223678-66-8Relevant articles and documents
Omegatides: Constrained analogs of peptide primary sequence
Fedoseyenko, Dmytro,Raghuraman, Arjun,Ko, Eunhwa,Burgess, Kevin
, p. 921 - 924 (2012)
A study was conducted to demonstrate a design for contiguous constrained amino acid surrogates, called omegatides, that had side chains to reflect the primary sequence di- and tri-peptides. A solution phase strategy for the preparation of omegatides was developed, which started with 5-substituted 2,4-pyrrolidinediones (tetramic acids) A that were prepared from amino acids on multigram scales via a one-pot procedure without chromatography. Procedures were developed to add an amino acid to analogous compounds and to reduce the resulting vinylogous ureas. Two methods were used to assess the conformational biases and constraints on these systems. The first was quenched molecular dynamics (QMD) to probe thermodynamic accessibility of conformational states. The molecule was energy minimized and subjected to a molecular dynamics run at high temperature for a short time in this technique and conformational states were recorded every 1 ps and minimized via molecular mechanics.
TYK2 INHIBITORS AND USES THEREOF
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Paragraph 00707-00708, (2017/03/21)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
Expanding the scope of oligo-pyrrolinone-pyrrolidines as protein-protein interface mimics
Raghuraman, Arjun,Xin, Dongyue,Perez, Lisa M.,Burgess, Kevin
, p. 4823 - 4833 (2013/07/05)
Oligo-pyrrolinone-pyrrolidines (generic structure 1) have the potential to interfere with protein-protein interactions (PPIs), but to reduce this to practice it is necessary to be able to synthesize these structures with a variety of different side chains
Total synthesis, stereochemical assignment, and antimalarial activity of gallinamide A
Conroy, Trent,Guo, Jin T.,Linington, Roger G.,Hunt, Nicholas H.,Payne, Richard J.
supporting information; experimental part, p. 13544 - 13552 (2012/01/13)
The total synthesis and stereochemical assignment of gallinamideA, an antimalarial depsipeptide of cyanobacterial origin, is described. Synthesis of the four possible N-terminal diastereoisomers of gallinamideA (including the natural product symplostatin4) was achieved using a divergent strategy from a common imide fragment. The natural product and corresponding diastereoisomers were synthesized in 30-33% overall yield in a longest linear sequence of 8 steps. Comparative NMR spectroscopic studies of the four synthetic diastereoisomers with the isolated natural product demonstrated that gallinamideA possesses a dimethylated L-isoleucyl residue at the N-terminus. As such, we have shown that gallinamideA is structurally and stereochemically identical to symplostatin4. GallinamideA and its N-terminal diastereoisomers were also shown to possess significant antimalarial activity with IC 50 values in the nanomolar range against the 3D7 strain of Plasmodium falciparum. Naturally active: The total synthesis of gallinamideA, a cyanobacterium-derived depsipeptide, is described. Four N-terminal diastereoisomers of gallinamide A were prepared by using two key fragments (see scheme). Spectroscopic comparison to the isolated natural product enabled the absolute configuration of the N,N-dimethylated isoleucyl residue to be determined as 25S, 26S. GallinamideA (and its diastereoisomers) were also shown to possess potent antimalarial activity. Copyright
Total synthesis and antimalarial activity of symplostatin 4
Conroy, Trent,Guo, Jin T.,Hunt, Nicholas H.,Payne, Richard J.
supporting information; experimental part, p. 5576 - 5579 (2011/04/15)
The first total synthesis of symplostatin 4, a marine cyanobacterium- derived natural product, is described. Notable features of the route include the efficient preparation of three key fragments and final assembly to the natural product via sequential imide and amide couplings. Symplostatin 4 was also demonstrated to possess significant antimalarial activity (ED50 of 74 nM against Plasmodium falciparum, strain 3D7).
FUSED BENZENE DERIVATIVE AND USE
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Page/Page column 53, (2010/02/12)
The present invention provides a compound represented by the general formula: [wherein Ring A represents an optionally substituted 5- to 8-membered ring, Ring B represents a further optionally substituted 4- to 10-membered ring, Ring C represents a further optionally substituted benzene ring, X1 represents carbon atom, X2 represents a carbon atom, an oxygen atom, etc., W represents a nitrogen atom, etc., Y11 represents a group represented by the formula CR2R3' (wherein R2 represents a hydrogen atom, a cyano group, a nitro group, etc., and R3' represents a hydrogen atom, a cyano group, a nitro group, etc., respectively), Y21 represents a group represented by the formula CR4R5' (wherein R4 represents a hydrogen atom, a cyano group, a nitro group, etc., and R5' represents a hydrogen atom, a cyano group, a nitro group, etc., respectively), etc., and R1 represents an electron-withdrawing group, respectively. The formula represents a single bond or a double bond] or a salt thereof, which is useful as an androgen receptor modulator.
A facile solid phase synthesis of tetramic acid
Liu, Zhanxiang,Ruan, Xiuxiu,Huang, Xian
, p. 2505 - 2507 (2007/10/03)
The condensation of N-acylated amino acids with polymer-supported cyclic malonic acid ester was carried out in the presence of DCC/DMAP. The cyclisation of the intermediate resin, by heating in an organic solvent, gave the N-protected tetramic acid derivatives in good yields and high purity.
