a 12-membered cyclic indole hemiaminal instead of the expected 18-membered macrocyclic imine. Herein, we analyze this uncommon hemiaminal.
