Tag: M.W=400-450

Boeglin, Joel published the artcileDevelopment of a practical solid-phase synthesis approach to 1,3,5-triazepan-2,6-diones, Category: ethers-buliding-blocks, the publication is Tetrahedron (2012), 68(36), 7472-7478, database is CAplus.

1,3,5-Triazepan-2,6-diones are a class of conformationally restricted heterocycles derived from dipeptides. With the aim to develop a general and practical method useful for library production, three polymer-assisted syntheses, all based on a catch and release approach, have been evaluated and compared. The method involving a Hofmann rearrangement of N-Boc dipeptide carboxamides and subsequent trapping of the isocyanate on polymer-supported N-hydroxysuccinimide (PS-HOSu) was found to be the most reliable and versatile, allowing rapid access to the 1,3,5-triazepan-2,6-dione skeleton.

Tetrahedron published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Category: ethers-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Yan, Li-Mei published the artcileSelectively N-Methylated Soluble IAPP Mimics as Potent IAPP Receptor Agonists and Nanomolar Inhibitors of Cytotoxic Self-Assembly of Both IAPP and Aβ40, Product Details of C25H23NO4, the publication is Angewandte Chemie, International Edition (2013), 52(39), 10378-10383, database is CAplus and MEDLINE.

The aggregation of islet amyloid polypeptide (IAPP) is linked to β-cell degeneration and the pathogenesis of type 2 diabetes (T2D). IAPP is a 37-residue polypeptide hormone secreted by the pancreatic β-cells. IAPP amyloid deposits are found in the pancreata of many T2D patients. In its soluble form, however, IAPP acts as a brain-gut neuropeptide regulator of glucose homeostasis. Here we show that selectively N-methylated soluble IAPP mimics as potent IAPP receptor agonists and nanomolar inhibitors of cytotoxic self-assembly of both IAPP and Aβ40.

Angewandte Chemie, International Edition published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C5H9IO2, Product Details of C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Hayashi, Kyohei published the artcileMacrocyclic Peptides as a Novel Class of NNMT Inhibitors: A SAR Study Aimed at Inhibitory Activity in the Cell, Product Details of C25H23NO4, the publication is ACS Medicinal Chemistry Letters (2021), 12(7), 1093-1101, database is CAplus and MEDLINE.

Nicotinamide N-methyltransferase (NNMT), which catalyzes the methylation of nicotinamide, is a cytosolic enzyme that has attracted much attention as a therapeutic target for a variety of diseases. However, despite the considerable interest in this target, reports of NNMT inhibitors have still been limited to date. In this work, utilizing in vitro translated macrocyclic peptide libraries, we identified peptide 1 as a novel class of NNMT inhibitors. Further exploration based on the X-ray cocrystal structures of the peptides with NNMT provided a dramatic improvement in inhibitory activity (peptide 23: IC₅₀ = 0.15 nM). Furthermore, by balance of the peptides’ lipophilicity and biol. activity, inhibitory activity against NNMT in cell-based assay was successfully achieved (peptide 26: cell-based IC₅₀ = 770 nM). These findings illuminate the potential of cyclic peptides as a relatively new drug discovery modality even for intracellular targets.

ACS Medicinal Chemistry Letters published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Product Details of C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Marcucci, Eleonora published the artcileSolid-Phase Synthesis of NMe-IB-01212, a Highly N-Methylated Cyclic Peptide, Related Products of ethers-buliding-blocks, the publication is Organic Letters (2012), 14(2), 612-615, database is CAplus and MEDLINE.

N-Methylation of peptides is an important synthetic tool in peptide-based medicinal chem. Herein, an optimized strategy for solid-phase synthesis of small but highly N-methylated cyclic peptides is described. The proposed route addresses several problems associated with the synthesis of peptides containing several sequential N-methyl-amino acids, such as in situ N-methylation, difficulty of acylation, epimerization, diketopiperazine formation, and stability at the NMe sites under trifluoroacetic acid exposure. The resulting NMe-IB-01212 exhibits micromolar activity and considerable stability.

