Month: December 2022

Kuljanin, Miljan published the artcileReimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries, Related Products of amides-buliding-blocks, the publication is Nature Biotechnology (2021), 39(5), 630-641, database is CAplus and MEDLINE.

Current methods used for measuring amino acid side-chain reactivity lack the throughput needed to screen large chem. libraries for interactions across the proteome. Here we redesigned the work flow for activity-based protein profiling of reactive cysteine residues by using a smaller desthiobiotin-based probe, sample multiplexing, reduced protein starting amounts and software to boost data acquisition in real time on the mass spectrometer. Our method, streamlined cysteine activity-based protein profiling (SLC-ABPP), achieved a 42-fold improvement in sample throughput, corresponding to profiling library members at a depth of >8,000 reactive cysteine sites at 18 min per compound We applied it to identify proteome-wide targets of covalent inhibitors to mutant Kirsten rat sarcoma (KRAS)^G12C and Bruton’s tyrosine kinase (BTK). In addition, we created a resource of cysteine reactivity to 285 electrophiles in three human cell lines, which includes >20,000 cysteines from >6,000 proteins per line. The goal of proteome-wide profiling of cysteine reactivity across thousand-member libraries under several cellular contexts is now within reach.

Nature Biotechnology 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, Related Products of amides-buliding-blocks.

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

Jha, Deepti published the artcileCyLoP-1: A Novel Cysteine-Rich Cell-Penetrating Peptide for Cytosolic Delivery of Cargoes, Recommanded Product: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, the publication is Bioconjugate Chemistry (2011), 22(3), 319-328, database is CAplus and MEDLINE.

Cell-penetrating peptides (CPPs) may have implications in biomedical sciences by improving the delivery of a wide variety of drugs through the membrane barrier. CPPs are generally taken up by endocytic pathways, and vesicular encapsulation is a limiting factor in the area of intracellular targeting. A novel, cationic cysteine-rich CPP, CyLoP-1, has been developed exhibiting distinguished diffused cytosolic distribution along with endosomal uptake at low micromolar concentrations Comparative uptake anal. with known CPPs showed CyLoP-1 as a promising delivery vector to access the cytosol in a variety of cell types. In addition to the pos. charged residues, the presence of cysteines and tryptophans proved to be essential to maintain its functionality. Also, the oxidation status of the cysteines played an important role for the uptake efficiency of CyLoP-1, with the disulfide-containing form being more effective. The distinct feature of CyLoP-1 to enter the cytosol was further explored by the covalent attachment of cargoes of different nature and sizes. In particular, induction of caspase-3 activity (indicating apoptosis) by a CyLoP-1-SmacN7 conjugate proved successful delivery of the pro-apoptotic cargo to its site of action in the cytosol. Efficient intracellular delivery into the entire cytosol already at low micromolar concentrations makes CyLoP-1 a promising candidate for cytosolic delivery of cargoes of small sizes. Thus, this peptide might prove to be useful for efficient transmembrane delivery of agents directed to cytosolic targets.

Bioconjugate Chemistry published new progress about 186046-83-3. 186046-83-3 belongs to amides-buliding-blocks, auxiliary class Purine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, and the molecular formula is C40H35N7O8, Recommanded Product: 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid.

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

Cohen, Irit published the artcileSunlight assisted direct amide formation via a charge-transfer complex, Name: N,N-Diethylisonicotinamide, the publication is Chemical Communications (Cambridge, United Kingdom) (2017), 53(73), 10128-10131, database is CAplus and MEDLINE.

We report on the use of charge-transfer complexes between amines and carbon tetrachloride, as a novel way to activate the amine for photochem. reactions. This principle is demonstrated in a mild, transition metal free, visible light assisted, dealkylative amide formation from feedstock carboxylic acids and amines. The low absorption coefficient of the complex allows deep light penetration and thus scale(coating process) up to a gram scale.

Chemical Communications (Cambridge, United Kingdom) published new progress about 530-40-5. 530-40-5 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N,N-Diethylisonicotinamide, and the molecular formula is C10H14N2O, Name: N,N-Diethylisonicotinamide.

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

Aizpurua, Jesus M. published the artcileDiscovery of a novel family of FKBP12 “reshapers” and their use as calcium modulators in skeletal muscle under nitro-oxidative stress, Product Details of C11H22N2O4, the publication is European Journal of Medicinal Chemistry (2021), 113160, database is CAplus and MEDLINE.

The hypothesis of rescuing FKBP12/RyR1 interaction and intracellular calcium homeostasis through mol. “reshaping” of FKBP12 was investigated. To this end, novel 4-arylthioalkyl-1-carboxyalkyl-1,2,3-triazoles were designed and synthesized, and their efficacy was tested in human myotubes. A library of 17 compounds (10a-n) designed to dock the FKBP12/RyR1 hot-spot interface contact residues, was readily prepared from free α-amino acids and arylthioalkynes using CuAAC “click” protocols amenable to one-pot transformations in high overall yields and total configurational integrity. To model nitro-oxidative stress, human myotubes were treated with the peroxynitrite donor SIN1, and evidence was found that some triazoles 10 were able to normalize calcium levels, as well as FKBP12/RyR1 interaction. For example, compound 10 b at 150 nM rescued 46% of FKBP12/RyR1 interaction and up to 70% of resting cytosolic calcium levels in human myotubes under nitro-oxidative stress. All compounds 10 analyzed showed target engagement to FKBP12 and low levels of cytotoxicity in vitro. Compounds 10b, 10c, 10h, and 10iR were identified as potential therapeutic candidates to protect myotubes in muscle disorders with underlying nitro-oxidative stress, FKBP12/RyR1 dysfunction and calcium dysregulation.

European 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 C11H22N2O4, Product Details of C11H22N2O4.

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

Sam, Joseph published the artcileHypotensive agents. Pyridinecarboxamides and piperidinecarboxamides, Related Products of amides-buliding-blocks, the publication is Journal of the American Chemical Society (1959), 710-13, database is CAplus.

Nicotinic acid (100 g.) in 2 l. CH₂Cl₂ treated gradually with 81 g. Et₃N, the mixture treated at 0-5° with 95 g. ClCO₂Et during 15-20 min., kept 0.5 hr. at 0°, treated with 57 g. pyrrolidine at 0-5°, warmed to room temperature, after 2 hrs. washed twice with 150 cc. H₂O, and distilled gave 90 g. 1-nicotinoylpyrrclidine, b_0.3 131-3°; methiodide m. 213.5-14.5° (MeCN), 87% yield. Similarly were prepared the following compounds (b.p./mm. and % yield given): N,N-diethylamide of isonicotinic acid (I), 109°/0.5 62; morpholide (II) of I, 142-5°/0.4, 55 [II.PhCH₂CH₂Br m. 214-15° (MeOH-Me₂CO), 97%]; morpholide (III) of nicotinic acid (IV), 190-5°/0.4, 48 [III.PhCH₂CH₂Br m. 212-13° (MeOH-Et₂O), 95%]; morpholide (V) of pyridine-2-carboxylic acid (VI), 142-3°/1, 59 [VI.MeI m. 175-6° (MeOH), 81%]; 2,6-dimethylmorpholide of IV, 138-40°/0.5, 57; 2,6-dimethylmorpholide (VII) of I, 135-7°/0.3, 50 [VII.PhCH₂CH₂Br m. 227-8° (MeOH-Et₂O), 94%]; 2,6-dimethylpiperidide of I, – (m. 73-4°), 20; 4-methylpiperazide of I, 133-5°/0.4, 39; p-ethoxyanilide (VIII) of IV, – (m. 170-5°), 50 [VIII.MeI m. 194-6°, 92%; VIII.PhCH₂CH₂Br m. 243-4° (MeOH), 88%]; p-dimethylaminoanilide (IX) of VI, -, 60 [IX.2HCl m. 227-30° (decomposition); IX.MeI m. 229-30° (decomposition)(MeOH), 98%]; p-dimethylaminoanilide (X) of IV, – (m. 185-7°), 25 [X.MeI m. 230-5° (decomposition)(MeOH), 95%]; p-dimethylaminoanilide (XI) of I, -, 38 [X.2HCl m. 175° (decomposition); X.MeI m. above 200° (decomposition)(MeOH), 90%]. The appropriate pyridinecarboxamide in MeOH or MeCN refluxed 24 hrs. with 10-20% suitable halide, the resulting quaternary salts in H₂O or EtOH hydrogenated over PtO₂ (0.3 g./0.1 mole) at 50-60 lb. during 15-30 hrs., filtered, basified strongly with 50% aqueous NaOH, extracted with Et₂O, and the extract worked up yielded the corresponding piperidinecarboxamide. N,N-Diethylnipecotamide (XII) (19 g.), 20 g. PhCH:CHCH₂Br, and 20 g. K₂CO₃ in 200 cc. PhMe refluxed 3 hrs. with stirring, cooled, washed with H₂O, dried, and distilled yielded 27 g. 1-cinnamyl derivative of XII, b_0.4 184-7°. Similarly were prepared the following 1-substituted piperidinecarboxamides (b.p./mm. and % yield given): 1-Ph(CH₂)₂ deriv, of XII, 173°/0.3, 86 (n²⁷_D 1.5221); 1-Ph₂CH derivative of XII.HBr, -, 20 [m. 234.5-35° (MeOH)]; 1-PhCH₂ derivative of the 4-isomer of XII, 173-5°/0.7, 87; 1-Me derivative of the pyrrolidide (XIII) of nipecotic acid (XIV), 111-14°/0.3, 89; 1-PhCH₂CH₂ derivative of XIII, 181-3°/0.1, 62 (n²⁵_D 1.5431); morpholide (XIV) of piperidine-2-carboxylic acid (XV), 143-5°/1.5, 65; 1-Me derivative of XIV, 121-3°/0.8, 87 (n³²_D 1.5013); 1-PhCH₂CH₂ derivative of XIV, 192-5°/0.4, 16 (n²⁴_D 1.5426); 1-Me derivative of the morpholide (XVI) of XIV, 118°/0.2, 72 (n^25.5_D 1.5065); 1-PhCH₂ derivative of XVI, 183-6°/0.3, 80; 1-PhCH₂CH₂ derivative of XVI, 188-92°/0.2, 85 (n³⁴_D 1.5406); 1-Ph(CH₂)₃ derivative of XVI, 203-6°/0.3, 71; 1-PhCH₂CH₂ derivative (XVII) of the morpholide of isonipecctic acid (XVIII), -, 85 [XVIII.HBr m. 279-80° (MeOH)]; 1-PhCH₂CH₂ derivative of the 2,6-dimethylmorpholide of XIV, 188-90°/0.2, 50 (n^24.5_D 1.5327); 1-PhCH₂CH₂ derivative (XIX) of the 2,6-dimethylmorpholide of XVIII, -, 78 [XIX.HBr m. 252-4° (H₂O)]; 1-Me derivative of the p-ethoxyanilide (XX) of XIV, -, 77 [m. 122-3° (aqueous MeOH)]: 1-PhCH₂CH₂ derivative (XXI) of XX, -, 82 [XXI.HBr m. 108-10° (decomposition) (Me₂CO)]; p-dimethylaminoanilide (XXII) of XV, -, 93 [m. 127-30° (aqueous MeOH)] [XXII.2HCl m. 248-50° (decomposition)(MeOH)]; p-dimethylaminoanilide (XXIII) of XVIII, [m. 197-8° (MeOH)], 90 [XXIII.2HCl m. 252-4° (decomposition) (MeOH)]. The appropriate 1-methylpiperidinecarboxamide reduced with LiAlH₄ yielded the corresponding alkylaminomethyl derivatives of 1-methylpiperidine (alkylamino group, b.p./mm., % yield, m.p., and % yield of dimethiodide given): 3-pyrrolidino, 59°/0.3, 93, 264-6° (decomposition), 94(at 25° in MeCN); 2-morpholino, 79-82°/0.4, 63, 255-6° (decomposition), 55 (refluxed 6 hrs. in MeCN); 3-morpholino, 87-8°/0.8 (n^25.5_D 1.5202), -, 281-2° (decomposition), – (refluxed 6 hrs. in MeOH). 1-Nicotinoylpyrrolidine in Et₂O reduced with LiAlH₄ yielded 44% 3-pyrrolidinomethylpyridine, b_0.2 75-7°, n^25.5_D 1.5202. XII (27.6 g.) and 18.2 g. styrene oxide heated 18 hrs. on the steam bath, the mixture dissolved in Et₂O and extracted with 6N HCl, the extract neutralized with NaOH and extracted with Et₂O, and the extract worked up gave 32.2 g. N,N-diethyl-1-(2-hydroxy-2-phenylethyl)nipecotamide, b_3.5 228-30°. XII (27.6 g.), 23.6 g. p-O₂NC₆H₄Cl, and 20.2 g. Et₃N heated 20 hrs. on the steam bath, cooled, triturated with H₂O, and filtered gave 45.1 g. N,N-diethyl-1-(p-nitrophenyl)nipecotamide (XXIV), m. 99.5-101.5° (EtOH). XXIV (15.3 g.) in 200 cc. EtOH hydrogenated at room temperature and 50 lb. over Raney Ni during 15 min., filtered, evaporated, the residue dissolved in Et₂O, and the solution saturated with dry Et₂O yielded 50% p-NH₂ analog di-HCl salt of XXIV, m. 227.5-8.5° (MeOH-EtOAc). 3-(3-Pyridyl)-acrylic acid (prepared in 79% yield from 3-pyridinecarboxaldehyde and malonic acid) treated in the usual manner with ClCO₂Et and morpholine in CH₂Cl₂ yielded 79% 4-[3-(3-pyridyl)acrylyl]morpholine (XXVI), m. 141-3° (MeCN). XXVI in MeOH hydrogenated at 60 lb. over 5% Pd-C yielded 87% 4-[3-(3-pyridyl)propionyl]morpholine (XXVII), b₁ 188-90°, n^24.5_D 1.5457. XXVII and excess PhCH₂CH₂Br in MeCN refluxed 18 hrs., the MeCN removed in vacuo, the residual oil dissolved in H₂O, the solution hydrogenated over PtO₂ at 60 lb. and 50°, and the mixture worked up in the usual manner yielded 84% 4-[3-(1-phenethyl-3-piperidyl)propionyl]morpholine, b_0.3 217-19°.

Journal of the American Chemical Society published new progress about 530-40-5. 530-40-5 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N,N-Diethylisonicotinamide, and the molecular formula is C10H14N2O, Related Products of amides-buliding-blocks.

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

Lv, Xue-Jiao published the artcileBronsted acid-catalyzed dynamic kinetic resolution of in situ formed acyclic N,O-hemiaminals: cascade synthesis of chiral cyclic N,O-aminals, Name: 2-Chloroacetamide, the publication is Organic Chemistry Frontiers (2021), 8(22), 6309-6316, database is CAplus.

A Bronsted acid-catalyzed cascade acyclic N,O-hemiaminal formation/oxa-Michael reaction is developed for the synthesis of cis-2,6-disubstituted tetrahydropyrans bearing an exo amide group, i.e., cyclic N,O-aminals. By using TsOH, various different amides including carboxyamides, carbamates, sulfonamides and even phosphoramides were applicable for the designed reaction sequence. By using chiral phosphoric acid, a wide range of enantioenriched cyclic N,O-aminal scaffolds were obtained. Detailed mechanistic investigations revealed that the good enantioselectivity can be attributed to a H₂O controlled dynamic kinetic resolution of the in situ formed acyclic N,O-hemiaminal intermediate during the reaction process. Furthermore, a number of divergent transformations of the obtained products were investigated, leading to various synthetically useful heterocyclic architectures.

Organic Chemistry Frontiers 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, Name: 2-Chloroacetamide.

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

Nodling, Alexander R. published the artcileCyanine dye mediated mitochondrial targeting enhances the anti-cancer activity of small-molecule cargoes, Related Products of amides-buliding-blocks, the publication is Chemical Communications (Cambridge, United Kingdom) (2020), 56(34), 4672-4675, database is CAplus and MEDLINE.

Organelle-specific delivery systems are of significant clin. interest. The authors demonstrate the use of common cyanine dyes Cy3 and Cy5 as vectors for targeting and delivering cargoes to mitochondria in cancer cells. Specifically, conjugation to the dyes can increase cytotoxicity by up to 1000-fold.

