185304-19-2Relevant academic research and scientific papers
ARGINASE INHIBITORS AND METHODS OF USE THEREOF
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, (2019/09/04)
Disclosed are compounds of formula (Ia) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ia) and methods of using the same for treating cancer or a respiratory inflammatory disease and inhibiting arginase, wherein R1 is -NHR1a; R1a is -H or -C(O)CH(R1b)NHR1c; and R1b is selected from -H, -(C1-C4 ) alkyl and CH2OR1d and R1cis -H; or R1b and R1c, together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R1d is H or -CH3.
Discovery of subnanomolar arginine-glycine-aspartate-based αvβ3/αvβ5 integrin binders embedding 4-aminoproline residues
Zanardi, Franca,Burreddu, Paola,Rassu, Gloria,Auzzas, Luciana,Battistini, Lucia,Curti, Claudio,Sartori, Andrea,Nicastro, Giuseppe,Menchi, Gloria,Cini, Nicoletta,Bottonocetti, Anna,Raspanti, Silvia,Casiraghi, Giovanni
, p. 1771 - 1782 (2008/09/21)
The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity αvβ3/αvβ 5 integrin binders [IC50h(αvβ 3) 0.03-5.12 nM; IC50h(αvβ 5) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the Nα- nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the αvβ3 receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin αvβ3 complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.
Strategies for the solid-phase diversification of poly-L-proline-type II peptide mimic scaffolds and peptide scaffolds through guanidinylation
Flemer, Stevenson,Wurthmann, Alexander,Mamai, Ahmed,Madalengoitia, Jose S.
, p. 7593 - 7602 (2008/12/22)
(Chemical Equation Presented) A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pmc-N′-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH2Cl2 followed by EDCI-mediated reaction of N-Pmc-N′-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.
Design and synthesis of photoaffinity-labeling ligands of the L-prolyl-L-leucylglycinamide binding site involved in the allosteric modulation of the dopamine receptor
Fisher, Abigail,Mann, Amandeep,Verma, Vaneeta,Thomas, Nancy,Mishra, Ram K.,Johnson, Rodney L.
, p. 307 - 317 (2007/10/03)
Pro-Leu-Gly-NH2 (PLG), in addition to its endocrine effects, possesses the ability to modulate dopamine 02 receptors within the central nervous system. However, the precise binding site of PLG is unknown. Potential photoaffinity-labeling ligand
NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
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, (2008/06/13)
The present invention discloses novel peptide compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such peptides as well as methods of using them to treat disorders associated with the HCV protease.
Synthesis of N(α)-(pyrinyl/pyrimidinyl acetyl)-4-aminoproline diastereomers with potential use in PNA synthesis
Gangamani, Bargur P.,Kumar, Vaijayanti A.,Ganesh, Krishna N.
, p. 15017 - 15030 (2007/10/03)
This paper describes an approach to introduce conformational constraint and chirality into the PNA backbone by bridging the ethylenediamine and glycine components of thesame unit by a methylene group which leads to PNA based on 4-aminoprolyl backbone with chirality at C-4 and C-2. The synthesis and characterisation of all four diasteroisomers with thymine (T) as the sidechain nucleobase (3a-d) and the synthesis of one of the stereoisomer (2S, 4R) linked to each of the four nucleobases (10-13) are described. Using these monomeric units, two model dimers (17, 18) containing four chiral centres but differing in stereochemistry at only one site were prepared and CD data on these indicate considerable structural differences in base stacking induced by chiral backbone among these.