Organic Letters published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Related Products of ethers-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Barnash, Kimberly D. published the artcileDiscovery of Peptidomimetic Ligands of EED as Allosteric Inhibitors of PRC2, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is ACS Combinatorial Science (2017), 19(3), 161-172, database is CAplus and MEDLINE.

The function of EED within Polycomb repressive complex 2 (PRC2) is mediated by a complex network of protein-protein interactions. Allosteric activation of PRC2 by binding of methylated proteins to EED’s aromatic cage is essential for full catalytic activity, but details of this regulation are not fully understood. EED’s recognition of the product of PRC2 activity, histone H3 lysine 27 trimethylation (H3K27me3), stimulates PRC2 methyltransferase activity at adjacent nucleosomes leading to H3K27me3 propagation and, ultimately, gene repression. By coupling combinatorial chem. and structure-based design, we optimized a low affinity methylated Jarid2 peptide to a smaller, more potent peptidomimetic ligand (Kd = 1.14 ± 0.14 μM) of the aromatic cage of EED. Our strategy illustrates the effectiveness of applying combinatorial chem. to achieve both ligand potency and property optimization. Furthermore, the resulting ligands, UNC5114 and UNC5115, demonstrate that targeted disruption of EED’s reader function can lead to allosteric inhibition of PRC2 catalytic activity.

ACS Combinatorial Science published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Masuda, Yuichi published the artcileSystematic Analysis of the Relationship among 3D Structure, Bioactivity, and Membrane Permeability of PF1171F, a Cyclic Hexapeptide with Paralyzing Effects on Silkworms, SDS of cas: 77128-73-5, the publication is Journal of Organic Chemistry (2017), 82(21), 11447-11463, database is CAplus and MEDLINE.

PF1171 hexapeptides, a family of cyclic hexapeptides produced by fungi, exhibit paralyzing effects on the larvae of silkworms via oral administration. To elucidate the structural features of PF1171 hexapeptides that are crucial for bioactivity, the relationship among 3D structure, bioactivity, and membrane permeability of PF1171F (the peptide with the highest bioavailability) was systematically analyzed through the synthesis of 22 analogs. The PF1171F analogs were prepared by the solid-phase synthesis of a linear precursor and subsequent solution-phase macrolactamization. Anal. by NMR spectroscopy and mol. modeling indicated that the major 3D conformations of PF1171F in various solvents resemble its x-ray crystal structure. The analogs with this conformation tend to exhibit potent paralysis against silkworms, indicating the significance of the conformation in the paralysis. The biol. activity was dependent on the mode of administration, varying between hemolymph injection and oral administration. Parallel artificial membrane permeability assay (PAMPA) of the analogs revealed a correlation between membrane permeabilities and paralytic activity by hemolymph injection, indicating that the target mol. of PF1171F is present inside the cell membrane.

Journal of Organic Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, SDS of cas: 77128-73-5.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Kitamura, Takashi published the artcileDesign of coibamide A mimetics with improved cellular bioactivity, Synthetic Route of 77128-73-5, the publication is ACS Medicinal Chemistry Letters (2022), 13(1), 105-110, database is CAplus and MEDLINE.

Coibamide A, a cyclic depsipeptide isolated from a Panamanian marine cyanobacterium, shows potent cytotoxic activity via the inhibition of the Sec61 translocon. We designed a coibamide A mimetic in which the ester linkage between MeThr and D-MeAla in coibamide A was replaced with an alkyl linker to provide a stable macrocyclic scaffold possessing a MeLys(Me) residue. Taking advantage of a facile solid-phase synthetic approach, an structure-activity relationship (SAR) study of the newly designed macrocyclic structure was performed, with a focus on altering the pattern of N-Me substitution and amino acid configurations. Overall, the simplified macrocyclic scaffold with an alkyl linker resulted in a significantly reduced cytotoxicity. Instead, more potent coibamide A derivatives with a β-(4-biphenylyl)alanine (Bph) group were identified after the optimization of the Tyr(Me) position in the original macrocyclic scaffold of coibamide A based on the characteristic apratoxin A substructures. The similar SAR between coibamide A and apratoxin A suggests that the binding site of the Tyr(Me) side chain at the luminal end of Sec61α may be shared.

