Month: November 2022

Louvel, Julien published the artcileAgonists for the Adenosine A₁ Receptor with Tunable Residence Time. A Case for Nonribose 4-Amino-6-aryl-5-cyano-2-thiopyrimidines, Formula: C5H10N2OS, the publication is Journal of Medicinal Chemistry (2014), 57(8), 3213-3222, database is CAplus and MEDLINE.

The synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A₁ receptor (hA₁AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor were described. They show a very diverse range of kinetic profiles (from 1 min (compound I) to 1 h (compound II)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, i.e., the potential elimination of slightly less active compounds that may display preferable binding kinetics.

Journal of Medicinal Chemistry published new progress about 14294-10-1. 14294-10-1 belongs to amides-buliding-blocks, auxiliary class Morpholine,Thiourea,Amine,Amide, name is Morpholine-4-carbothioamide, and the molecular formula is C5H10N2OS, Formula: C5H10N2OS.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wei, BinQing published the artcileDiscovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity, Quality Control of 2418-95-3, the publication is Journal of Medicinal Chemistry (2018), 61(3), 989-1000, database is CAplus and MEDLINE.

Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncol., with three approved by the FDA and over 60 others in clin. trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.

Journal of Medicinal Chemistry published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C7H8BNO4, Quality Control of 2418-95-3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Kabes, Connor Q. published the artcileSyntheses of enantiopure 1,2-ethylenediamines with tethered secondary amines of the formula H₂NCH₂CH[(CH₂)_nNHMe]NH₂ (n = 1 – 4) from α-amino acids: New agents for asymmetric catalysis, Category: amides-buliding-blocks, the publication is Synthesis (2020), 52(21), 3277-3285, database is CAplus.

Tris(hydrochloride) adducts of the title compounds are prepared from the inexpensive α-amino acids H₂N(C:O)CH₂CH(NH₂)CO₂H, HO(C:O)(CH₂)_nCH(NH ₂)CO ₂H (n = 1, 2), and H₂N(CH₂)₄CH(NH₂)CO₂H, resp. (steps/overall yield = 5/32%, 7/30%, 7/33%, 5/38%). The NH₂ group that is remote from the secondary amine is installed via BH₃ reduction of an amide [(C=O)NR₂] derived from an α-amino carboxylic acid. The MeNHCH₂ units are introduced by BH₃ reductions of alkyl carbamate [RO(C:O)NHCH₂; R = Et, t-Bu] or amide [MeHN(C:O)] moieties.

Synthesis published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C11H22N2O4, Category: amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Pryyma, Alla published the artcileRapid, high-yielding solid-phase synthesis of cathepsin-B cleavable linkers for targeted cancer therapeutics, COA of Formula: C21H33N5O7, the publication is Bioconjugate Chemistry (2020), 31(12), 2685-2690, database is CAplus and MEDLINE.

Antibody-drug conjugates (ADCs) constitute an emerging class of anticancer agents that deliver potent payloads selectively to tumors while avoiding systemic toxicity associated with conventional chemotherapeutics. Critical to ADC development is a serum-stable linker designed to decompose inside targeted cells thereby releasing the toxic payload. A protease-cleavable linker comprising a valine-citrulline (Val-Cit) motif has been successfully incorporated into three FDA-approved ADCs and is found in numerous preclin. candidates. Herein, we present a high-yielding and facile synthetic strategy for a Val-Cit linker that avoids extensive protecting group manipulation and laborious chromatog. associated with previous syntheses and provides yields that are up to 10-fold higher than by standard methods. This method is easily scalable and takes advantage of cost-effective coupling reagents and high loading 2-chlorotrityl chloride (2-CTC) resin. Modularity allows for introduction of various conjugation handles in final stages of the synthesis. Facile access to such analogs serves to expand the repertoire of available enzymically cleavable linkers for ADC generation. This methodol. empowers a robust and facile library generation and future exploration into linker analogs containing unnatural amino acids as a selectivity tuning tool.

Bioconjugate Chemistry published new progress about 916746-27-5. 916746-27-5 belongs to amides-buliding-blocks, auxiliary class ADC Linker,Enzymatic Cleavage Linker, name is (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, and the molecular formula is C21H33N5O7, COA of Formula: C21H33N5O7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Putta, V. P. Rama Kishore published the artcileThe facile and efficient organocatalytic platform for accessing 1,2,4-selenadiazoles and thiadiazoles under aerobic conditions, SDS of cas: 64559-06-4, the publication is Tetrahedron Letters (2018), 59(10), 904-908, database is CAplus.

