Month: December 2022

Perrone-Filardi, Pasquale published the artcileRenin-angiotensin-aldosterone system inhibition in patients affected by heart failure: efficacy, mechanistic effects and practical use of sacubitril/valsartan. Position Paper of the Italian Society of Cardiology, COA of Formula: C24H29N5O3, the publication is European Journal of Internal Medicine (2022), 8-16, database is CAplus and MEDLINE.

A review. Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacol. treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the pos. effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clin. trials and observational studies investigated its role in different clin. settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients′ clin. profile is relevant to implement the use of ARNI in the clin. practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiol. on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community.

European Journal of Internal Medicine published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, COA of Formula: C24H29N5O3.

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

Nagl, Michael published the artcileThe BF₃.OEt₂-assisted conversion of nitriles into thioamides with Lawesson’s reagent, SDS of cas: 64559-06-4, the publication is Synthesis (2008), 4012-4018, database is CAplus.

A method for the thiolysis of nitriles by applying Lawesson’s reagent and facilitated by the addition of BF₃.OEt₂ is reported. The method opens an easy access to primary thioamides. Aromatic, benzylic, and aliphatic nitriles were converted into the corresponding thioamides in high to quant. yields (even in unfavorable cases, e.g., ortho-substituted benzonitriles). The reaction was performed in MeO(CH₂)₂OMe/THF or PhMe/OEt₂ solvent mixtures at 20-50°, and exhibited considerable selectivity in the case of multifunctional nitrile substrates, such as cyanomethyl N-acetylphenylalaninate, BzCH₂CN, 4-NCC₆H₄CONH₂, 4-AcC₆H₄CN, or 3-pentenenitrile.

Synthesis 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

Zaitseva, N.A. published the artcileSynthesis of fluorinated ketones with organolithium compounds and N,N-dialkylamides of fluorinated acids, Product Details of C6H10F3NO, the publication is Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1961), 831-5, database is CAplus.

cf. CA 53, 17933g. Adding 17.2 g. CHF₂CONEt₂ (I) in Et₂O to PhLi (0.1 mole PhBr) in Et₂O at -70° and stirring 2 hrs. gave after treatment with dilute HCl 83% CHF₂Bz, b_10-12 63-5°, n²⁰_D 1.4900. Similar reaction with crystalline PhLi in MePh gave a 67% yield, while the use of PhNa in MePh gave but 29% product. 2-Thienyllithium and I gave 75% 2-CHF₂-COC₄H₃S, b₁₁ 77-80°, b₁₃ 80°. Similarly, PhLi and CF₃CONEt₂ (II) gave 74% CF₃Bz, b³⁷ 66-8°, 1.4578, in Et₂O, while the yield was 54.5% in MePh. 2-Thienyllithium and II in Et₂O gave 39% 2-CF₃COC₄H₃S, b_23-4 67°. CF₃COCl and Et₂NH in Et₂O at 0° gave 47.4% II, b₄₃ 74-5°. PhLi in Et₂O and CHFClCONEt₂ gave 53% CHFClBz, b₁₁ 91°. Addition of 40.8 g. I to 0.36 mole BuLi in Et₂O over 2 hrs. at room temperature gave 32.6% CHF₂COBu, b. 111-12°.

Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya published new progress about 360-92-9. 360-92-9 belongs to amides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Amine,Aliphatic hydrocarbon chain,Amide, name is N,N-Diethyl-2,2,2-trifluoroacetamide, and the molecular formula is C4Br2N2O4S, Product Details of C6H10F3NO.

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

Simonov, A. Yu. published the artcileOptimization of the Synthesis of New Antibacterial Compounds with Tris(1-Alkylindol-3-yl)Methylium Fragments, Synthetic Route of 79-07-2, the publication is Pharmaceutical Chemistry Journal (2021), 54(12), 1263-1268, database is CAplus.

A new optimal synthetic scheme for new antibacterial compounds I (R = H, Me) combining tris-(1-alkyindol-3-yl)methylium and 3-(indol-1-yl)maleimide in their structures was developed. The proposed method provided a significant increase in the product yield, reduced the labor intensiveness and number of steps, and used readily accessible starting reagents. A good yield was achieved for 3-(formylindol-1-yl)-4-chloromaleimide, a universal precursor enabling two-step syntheses of target tri(indolyl)methanes II (R¹ = H, NH₂, NMe₂) and production of an extensive library of analogous potentially active compounds from other 1-alkylindoles and various amines and thiols.

Pharmaceutical Chemistry Journal 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 C13H21BN2O2, Synthetic Route of 79-07-2.

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

Rao, Ashwin U. published the artcileSynthesis and structure-activity relationships of 2-(1,4′-bipiperidin-1′-yl)thiazolopyridines as H₃ receptor antagonists, HPLC of Formula: 947533-21-3, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(21), 6176-6180, database is CAplus and MEDLINE.

A series of 2-(1,4′-bipiperidin-1′-yl)thiazolopyridines I (X = N, Y = CH; X = CH, Y = N; R = H, H₂N, CN, Cl, MeCONH, 4-NCC₆H₄, 2-fluoro-3-pyridyl, 5-pyrimidyl, etc.) was synthesized and evaluated as a new lead of non-imidazole histamine H₃ receptor antagonists. Introduction of diversity at the 6-position of the pyridine ring was designed to enhance in vitro potency and decrease hERG activity. The structure-activity relationships for these new thiazolopyridine antagonists are discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about 947533-21-3. 947533-21-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Boronic acid and ester,Amine,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (6-Acetamidopyridin-3-yl)boronic acid, and the molecular formula is C7H9BN2O3, HPLC of Formula: 947533-21-3.

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

Shaik, Jeelan Basha published the artcileSynthesis, Biological Evaluation, and Molecular Docking of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene Analogs: New Dual AChE Inhibitors as Potential Drugs for the Treatment of Alzheimer’s Disease, Name: 2-Cyano-N-ethylacetamide, the publication is Chemical Biology & Drug Design (2016), 88(1), 43-53, database is CAplus and MEDLINE.

Alzheimer’s disease onset and progression are associated with the dysregulation of multiple and complex physiol. processes, and a successful therapeutic approach should therefore address more than one target. In line with this modern paradigm, a series of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene analogs (4a-q) were synthesized and evaluated for their multitarget-directed activity on acetylcholinesterase, butyrylcholinesterase (BuChE), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, and amyloid-β peptide (Aβ) specific targets for Alzheimer’s disease therapy. Most of the synthesized compounds showed remarkable acetylcholinesterase inhibitory activities in low nM concentrations and good ABTS radical scavenging activity, however, no evidence of BuChE inhibitory activity. Among them, 3-bromobenzylamide derivative N-(3-bromobenzyl)-8-imino-2-oxo-2H,8H-pyrano [2,3-f]chromene-9-carboxamide (4m) exhibited the best acetylcholinesterase inhibitory activity with IC₅₀ value of 13±1.4 nM which is 51-fold superior to galantamine, a reference drug. Kinetic and mol. docking studies indicated (4m) as mixed-type inhibitor, binding simultaneously to catalytic active and peripheral anionic sites of acetylcholinesterase. Five compounds N-cyclohexyl-8-imino-2-oxo-2H,8H-pyrano[2,3-f] chromene-9-carboxamide (4e), 8-imino-9-(morpholine-4-carbonyl)-2H,8H-pyrano [2,3-f]chromen-2-one (4f), N-benzyl-8-imino-2-oxo-2H,8H-pyrano[2,3-f] chromene-9-carboxamide (4g), 8-imino-N-(1-(4-methoxyphenyl)ethyl)-2-oxo-2H,8H- pyrano[2,3-f]chromene-9-carboxamide (4j), and N-(2,4-dimethoxybenzyl)-8-imino-2-oxo-2H,8H- pyrano[2,3-f]chromene-9-carboxamide (4k) have shown 1.4- to 2.5-fold of higher antioxidant activities than trolox. Interestingly, the most active compound (4m) demonstrated dosage-dependent acceleration of Aβ_1-42 aggregation, which may reduce toxicity of oligomers. Overall, these results lead to discovery of fused tricyclic coumarins as promising dual binding site inhibitors of acetylcholinesterase and afford multifunctional compounds with potential impact for further pharmacol. development in Alzheimer’s therapy.

Chemical Biology & Drug Design 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 C12H10O4S, Name: 2-Cyano-N-ethylacetamide.

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

Shaik, Jeelan Basha published the artcileSynthesis, pharmacological assessment, molecular modeling and in silico studies of fused tricyclic coumarin derivatives as a new family of multifunctional anti-Alzheimer agents, Quality Control of 15029-36-4, the publication is European Journal of Medicinal Chemistry (2016), 219-232, database is CAplus and MEDLINE.

A series of fused tricyclic coumarin derivatives bearing iminopyran ring connected to various amido moieties was developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. In vitro studies revealed that most of these compounds exhibited high inhibitory activity on acetylcholinesterase (AChE), with IC₅₀ values ranging from 0.003 to 0.357 μM which is 2-220 folds more potent than the pos. control, galantamine. Their inhibition selectivity against AChE over butyrylcholinesterase (BuChE) has increased about 194 fold compared with galantamine. The developed compounds also showed potent ABTS radical scavenging activity (IC₅₀ 7.98-15.99 μM). Specifically, the most potent AChE inhibitor, I (NR¹R² = NHCH₂C₆H₄Br-3) (II), (IC₅₀ 0.003 ± 0.0007 μM) has an excellent antioxidant profile as determined by the ABTS method (IC₅₀ 7.98 ± 0.77 μM). Moreover, cell viability studies in SK N SH cells showed that the compounds I (NR¹R² = NHCH₂C₆H₄Br-2, NHCH₂C₆H₄Br-3, NHCH₂C₆H₄Cl-2, NHCH₂C₆H₄Cl-3, NHCH₂C₆H₄CMe₃-4) (III) have significant neuroprotective effects against H₂O₂-induced cell death, and are not neurotoxic at all concentrations except I (NR¹R² = NHCH₂C₆H₄CMe₃-4) and II. The kinetic anal. of compound II proved that it is a mixed-type inhibitor for EeAChE (K_i1 0.0103 μM and K_i2 0.0193 μM). Accordingly, the mol. modeling study demonstrated that III with a substituted benzyl amido moiety possessed an optimal docking pose with interactions at catalytic active site (CAS) and peripheral anionic site (PAS) of AChE simultaneously and thereby they might prevent aggregation of Aβ induced by AChE. Furthermore, in silico ADMET prediction studies indicated that these compounds satisfied all the characteristics of CNS acting drugs. Most active inhibitor II is permeable to BBB as determined in the in vivo brain AChE activity. To sum up, the multipotent therapeutic profile of these novel tricyclic coumarins makes them promising leads for developing anti-Alzheimer agents.

European Journal of 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 C4H6O3, Quality Control of 15029-36-4.

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

Grbesa, Ivana published the artcileExpression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients, Computed Properties of 380315-80-0, the publication is PLoS One (2015), 10(4), e0124670/1-e0124670/17, database is CAplus and MEDLINE.

Background: Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD+-dependent protein deacetylases involved in the regulation of key cancer-associated genes. In this study we evaluated the relevance of these deacetylases in lung cancer biol. Material and Methods: Protein levels of SIRT1 and SIRT2 were determined in non-small cell lung cancer (NSCLC) cell lines and primary tumors from 105 patients. Changes in proliferation were assessed after SIRT1 and SIRT2 downregulation in lung cancer cell lines using siRNA-mediated technol. or tenovin-1, a SIRT1 and SIRT2 inhibitor. Results: High SIRT1 and SIRT2 protein levels were found in NSCLC cell lines compared with non-tumor lung epithelial cells. The expression of SIRT1 and SIRT2 proteins was also significantly higher in lung primary tumors than in normal tissue (P<0.001 for both sirtuins). Stronger nuclear SIRT1 staining was observed in adenocarcinomas than in squamous cell carcinomas (P = 0.033). Interestingly, in NSCLC patients, high SIRT1 and SIRT2 expression levels were associated with shorter recurrence-free survival (P = 0.04 and P = 0.007, resp.). Moreover, the combination of high SIRT1 and SIRT2 expression was an independent prognostic factor for shorter recurrence-free survival (P = 0.002) and overall survival (P = 0.022). In vitro studies showed that SIRT1 and/or SIRT2 downregulation significantly decreased proliferation of NSCLC. Conclusions: Our results support the hypothesis that SIRT1 and SIRT2 have a protumorigenic role in lung cancer, promoting cell proliferation. Moreover, the expression of these proteins is associated with poor prognosis in NSCLC patients and may help to identify those NSCLC patients with high risk of recurrence that could benefit from adjuvant therapy after resection.

PLoS One published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, Computed Properties of 380315-80-0.

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

Guo, Chuangxing published the artcileDesign of oxobenzimidazoles and oxindoles as novel androgen receptor antagonists, Formula: C8H9BFNO3, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(7), 2572-2578, database is CAplus and MEDLINE.

Oxobenzimidazoles (e.g., 1), a novel series of androgen receptor (AR) antagonists, were discovered through de novo design guided by structure-based drug design. The compounds in this series were reasonably permeable and metabolically stable, but suffered from poor solubility The incorporation of three dimensional structural features led to improved solubility In addition, the observation of a ‘flipped’ binding mode of an oxobenzimidazole analog in an AR ligand binding domain (LBD) model, led to the design and discovery of the novel oxindole series (e.g., 2, I) that is a potent full antagonist of AR.

Bioorganic & Medicinal Chemistry Letters published new progress about 849833-86-9. 849833-86-9 belongs to amides-buliding-blocks, auxiliary class Fluoride,Boronic acid and ester,Amine,Benzene,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester, name is (3-Fluoro-4-(methylcarbamoyl)phenyl)boronic acid, and the molecular formula is C8H9BFNO3, Formula: C8H9BFNO3.

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

Zhang, Juntian published the artcileAtypical Mode of [3 + 2]-Cycloaddition: Pseudo-1,3-dipole Behavior in Reactions of Electron-Deficient Thioamides with Benzynes, Quality Control of 360-92-9, the publication is Organic Letters (2018), 20(18), 5550-5553, database is CAplus and MEDLINE.

Thioamides bearing electron-withdrawing groups on the thiocarbonyl carbon atom react with benzynes [generated by the hexadehydro-Diels-Alder cycloisomerization] in an unprecedented fashion. Namely, the dihydrobenzothiazole products are consistent with a pathway involving initial formation of a stabilized ammonium ylide by a rare type of [3 + 2]-cycloaddition reaction. The fate of this species depends upon the nature of the substituents attached to the ylide nitrogen atom. The demonstration of new modes of reactivity represents the major advance arising from this study.

Organic Letters published new progress about 360-92-9. 360-92-9 belongs to amides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Amine,Aliphatic hydrocarbon chain,Amide, name is N,N-Diethyl-2,2,2-trifluoroacetamide, and the molecular formula is C8H7NO4, Quality Control of 360-92-9.

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