ACS Medicinal Chemistry Letters published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Synthetic Route of 77128-73-5.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Tal-Gan, Yftah published the artcileN-Methyl and peptoid scans of an autoinducing peptide reveal new structural features required for inhibition and activation of AgrC quorum sensing receptors in Staphylococcus aureus, COA of Formula: C25H23NO4, the publication is Chemical Communications (Cambridge, United Kingdom) (2014), 50(23), 3000-3003, database is CAplus and MEDLINE.

We report the first N-Me and peptoid residue scans of a full-length autoinducing peptide (AIP), AIP-III, used by Staphylococcus aureus for quorum sensing (QS). Biol. evaluation of these AIP-III analogs uncovered new features of the AIP-III scaffold that can be tuned to develop chem. probes of QS in all four groups of S. aureus (I-IV).

Chemical Communications (Cambridge, United Kingdom) published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C4H11NO, COA of Formula: C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Kreutzer, Adam G. published the artcileA Hexamer of a Peptide Derived from Aβ_16-36, Related Products of ethers-buliding-blocks, the publication is Biochemistry (2017), 56(45), 6061-6071, database is CAplus and MEDLINE.

The absence of high-resolution structures of amyloid oligomers constitutes a major gap in our understanding of amyloid diseases. Increasing evidence indicates that oligomers of the β-amyloid peptide Aβ are especially important in the progression of Alzheimer’s disease. In many Aβ oligomers, the Aβ monomer components are thought to adopt a β-hairpin conformation. This paper describes the design and study of a macrocyclic β-hairpin peptide derived from Aβ16-36. SDS-PAGE and size exclusion chromatog. studies show that the Aβ16-36 β-hairpin peptide assembles in solution to form hexamers, trimers, and dimers. X-ray crystallog. reveals that the peptide assembles to form a hexamer in the crystal state and that the hexamer is composed of dimers and trimers. LDH release assays show that the oligomers formed by the Aβ16-36 β-hairpin peptide are toxic toward neuronally derived SH-SY5Y cells. Replica-exchange mol. dynamics (REMD) demonstrates that the hexamer can accommodate full-length Aβ. These findings expand our understanding of the structure, solution-phase behavior, and biol. activity of Aβ oligomers, and may offer insights into the mol. basis of Alzheimer’s disease.

Biochemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Related Products of ethers-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Fransson, Rebecca published the artcileConstrained H-Phe-Phe-NH₂ Analogues with High Affinity to the Substance P 1-7 Binding Site and with Improved Metabolic Stability and Cell Permeability, Product Details of C25H23NO4, the publication is Journal of Medicinal Chemistry (2013), 56(12), 4953-4965, database is CAplus and MEDLINE.

The authors recently reported the discovery of H-Phe-Phe-NH₂ as a small and high affinity ligand for the substance P 1-7 (SP_1-7, H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) specific binding site and its intriguing ability to reduce neuropathic pain. With the overall aim to develop stable and orally bioavailable SP_1-7 mimetics, the dipeptide was chosen as a lead compound Herein the structure-activity relationship (SAR) of a set of modified H-Phe-Phe-NH₂ analogs is presented together with their potential active uptake by PEPT1 transporter, intestinal permeability, and metabolic stability. Local constraints via peptide backbone methylation or preparation of cyclized analogs based on pyrrolidine were evaluated and were shown to significantly improve the in vitro pharmacokinetic properties. The SAR was rationalized by deriving a plausible binding pose for the high affinity ligands. Rigidification using a 3-phenylpyrrolidine moiety in the C-terminal of H-Phe-Phe-NH₂ resulted in high affinity and improved intrinsic clearance and intestinal epithelial permeability.

Journal of Medicinal Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Product Details of C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem