Tag: M.W=400-450

Onda, Yuichi published the artcileConformation-based design and synthesis of apratoxin A mimetics modified at the α,β-unsaturated thiazoline moiety, COA of Formula: C25H23NO4, the publication is Journal of Medicinal Chemistry (2017), 60(15), 6751-6765, database is CAplus and MEDLINE.

We have demonstrated design, synthesis, and biol. evaluation of apratoxin A mimetics. In the first generation, the moCys moiety was replaced with seven simple amino acids as their 3D structures can be similar to that of apratoxin A. Apratoxins M1-M7 were synthesized using solid-phase peptide synthesis and solution-phase macrolactamization. Apratoxin M7, which contains a piperidinecarboxylic acid moiety, exhibited potent cytotoxicity against HCT-116 cells. In the second generation, substitution of each amino acid residue in the tripeptide Tyr(Me)-MeAla-MeIle moiety in apratoxin M7 led to the development of the highly potent apratoxin M16 possessing biphenylalanine (Bph) instead of Tyr(Me), which exhibited an IC₅₀ value of 1.1 nM against HCT-116 cells. Moreover, compared to apratoxin A, apratoxin M16 exhibited a similarly high level of growth inhibitory activity against various cancer cell lines. The results indicate that apratoxin M16 could be a potential candidate as an anticancer agent.

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, COA of Formula: C25H23NO4.

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

De Prins, An published the artcileSynthesis and in vitro evaluation of stabilized and selective neuromedin U-1 receptor agonists, SDS of cas: 77128-73-5, the publication is ACS Medicinal Chemistry Letters (2018), 9(5), 496-501, database is CAplus and MEDLINE.

Neuromedin U (NMU) is a multifunctional neuropeptide which is characterized by a high conservation through all species. Herein, we describe the synthesis of a novel set of NMU-analogs based on the truncated NMU-8. Through combination of previously reported modifications, an elaborate structure-activity relationship study was performed aiming for the development of peptides with an increased selectivity toward NMU receptor 1 (NMUR1). Compound (Ac-Dmt-Phe-Leu-Dmt-Arg-Pro-Arg-Asn-NH₂) possessed the highest NMUR1 selectivity (IC₅₀ = 0.54 nM, selectivity ratio = 5313) together with an increased potency (EC₅₀ = 3.7 nM), an 18% increase of the maximal effect at NMUR1, and a higher resistance against enzymic degradation as compared to the native NMU-8. The development of a potent NMUR1 agonist with extended half-life could represent an attractive tool to further unveil the role of NMUR1 in NMU signaling.

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, SDS of cas: 77128-73-5.

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

Kurnia, Dessy Yulyani published the artcileTotal synthesis of xylapeptide B [Cyclo-( L-Leu-L-Pro-N-Me-Phe-L-Val-D-Ala )], Application of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Journal of Heterocyclic Chemistry (2022), 59(1), 131-136, database is CAplus.

Xylapeptide B is a cyclopentapeptide isolated from Xylaria sp. derived from the Chinese medicinal plant Sophora tonkinensis. Xylapeptide B was successfully synthesized by a combination of solid- and solution-phase, using the Fmoc (Fmoc = 9-fluorenylmethoxycarbonyl) strategy, and 2-chlorotrityl chloride resin. The coupling reagent used is a combination of HBTU/HOBt to assist in the formation of amide bonds. D-Ala was chosen as the C-terminal because it has a small residue and can facilitate the cyclization process. Linear peptide was cleaved from the resin using a dilute acid concentration of 20% TFA in DCM because the peptide has no protecting group at the side chain. Crude linear peptide was purified by semi-preparative RP-HPLC using 0%-100% ACN eluent for 35 min and obtained a pure mass of 22.4 mg (18.83%). Cyclization was carried out in solution phase using HBTU (3 equivalent) and DIPEA (1% volume/volume) in diluted concentration (1.25 mM) for 72 h at room temperature The cyclization stage was monitored by thin-layer chromatog. (TLC). Crude xylapeptide B was purified by semi-preparative RP-HPLC using 30%-80% ACN eluent for 40 min, to result in 6 mg (8.91%) of the desired xylapeptide B. All synthesized products were characterized by HR-TOFMS, ¹H-, and ¹³C-NMR.

Journal of Heterocyclic 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, Application 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

Nielsen, Daniel S. published the artcileHigh Cell Permeability Does Not Predict Oral Bioavailability for Analogues of Cyclic Heptapeptide Sanguinamide A*, Category: ethers-buliding-blocks, the publication is Australian Journal of Chemistry (2020), 73(4), 344-351, database is CAplus.

The cyclic heptapeptide derivative, sanguinamide A, is a model scaffold for studying how component amino acids, heterocycles, and N-methylation influence membrane permeability and oral bioavailability. Membrane permeable sanguinamide A analogs have been reported, but there is limited data on their pharmacokinetic properties in vivo. Here we report pharmacokinetic properties for highly cell and membrane permeable sanguinamide A analogs in rats and find that there is no correlation between reported permeability in vitro and oral bioavailability in vivo. We show that N-methylation of sanguinamide A analogs gives compounds with greater flexibility, greater susceptibility to degradation by rat liver microsomes, and lower oral bioavailability in rats.

Australian Journal of 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, Category: ethers-buliding-blocks.

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

Stephens, Thomas C. published the artcileSynthesis of cyclic peptide mimetics by the successive ring expansion of lactams, Name: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Chemistry – A European Journal (2017), 23(54), 13314-13318, database is CAplus and MEDLINE.

A successive ring-expansion protocol is reported that enables the controlled insertion of natural and non-natural amino acid fragments into lactams. Amino acids can be installed into macrocycles via an operationally simple and scalable iterative procedure, without the need for high dilution This method is expected to be of broad utility, especially for the synthesis of medicinally important cyclic peptide mimetics.

Chemistry – A European Journal 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 C8H15NO, Name: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid.

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

Lefever, Mark published the artcileStructural Requirements for CNS Active Opioid Glycopeptides, Category: ethers-buliding-blocks, the publication is Journal of Medicinal Chemistry (2015), 58(15), 5728-5741, database is CAplus and MEDLINE.

Glycopeptides related to β-endorphin penetrate the blood-brain barrier (BBB) of mice to produce antinociception. Two series of glycopeptides were assessed for opioid receptor binding affinity. Attempts to alter the mu-selectivity of [D-Ala²,N-MePhe⁴,Gly-ol⁵]enkephalin (DAMGO)-related glycopeptides by altering the charged residues of the amphipathic helical address were unsuccessful. A series of pan-agonists was evaluated for antinociceptive activity (55 °C tail flick) in mice. A flexible linker was required to maintain antinociceptive activity. CD in H₂O, trifluoroethanol (TFE), and SDS micelles confirmed the importance of the amphipathic helixes (11s â†?11sG â†?11) for antinociception. The glycosylated analogs showed only nascent helixes and random coil conformations in H₂O. Chem. shift indexes (CSI) and nuclear Overhauser effects (NOE) with 600 MHz NMR and CD confirmed helical structures in micelles, which were rationalized by mol. dynamics calculations Antinociceptive studies with mice confirm that these glycosylated endorphin analogs are potential drug candidates that penetrate the BBB to produce potent central effects.

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, Category: ethers-buliding-blocks.

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

Spencer, Ryan K. published the artcileX-ray Crystallographic Structures of Trimers and Higher-Order Oligomeric Assemblies of a Peptide Derived from Aβ_17-36, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Journal of the American Chemical Society (2014), 136(15), 5595-5598, database is CAplus and MEDLINE.

A peptide derived from Aβ_17-36 crystallizes to form trimers that further associate to form higher-order oligomers. The trimers consist of three highly twisted β-hairpins in a triangular arrangement. Two trimers associate face-to-face in the crystal lattice to form a hexamer; four trimers in a tetrahedral arrangement about a central cavity form a dodecamer. These structures provide a working model for the structures of oligomers associated with neurodegeneration in Alzheimer’s disease.

Journal of the American Chemical Society 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 C8H7ClO3, 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

Hall, Sara M. published the artcileDiscovery of Stable Non-opioid Dynorphin A Analogues Interacting at the Bradykinin Receptors for the Treatment of Neuropathic Pain, Product Details of C25H23NO4, the publication is ACS Chemical Neuroscience (2016), 7(12), 1746-1752, database is CAplus and MEDLINE.

Dynorphin A (Dyn A) is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors with a preference for the kappa receptor but also neuroexcitatory effects, which cause hyperalgesia. We have shown that the neuroexcitatory effects are mediated through bradykinin (BK) receptors and that intrathecal (i.th.) administration of our lead ligand 1, [des-Arg⁷]-Dyn A-(4-11), which shows good binding affinity (IC₅₀ = 150 nM) at the BK receptors, blocks Dyn A-induced hyperalgesia in naïve animals and reverses thermal and tactile hypersensitivities in a dose-dependent manner in nerve-injured animals. However, 1 has a serious drawback as a potential drug candidate for the treatment of neuropathic pain because of its susceptibility to enzymic degradation In an effort to increase its stability, we modified ligand 1 using non-natural amino acids and found that analogs substituted at or near the N-terminus with a D-isomer retain binding at the receptor and provide a large increase in stability. In particular when Leu⁵ was modified, with either the D-isomer or N-methylation, there was a large increase in stability (t_1/2 = 0.7-160 h in rat plasma) observed From these studies, we have developed a very stable Dyn A analog 16, [D-Leu⁵,des-Arg⁷]-Dyn A-(4-11), that binds to BK receptors (IC₅₀ = 130 nM) in the same range as ligand 1 and shows good antihyperalgesic effects in both naïve rats and L₅/L₆ spinal nerve ligation rats.

ACS Chemical Neuroscience 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

Phelan, James P. published the artcileOpen-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis, Formula: C25H23NO4, the publication is Journal of the American Chemical Society (2019), 141(8), 3723-3732, database is CAplus and MEDLINE.

DNA-encoded library (DEL) technol. is a powerful tool commonly used by the pharmaceutical industry for the identification of compounds with affinity to biomol. targets. Success in this endeavor lies in sampling diverse chem. libraries. However, current DELs tend to be deficient in C(sp³) carbon counts. The authors report unique solutions to the challenge of increasing both the chem. diversity of these libraries and their C(sp³) carbon counts by merging Ni/photoredox dual catalytic C(sp²)-C(sp³) cross-coupling as well as photoredox-catalyzed radical/polar crossover alkylation protocols with DELs. The successful integration of multiple classes of radical sources enables the rapid incorporation of a diverse set of alkyl fragments.

Journal of the American Chemical Society 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, Formula: C25H23NO4.

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

Sekiguchi, Haruka published the artcileStructure-activity relationship study of cyclic pentapeptide ligands for atypical chemokine receptor 3 (ACKR3), Related Products of ethers-buliding-blocks, the publication is Journal of Medicinal Chemistry (2018), 61(8), 3745-3751, database is CAplus and MEDLINE.

The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiol. and pathol. processes. Here, we investigated the SAR of the component amino acids in an ACKR3-selective ligand, FC313 [cyclo(-D-Tyr-L-Arg-L-MeArg-L-Nal(2)-L-Pro-)], for the development of highly active ACKR3 ligands. Notably, modification at the L-Pro position with a bulky hydrophobic side chain led to improved bioactivity toward ACKR3.

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 C22H18O2, Related Products of ethers-buliding-blocks.

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