Month: November 2022

Tucker, J. A. published the artcileStructure-activity relationships of acyloxyamidine cytomegalovirus DNA polymerase inhibitors, Synthetic Route of 2447-79-2, the publication is Bioorganic & Medicinal Chemistry (2000), 8(3), 601-615, database is CAplus and MEDLINE.

This paper describes the structure-activity relationships of a new class of cytomegalovirus DNA polymerase inhibitors having two aryl groups joined by an acyloxyamidine linker. Examination of a series of analogs in which the terminal groups are varied revealed a very narrow SAR around the 2,4-dichlorophenyl group of the lead compound, but a variety of replacements for the benzothiazole ring are compatible with activity. The most notable of these is the compound with isoxazole ring, which provides a 30-fold enhancement in potency compared to the lead compound We also describe the design, synthesis and evaluation of 10 analogs in which the acyloxyamidine linker is modified or replaced by an isosteric group. Structure-activity relationship studies identified the linker -NH₂group as a critical pharmacophoric element. Ab initio MO calculations combined with qual. estimates of steric interaction energies suggest that the lowest energy conformations of the acyloxyamidine linker are characterized by an extended planar C_Ar-C=N-O-C arrangement and either a syn-periplanar or anti-periplanar N-O-C-C_Ar’ arrangement. Only the anti-periplanar conformation was observed in the crystal structures of three acyloxyamidines. The most active of the linker-modified compounds designed on the basis of these studies is the amidine carbamate compound, which is approx. one-third as potent in the cytomegalovirus DNA polymerase inhibition assay as the comparator acyloxyamidine. The activity of the amidine carbamate compound suggests that acyloxyamidines may bind to the cytomegalovirus DNA polymerase via an anti-periplanar conformation.

Bioorganic & Medicinal Chemistry published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C4Br2N2O4S, Synthetic Route of 2447-79-2.

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

Goldberg, Kristin published the artcileA facile synthesis of 3-trifluoromethyl-1,2,4-oxadiazoles from cyanamides, HPLC of Formula: 2451-91-4, the publication is Tetrahedron Letters (2014), 55(32), 4433-4436, database is CAplus.

A safe and facile method for the formation of 3-trifluoromethyl-5-amino-1,2,4-oxadiazoles, via a reversed addition of hydroxylamine to cyanamides, is reported. This two-pot procedure is suitable to scale-up and avoids the hazards associated with trifluoromethyl amidoxime synthesis.

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 C15H14N2, HPLC of Formula: 2451-91-4.

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

Zeymer, Uwe published the artcileUtilization of sacubitril/valsartan in patients with heart failure with reduced ejection fraction: real-world data from the ARIADNE registry., Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is European heart journal. Quality of care & clinical outcomes (2022), 8(4), 469-477, database is MEDLINE.

AIMS: To compare baseline characteristics of patients with heart failure with reduced ejection fraction (HFrEF) initiated on sacubitril/valsartan compared with patients continued on conventional heart failure (HF)-treatment in a European out-patient setting. METHODS AND RESULTS: Between July 2016 and July 2019, ARIADNE enrolled 8787 outpatients aged ≥18 years with HFrEF from 17 European countries. Choice of therapy was solely at the investigators’ discretion. In total, 4173 patients were on conventional HF-treatment (non-S/V group), while 4614 patients were on sacubitril/valsartan either at enrolment or started sacubitril/valsartan within 1 month of enrolment (S/V group). Of these, 2108 patients started sacubitril/valsartan treatment ±1 month around enrolment [restricted S/V (rS/V) group]. The average age of the patients was 68 years. Patients on S/V were more likely to have New York Heart Association (NYHA) class III or IV symptoms (50.3%, 44.6%, 32.1% in rS/V, S/V, and non-S/V, respectively) and had lower left ventricular ejection fraction (LVEF; 32.3%, 32.7%, and 35.4% in rS/V, S/V, and non-S/V, respectively; P < 0.0001). The most frequently received HF treatments were angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB; ∼84% in non-S/V), followed by β-blockers (∼80%) and mineralocorticoid receptor antagonists (MRAs; 53%). The use of triple HF therapy (ACEI/ARB/angiotensin receptor neprilysin inhibitor with β-blockers and MRA) was higher in the S/V groups than non-S/V group (48.2%, 48.2%, and 40.2% in rS/V, S/V, and non-S/V, respectively). CONCLUSION: In this large multinational HFrEF registry, patients receiving sacubitril/valsartan tended to be younger with lower LVEF and higher NYHA class. Fewer than half of the patients received triple HF therapy.

European heart journal. Quality of care & clinical outcomes 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 C19H14N2, Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid.

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

Myhre, Peder L. published the artcileChanges in cardiac biomarkers in association with alterations in cardiac structure and function, and health status in heart failure with reduced ejection fraction: the EVALUATE-HF trial, COA of Formula: C24H29N5O3, the publication is European Journal of Heart Failure (2022), 24(7), 1200-1208, database is CAplus and MEDLINE.

Aims : N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in heart failure with reduced ejection fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status. Methods and results : Patients in the EVALUATE-HF trial (n = 464) were randomized to sacubitril/valsartan or enalapril for 12 wk, followed by 12-wk open-label sacubitril/valsartan. Cardiac biomarkers, echocardiog., and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 wk. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67 ± 9 years, 75% male and 75% white). After 24 wk of treatment, NT-proBNP, sST2 and cTnT decreased by median (Q1, Q3) -31% (-55%, +6%), -6% (-19%, +8%) and – 3% (-13%, +8%), resp. (all p < 0.001). Decreases in NT-proBNP were associated with reductions in cardiac volumes and improvements in systolic and diastolic function and health status. Decreases in cTnT were associated with reductions in left ventricular mass, but not with changes in left ventricular function or KCCQ. Decreases in sST2 were consistently associated with improvements in health status, but not with measures of cardiac structure or function. There was no effect modification from treatment on the associations investigated (p for interaction >0.05) Conclusion : In HFrEF, serial changes in NT-proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in left ventricular mass and sST2 with changes in health status. These data highlight possible complementary pathophysiol. implications of changes in NT-proBNP, cTnT and sST2. Clin. Trial Registration: Identifier: NCT02874794.

European Journal of Heart Failure 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

Wijkman, Magnus O. published the artcileEffects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials, Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Cardiovascular Diabetology (2022), 21(1), 110, database is CAplus and MEDLINE.

Abstract: Background: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes. Methods: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF. Results: Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 wk: – 0.24%, 95% CI – 0.33 to – 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62-1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05-2.56, P = 0.030). In a pooled anal. of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (P_interaction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63-0.89, P = 0.001), compared with enalapril or valsartan. Conclusions: Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711

Cardiovascular Diabetology 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 C15H24O2, Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid.

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

Song, Liangliang published the artcilePyridine-Enabled C-N Bond Activation for the Rapid Construction of Amides and 4-Pyridylglyoxamides by Cooperative Palladium/Copper Catalysis, Safety of Isonicotinamide, the publication is Journal of Organic Chemistry (2020), 85(12), 8045-8054, database is CAplus and MEDLINE.

A pyridine-enabled C-N bond activation of peptidomimetics employing cooperative palladium/copper catalysis in water is developed. Diverse amides and 4-pyridylglyoxamides are simultaneously synthesized through two steps from com. available materials in a rapid, environmentally friendly, and high atom-economical manner.

Journal of Organic Chemistry published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C19H34ClN, Safety of Isonicotinamide.

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

Sledzinski, B. published the artcileStudies on the reaction of dialkyl phosphites with α-chloroacetophenones in the presence of ammonia, COA of Formula: C7H5Cl2NO, the publication is Organika (1979), 1-8, database is CAplus.

An extensive study showed that only RR¹CHCOC₆H₃Cl₂-2,4 (I; R = Br or Cl, R¹ = H, or R = R¹ = Cl) reacted with dialkyl phosphites in the presence of NH₃ to give the corresponding enol phosphates, whose importance as pesticides is steadily increasing. Under the same reaction conditions, I (R = R¹ = Br) yielded a complex mixture of at least 5 products, of which only I (R = Br, R¹ = H) and 2,4-Cl₂C₆H₃CONH₂ were identified. R₃CCOC₆H₃Cl₂-2,4 (R = Br or Cl) produced the corresponding benzamide and haloforms.

Organika published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C13H10O2, COA of Formula: C7H5Cl2NO.

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

Iqbal, Saqib A. published the artcileAcyl-Directed ortho-Borylation of Anilines and C7 Borylation of Indoles using just BBr₃, Recommanded Product: N-(4-Methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pivalamide, the publication is Angewandte Chemie, International Edition (2019), 58(43), 15381-15385, database is CAplus and MEDLINE.

Indoles are privileged heterocycles found in many biol. active pharmaceuticals and natural products. However, the selective functionalization of the benzenoid moiety in indoles in preference to the more reactive pyrrolic unit is a significant challenge. Herein we report that N-acyl directing groups enable the C7-selective C-H borylation of indoles using just BBr₃. This transformation shows some functional-group tolerance and notably proceeds with C6 substituted indoles. The directing group can be readily removed in situ and the products isolated as the pinacol boronate esters. Acyl-directed electrophilic borylation can be extended to carbazoles and anilines with excellent ortho selectivity. 4-Amino-indoles are amenable to this process, with acyl group installation and directed electrophilic C-H borylation enabling selective formation of C5-BPin-indoles.

Angewandte Chemie, International Edition published new progress about 2246585-66-8. 2246585-66-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester, name is N-(4-Methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pivalamide, and the molecular formula is C18H28BNO3, Recommanded Product: N-(4-Methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pivalamide.

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

Bedalov, A. published the artcileBiology, chemistry, and pharmacology of Sirtuins, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Methods in Enzymology (2016), 183-211, database is CAplus and MEDLINE.

A review. Sirtuins are a family of protein deacylases related by amino acid sequence and cellular function to the yeast Saccharomyces cerevisiae protein Sir2 (Silent Information Regulator-2), the first of this class of enzymes to be identified and studied in detail. Based on its initially discovered activity, Sir2 was classified as a histone deacetylase that removes acetyl groups from histones H3 and H4. The acetylation/deacetylation of these particular substrates leads to changes in transcriptional silencing at specific loci in the yeast genome, hence its name. Sirtuins, however, have been shown to regulate a wide variety of cellular processes beyond transcriptional repression in varied subcellular compartments and in different cell types. Mechanistically distinct from Zn²⁺-dependent deacylases, sirtuins use NAD as a cofactor in the removal of acetyl and other acyl groups linking metabolic status and posttranslational modification. Sirtuins’ unique position has made them attractive targets for small-mol. drug development. In this chapter, we describe the biol. roles, therapeutic areas in which sirtuins may play a role and development of small-mol. inhibitors of sirtuins employing phenotypic screening technologies ranging from assays in yeast, as well as biochem. screens to yield lead drug development candidates targeting a broad spectrum of human diseases.

Methods in Enzymology 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

Poudel, Yam B. published the artcileChemical Modification of Linkers Provides Stable Linker-Payloads for the Generation of Antibody-Drug Conjugates, Safety of (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, the publication is ACS Medicinal Chemistry Letters (2020), 11(11), 2190-2194, database is CAplus and MEDLINE.

Stability of antibody-drug conjugates (ADCs) in mouse serum is one of the critical requirements for the evaluation of ADCs in mouse tumor models. Described herein is a strategy to address the mouse serum instability of uncialamycin linker-payloads through various chem. approaches that involve modification of different parts of the linker and payload. This effort ultimately led to the identification of a m-amide p-aminobenzyl carbamate (MA-PABC) group that resulted in linkers with dramatic improvement of mouse serum stability without affecting the desired proteolytic cleavage.

ACS Medicinal Chemistry Letters 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, Safety of (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid.

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