The organocatalytic approach towards synthesis of rarely explored 1,2,4-selenadiazole and thiadiazole scaffolds have been devised using corresponding carboxamides as substrates. The transformations were realized using two distinct conditions in the presence of catalytic vitamin B₃ or thiourea under aerobic conditions. Developed methods overcome the associated limitations of previous reported approaches and the desired products were obtained in high yields and selectivity without the formation of toxic side-products.

Tetrahedron Letters published new progress about 64559-06-4. 64559-06-4 belongs to amides-buliding-blocks, auxiliary class Amine,Benzene,Amide,Ether, name is 3-Methoxybenzothioamide, and the molecular formula is C8H9NOS, SDS of cas: 64559-06-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Xu, Xiaolei published the artcileReactivity of chloroacetamides toward sulfide + black carbon: Insights from structural analogues and dynamic NMR spectroscopy, Recommanded Product: 2-Chloroacetamide, the publication is Science of the Total Environment (2022), 150064, database is CAplus and MEDLINE.

Chloroacetamides are commonly used in herbicide formulations, and their occurrence has been reported in soils and groundwater. However, how their chem. structures affect transformation kinetics and pathways in the presence of environmental reagents such as hydrogen sulfide species and black carbon has not been investigated. In this work, we assessed the impact of increasing Cl substituents on reaction kinetics and pathways of six chloroacetamides. The contribution of individual pathways (reductive dechlorination vs. nucleophilic substitution) to the overall decay of selected chloroacetamides was differentiated using various exptl. setups; both the transformation rates and product distributions were characterized. Our results suggest that the number of Cl substituents affected reaction pathways and kinetics: trichloroacetamides predominantly underwent reductive dechlorination whereas mono- and dichloroacetamides transformed via nucleophilic substitution. Furthermore, we synthesized eight dichloroacetamide analogs (Cl2CHC(=O)NRR′) with differing R groups and characterized their transformation kinetics. Dynamic NMR spectroscopy was employed to quantify the rotational energy barriers of dichloroacetamides. Our results suggest that adsorption of dichloroacetamides on black carbon constrained R groups from approaching the dichloromethyl carbon and subsequently favored nucleophilic attack. This study provides new insights to better predict the fate of chloroacetamides in subsurface environments by linking their structural characteristics to transformation kinetics and pathways.

Science of the Total Environment published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C19H17N2NaO4S, Recommanded Product: 2-Chloroacetamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Bhukya, Bhadru published the artcileSynthesis and anticancer activity of novel oxadiazole functionalized pyrazolo[3,4-b]pyridine derivatives, Recommanded Product: 2-Chloroacetamide, the publication is Asian Journal of Chemistry (2021), 33(6), 1331-1335, database is CAplus.

A series of novel oxadiazole functionalized pyrazolo[3,4-b]pyridine derivatives I (R = Ph, thien-2-yl; R¹ = C₆H₅, 3-CH₃C₆H₄, 3-FC₆H₄, etc.) was synthesized using 6-thiophenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine through reaction with 2-bromoethyl acetate, followed by hydrazine hydrate to afford hydrazide derivatives II (R = Ph, thien-2-yl). These compounds were further treated with aromatic acids in the presence of phosphoryl chloride and obtained oxadiazole functionalized pyrazolo[3,4-b]pyridine derivatives I. All the synthesized compounds I were screened for anticancer activity against four cancer cell lines such as HeLa – cervical cancer (CCL-2); COLO 205-colon cancer (CCL-222); HepG2-liver cancer (HB-8065); MCF7-breast cancer (HTB-22). Compounds I (R = thien-2-yl; R¹ = 3-FC₆H₄), I (R = thien-2-yl; R¹ = 3-MeOC₆H₄) and I (R = thien-2-yl; R¹ = 3-F₃CC₆H₄) were found to have more prominent anticancer activity at micromolar concentration

Asian Journal of Chemistry published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C2H4ClNO, Recommanded Product: 2-Chloroacetamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Hao, Qi published the artcileMesenchymal stem cell-derived extracellular vesicles decrease lung injury in mice, Safety of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Journal of Immunology (2019), 203(7), 1961-1975, database is CAplus and MEDLINE.

