Month: November 2022

Kiec-Kononowicz, K. published the artcileNew developments in A₁ and A₂ adenosine receptor antagonists, Application of N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, the publication is Pure and Applied Chemistry (2001), 73(9), 1411-1420, database is CAplus.

A review with references The aim of this article is to briefly present progress in the development of the potent adenosine receptor (AR) antagonists with high selectivity for either Al, A_2A or A_2B ARs. The structural requirements for each AR subtype were discussed as well as their potential therapeutic use. In the search for new AR antagonists. series of imidazo-, pyrimido-, and diazepino-purindione derivatives as well as oxazolo-, oxazino-, and oxazepino-purindiones were designed, synthesized, and preliminarily evaluated in pharmacol. studies. Oxygen-containing tricyclic derivatives were shown to be moderately potent AR antagonists exhibiting selectivity either for A₁ or A_2A ARs. Tricyclic purindiones with nitrogen in the third ring were generally more A₂A AR selective. The compounds tested in vivo according to the Antiepileptic Drug Development Program of the National Institutes of Health (USA) were generally active as anticonvulsants in chem. induced seizures.

Pure and Applied Chemistry published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Application of N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide.

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

Pernet, Erwan published the artcileLeukotriene B₄-type I interferon axis regulates macrophage-mediated disease tolerance to influenza infection, Quality Control of 321673-30-7, the publication is Nature Microbiology (2019), 4(8), 1389-1400, database is CAplus and MEDLINE.

Host defense against influenza A virus (IAV) infection depends not only on host resistance to eliminate the virus, but also disease tolerance to limit lung tissue damage and maintain pulmonary function. Fatal IAV infections are frequently the result of a maladaptive immune response that compromises disease tolerance rather than host resistance to infection. Here, we show that the leukotriene B₄ (LTB₄)-type I interferon (IFN) axis promotes a distinct mechanism of disease tolerance to pulmonary IAV infection. We demonstrate that mice genetically deficient in LTB₄ signalling (Blt1R^-/-) are more susceptible to IAV infection compared to control mice, despite similar pulmonary viral loads. The increased susceptibility of Blt1R^-/- mice is associated with an accumulation of inflammatory monocyte-derived macrophages (IMMs) causing increased lung immunopathol. We mechanistically define that LTB₄ signalling via the BLT1 receptor enhances the activation of the type I IFN-α/β receptor (IFNAR)/ and signal transducer and activator of transcription 1 (STAT1), which leads to IFN-α production by interstitial macrophages to suppresse in situ IMM proliferation. Importantly, the delivery of a single dose of LTB₄ at the peak viral load reduces IMM proliferation, controls tissue damage and increases survival without affecting host resistance to IAV.

Nature Microbiology 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, Quality Control of 321673-30-7.

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

Krivokolysko, D. S. published the artcileSynthesis, Structure, and Analgesic Activity of 4-(5-Cyano-{4-(fur-2-yl)-1,4-dihydropyridin-3-yl}carboxamido)benzoic Acids Ethyl Esters, Synthetic Route of 79-07-2, the publication is Russian Journal of General Chemistry (2021), 91(12), 2588-2605, database is CAplus.

A series of new hybrid mols. containing fragments of anesthesin and 4-(2-furyl)-1,4-dihydronicotinonitrile have been obtained starting from diketene, Et 4-aminobenzoate, cyanothioacetamide, and furfural. The obtained compounds have been investigated for the analgesic activity in vivo (rats) in the orofacial trigeminal pain and acetic acid induced writhing tests. The compounds exhibiting analgesic effect superior to that of the reference drug (metamizole sodium) have been revealed. Mol. docking has been performed for the considered compounds with respect to a wide range of protein targets, including cyclooxygenases COX-1 and COX-2.

Russian Journal of General 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, Synthetic Route of 79-07-2.

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

Zhang, Di published the artcileCatalytic hydrolysis: A novel role of zero-valent iron in haloacetonitrile degradation and transformation in unbuffered systems, HPLC of Formula: 79-07-2, the publication is Science of the Total Environment (2021), 149537, database is CAplus and MEDLINE.

Efforts to remove highly toxic haloacetonitriles (HANs) is an important step to reduce health risks associated with disinfection by product exposure. Zero valent iron (ZVI) is a versatile material, whose reductant, sorbent and coagulant role has been well understood. However, their catalytic role is less known. In this study, the degradation and transformation of HANs in ZVI system were investigated. Significant decreases of the four HANs in ZVI system were observed, and haloacetamides and haloacetic acids (hydrolysis products of HANs) were the dominant transformation products of HANs. However dehalogenated HANs, Fe (II) and Fe (III) were rarely detected after reaction, indicating that the ZVI acted as a catalyst to promote the hydrolysis of HANs, rather than other previously reported causes (dehalogenation or redox reaction). The HAN degradation rates were dramatically affected by the initial pH, ZVI doses and initial HAN concentration Kinetic anal. indicated that HAN removal was enhanced with the increase of initial pH (5-9), ZVI doses (1-10 g/L), and initial HAN concentration (25-200μg/L). ZVI induced the transformation of HANs to haloacetamides, haloacetic acids and other de-halogenated compounds, which reduced the cytotoxicity and genotoxicity by 88% and 85%, resp. This study helped to understand the fate of HAN during the transmission in cast iron pipes, and provided a theor. foundation for future HAN control and monitoring efforts.

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 C10H11NO4, HPLC of Formula: 79-07-2.

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

Horvath, Daniel Vajk published the artcileRegioexhaustive Functionalization of the Carbocyclic Core of Isoquinoline: Concise Synthesis of Oxoaporphine Core and Ellipticine, Formula: C11H16BNO3, the publication is Synthesis (2018), 50(11), 2181-2190, database is CAplus.

A general and versatile strategy has been developed for the functionalization of the carbocyclic core of the isoquinoline. This regioexhaustive approach employs electrophilic halogenation as a toolbox methodol. and delivers highly decorated intermediates that can be further elaborated toward medicinally relevant building blocks or natural products.

Synthesis published new progress about 146140-95-6. 146140-95-6 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (2-Pivalamidophenyl)boronic acid, and the molecular formula is C11H16BNO3, Formula: C11H16BNO3.

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

Codina, Pau published the artcileSacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension., SDS of cas: 137862-53-4, the publication is ESC heart failure (2022), 9(4), 2170-2180, database is MEDLINE.

AIMS: Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS-HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF-PH treated with sacubitril/valsartan. METHODS AND RESULTS: This single-arm, investigator-initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF-PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre-ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B-line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre-ARNI vs. ARNI ON, mPAP significantly declined by -4.99 mmHg [95% confidence interval (CI) -5.55 to -4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre-ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B-lines, and QoL. Mean loop diuretic management did not differ between periods. CONCLUSIONS: Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF-PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH.

ESC 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, SDS of cas: 137862-53-4.

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

Culbertson, Townley P. published the artcileNew 7-substituted quinolone antibacterial agents. The synthesis of 1-ethyl-1,4-dihydro-4-oxo-7-(2-thiazolyl and 4-thiazolyl)-3-quinolinecarboxylic acids, Related Products of amides-buliding-blocks, the publication is Journal of Heterocyclic Chemistry (1987), 24(6), 1509-20, database is CAplus.

A series of 1-ethyl-1,4-dihydro-4-oxo-7-(4-thiazolyl)-3-quinolinecarboxylic acids e.g. I (R = NH₂, MeNH, AcNCH₂, Me₂N, 3-pyridyl, morpholino, etc.; R¹,R² = H, F), and 1-ethyl-1,4-dihydro-4-oxo-7-(2-thiazolyl)-3-quinolinecarboxylic acids were prepared Also prepared was 10-[2-(aminomethyl)-4-thiazolyl]-9-fluoro-2,3-dihydro-3-methyl-7–oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (II). Analogs with basic amine substituents on the thiazole moiety were found to have antibacterial activity.

Journal of Heterocyclic 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, Related Products of amides-buliding-blocks.

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

Emre, Ceren published the artcileAge-related changes in brain phospholipids and bioactive lipids in the APP knock-in mouse model of Alzheimers disease, Application In Synthesis of 321673-30-7, the publication is Acta Neuropathologica Communications (2021), 9(1), 116, database is CAplus and MEDLINE.

Sustained brain chronic inflammation in Alzheimers disease (AD) includes glial cell activation, an increase in cytokines and chemokines, and lipid mediators (LMs), concomitant with decreased pro-homeostatic mediators. The inflammatory response at the onset of pathol. engages activation of pro-resolving, pro-homeostatic LMs followed by a gradual decrease. We used an APP knock-in (App KI) AD mouse that accumulates β-amyloid (Aβ) and presents cognitive deficits (at 2 and 6 mo of age, resp.) to investigate LMs, their precursors, biosynthetic enzymes and receptors, glial activation, and inflammatory proteins in the cerebral cortex and hippocampus at 2-, 4-, 8- and 18-mo-old in comparison with wild-type (WT) mice. We used LC-mass-spectrometry and MALDI mol. imaging to analyze LMs and phospholipids, and immunochem. for proteins. Our results revealed an age-specific lipid and cytokine profile, and glial activation in the App KI mice. Despite an early onset of Aβ pathol., pro-inflammatory and pro-resolving LMs were prominently increased only in the oldest age group. Furthermore, the LM biosynthetic enzymes increased, and their receptor expression decreased in the aged App KI mice. Arachidonic acid (AA)-containing phospholipid mol. species were elevated, correlating with decreased cPLA2 activity. MALDI mol. imaging depicted differential distribution of phospholipids according to genotype in hippocampal layers. Brain histol. disclosed increased microglia proliferation starting from young age in the App KI mice, while astrocyte numbers were enhanced in older ages. Our results demonstrate that the brain lipidome is modified preferentially during aging as compared to amyloid pathol. in the model studied here. However, alterations in phospholipids signal early pathol. changes in membrane composition

Acta Neuropathologica Communications 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, Application In Synthesis of 321673-30-7.

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

Hackett, Brent A. published the artcileSirtuin inhibitors are broadly antiviral against arboviruses, Related Products of amides-buliding-blocks, the publication is mBio (2019), 10(4), e01446-19/1-e01446-19/12, database is CAplus and MEDLINE.

Arthropod-borne viruses are diverse pathogens and are often associated with human disease. These viruses span multiple genera, including flaviviruses, alphaviruses, and bunyaviruses. In a high-throughput drug screen, we found that tenovin-1 was antiviral against the flaviviruses Zika virus and dengue virus. Tenovin-1 is a sirtuin inhibitor, and here we found that inhibition of sirtuins, but not inhibition of the related histone deacetylases, is potently antiviral against diverse arboviruses. Sirtuin inhibitors block infection of arboviruses in multiple human cell types. We found that sirtuin inhibitors arrest infection downstream of entry but that they do so at an early step, preventing the accumulation of viral RNA and protein. However, sirtuin inhibitors had no impact on the replication of flaviviral replicons, suggesting a defect in the establishment of replication. Consistent with this, we found that sirtuin inhibitors impacted double-stranded RNA (dsRNA) accumulation during flaviviral infection. Since these viruses infect vector insects, we also tested whether sirtuin inhibitors impacted infection of adult flies and found that these inhibitors blocked infection; therefore, they target highly conserved facets of replication. Taken together, these results suggest that sirtuin inhibitors represent a new class of potent host-targeting antivirals. IMPORTANCE Arthropod-borne viruses are diverse pathogens and are associated with human disease. Through high-throughput drug screening, we found that sirtuin inhibitors are potently antiviral against diverse arboviruses, including flaviviruses such as West Nile virus, bunyaviruses such as Rift Valley fever virus, and alphaviruses such as chikungunya virus. Sirtuin inhibitors block infection of these viruses in multiple human cell types. Moreover, we found that sirtuin inhibitors arrest infection downstream of entry but that they do so at an early step, preventing the accumulation of viral RNA and protein. Since these viruses infect vector insects, we also tested whether sirtuin inhibitors impacted infection of adult flies and found that these inhibitors blocked infection; therefore, they target highly conserved facets of replication. Taken together, these results suggest that sirtuin inhibitors represent a new class of potent host-targeting antivirals.

mBio 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, Related Products of amides-buliding-blocks.

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

Bowler, Frank R. published the artcileDNA Analysis by Dynamic Chemistry, HPLC of Formula: 186046-83-3, the publication is Angewandte Chemie, International Edition (2010), 49(10), 1809-1812, S1809/1-S1809/29, database is CAplus and MEDLINE.

Herein we report the application of dynamic chem. to DNA anal., offering the prospect of nonenzymic genotyping of genomic DNA amplified by polymerase chain reaction (PCR). This was achieved by the synthesis of a PNA strand that contained a blank position opposite the nucleobase under anal. in a complementary DNA template. A reversible reaction, between this PNA/DNA duplex (specifically the secondary amine of the “PNA blank”) and four aldehyde-modified nucleobases, means that the templating power of Watson-Crick base pairing and base stacking would be expected to drive the selection of the fully complementary iminium nucleobase. Subsequent reduction and MALDI-TOF mass spectrometry would allow rapid determination of base incorporation.

Angewandte Chemie, International Edition 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, HPLC of Formula: 186046-83-3.

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