Chemical Communications (Cambridge, United Kingdom) 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, Related Products of amides-buliding-blocks.

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

Suzuki, Tateki published the artcileCrystal structures reveal an elusive functional domain of pyrrolysyl-tRNA synthetase, HPLC of Formula: 2418-95-3, the publication is Nature Chemical Biology (2017), 13(12), 1261-1266, database is CAplus and MEDLINE.

Pyrrolysyl-tRNA synthetase (PylRS) is a major tool in genetic code expansion using noncanonical amino acids, yet its structure and function are not completely understood. Here, we describe the crystal structure of the previously uncharacterized essential N-terminal domain of this unique enzyme from Methanosarcina mazei in complex with tRNA^Pyl. This structure explains why PylRS remains orthogonal in a broad range of organisms, from bacteria to humans. The structure also illustrates why tRNA^Pyl recognition by PylRS is anticodon-independent; the anticodon does not contact the enzyme. Then, using standard microbiol. culture equipment, we established a new method for laboratory evolution, PANCE, a noncontinuous counterpart of previously developed phage-assisted continuous evolution (PACE). With this method, we evolved novel PylRS variants with enhanced activity and amino acid specificity. Finally, we employed an evolved PylRS variant to determine its N-terminal domain structure and showed how its mutations improved PylRS activity in the genetic encoding of N^ε-(tert-butoxycarbonyl)-L-lysine (BocK), a noncanonical amino acid.

Nature Chemical Biology 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 C5H10N2OS, HPLC of Formula: 2418-95-3.

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

Mijin, Dusan Z. published the artcileSynthesis of substituted 3-cyano-2-pyridones. Part IV. Influence of 3-alkyl-2,4-pentanedione and N-alkylcyanoacetamide structure on the enzyme-catalyzed synthesis of substituted 3-cyano-2-pyridones, SDS of cas: 15029-36-4, the publication is Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry (2006), 45B(4), 993-1003, database is CAplus.

Lipase from Candida rugosa was used to study the influence of 3-alkyl-2,4-pentanedione and N-alkylcyanoacetamide structure on the enzyme-catalyzed reaction of pyridone ring formation in water at 40°. Starting with 1,3-diketones and cyanoacetamides and for comparison, the expected corresponding 3-cyano-2-pyridones were synthesized by chem. methods. Bulkier substituents lower the initial reaction rate of the enzyme-catalyzed reactions and consequently the yield of the corresponding pyridones. N-alkylcyanoacetamides are more reactive in comparison to the corresponding 3-alkyl-2,4-pentanediones with respect to the obtained yields of 3-cyano-2-pyridones.

Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry published new progress about 15029-36-4. 15029-36-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Aliphatic hydrocarbon chain,Amide, name is 2-Cyano-N-ethylacetamide, and the molecular formula is C5H8N2O, SDS of cas: 15029-36-4.

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

Surikova, O. V. published the artcileSynthesis, Antihelminthic and Insecticidal Activity of 2-[3-Methyl-6-Methoxy-7-(n-Propoxy)-3,4-Dihydroisoquinolin-1]Ethanoic Acid Amides, HPLC of Formula: 15029-36-4, the publication is Pharmaceutical Chemistry Journal (2017), 51(1), 22-25, database is CAplus.

Cyclocondensation of O-n-propylated eugenol with cyanoacetamides was used to synthesize 2-[3-methyl-6-methoxy-7-(n-propoxy)-3,4-dihydroisoquinolin-1]ethanoic acid amides. The hydrochlorides of these compounds were tested for antihelminthic and insecticidal activity. The most active compounds were amides containing a cyclic amine fragment (pyrrolidine, piperidine, morpholine), which had greater activity than Pyrantel. Compounds without substituents at the amide nitrogen and the N-ethylamide had insecticidal activity at the levels of diazinon and pirimiphos.

Pharmaceutical Chemistry Journal published new progress about 15029-36-4. 15029-36-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Aliphatic hydrocarbon chain,Amide, name is 2-Cyano-N-ethylacetamide, and the molecular formula is C20H18BrN3, HPLC of Formula: 15029-36-4.

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