Human mesenchymal stem cell (MSC) extracellular vesicles (EV) can reduce the severity of bacterial pneumonia, but little is known about the mechanisms underlying their antimicrobial activity. In the current study, we found that bacterial clearance induced by MSC EV in Escherichia coli pneumonia in C57BL/6 mice was associated with high levels of leukotriene (LT) B₄ in the injured alveolus. More importantly, the antimicrobial effect of MSC EV was abrogated by cotreatment with a LTB₄ BLT1 antagonist. To determine the role of MSC EV on LT metabolism, we measured the effect of MSC EV on a known ATP-binding cassette transporter, multidrug resistance-associated protein 1 (MRP1), and found that MSC EV suppressed MRP1 mRNA, protein, and pump function in LPS-stimulated Raw264.7 cells in vitro. The synthesis of LTB₄ and LTC₄ from LTA₄ are competitive, and MRP1 is the efflux pump for LTC₄. Inhibition of MRP1 will increase LTB₄ production In addition, administration of a nonspecific MRP1 inhibitor (MK-571) reduced LTC₄ and subsequently increased LTB₄ levels in C57BL/6 mice with acute lung injury, increasing overall antimicrobial activity. We previously found that the biol. effects of MSC EV were through the transfer of its content, such as mRNA, microRNA, and proteins, to target cells. In the current study, miR-145 knockdown abolished the effect of MSC EV on the inhibition of MRP1 in vitro and the antimicrobial effect in vivo. In summary, MSC EV suppressed MRP1 activity through transfer of miR-145, thereby resulting in enhanced LTB₄ production and antimicrobial activity through LTB₄/BLT1 signaling.

Journal of Immunology published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Safety of [(2-Hexylcyclopentylidene)amino]thiourea.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Zahariev, Sotir published the artcileSolvent-free synthesis of azole carboximidamides, Product Details of C15H14N2, the publication is Tetrahedron Letters (2004), 45(51), 9423-9426, database is CAplus.

A one-pot procedure is described for the preparation of 1H-pyrazole-carboximidamides, 1H-benzotriazole-carboximidamides and guanidinylation of amines with 1H-benzotriazole-carboximidamides. The X-ray crystal structure of N,N-dimethyl-1H-benzotriazole-1-carboximidamide (I), has been determined The reaction of 1H-benzotriazole hydrochloride with N,N-dimethylcyanamide to give I (in situ) was followed by addition of N²-[(phenylmethoxy)carbonyl]-L-ornithine (II) under microwave irradiation conditions. This reaction yielded the corresponding guanidine derivative, i.e., N²-tert-butoxycarbonyl-N^G,N^G-dimethyl-L-arginine (III).

Tetrahedron Letters published new progress about 2451-91-4. 2451-91-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Benzene, name is N,N-Dibenzylcyanamide, and the molecular formula is 0, Product Details of C15H14N2.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

MacCallum, Stephanie F. published the artcileDysregulation of autophagy in chronic lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Scientific Reports (2013), 1275, 8 pp., database is CAplus and MEDLINE.

Tenovin-6 (Tnv-6) is a bioactive small mol. with anti-neoplastic activity. Inhibition of the Sirtuin class of protein deacetylases with activation of p53 function is associated with the pro-apoptotic effects of Tnv-6 in many tumors. Here, we demonstrate that in chronic lymphocytic leukemia (CLL) cells, Tnv-6 causes non-genotoxic cytotoxicity, without adversely affecting human clonogenic hematopoietic progenitors in vitro, or murine hematopoiesis. Mechanistically, exposure of CLL cells to Tnv-6 did not induce cellular apoptosis or p53-pathway activity. Transcriptomic profiling identified a gene program influenced by Tnv-6 that included autophagy-lysosomal pathway genes. The dysregulation of autophagy was confirmed by changes in cellular ultrastructure and increases in the autophagy-regulatory proteins LC3 (LC3-II) and p62/Sequestosome. Adding bafilomycin-A1, an autophagy inhibitor to Tnv-6 containing cultures did not cause synergistic accumulation of LC3-II, suggesting inhibition of late-stage autophagy by Tnv-6. Thus, in CLL, the cytotoxic effects of Tnv-6 result from dysregulation of protective autophagy pathways.

Scientific Reports published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics