Month: December 2022

Funnell, Richard A. published the artcileThree reactions leading to isomeric 2-(N,N-disubstituted amino)thiazol-5-yl ketones, Recommanded Product: Morpholine-4-carbothioamide, the publication is Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1987), 2311-15, database is CAplus.

N-Imidoyl-N,N-disubstituted thioureas PhNHCR:NCSR¹ (R = CMe₃, Ph, 4-MeOC₆H₄, 4-ClC₆H₄, 2-thienyl, R¹ = NMe₂, NPhMe, pyrrolidino, piperidino, morpholino, hexahydroazepino) react with α-halo ketones R²COCH₂R³ (I, R² = Me, R³ = Cl; R² = Me, CMe₃, Ph, 4-ClC₆H₄, 4-MeOC₆H₄, 4-O₂NC₆H₄, Me₂CH, R³ = Br) in the presence of Et₃N to give the expected 2-(N,N-disubstituted amino)thiazol-5-yl ketones II in high yield. The corresponding reactions of N-acyl-N,N-disubstituted thioureas RCONHCSR¹ with I lead to mixtures of II and III, which arise from rearrangement between cyclic intermediates. Mixtures of II and III are also formed by treating N,N-disubstituted thioureas R¹CSNH₂ with 2-bromo-1,3-diketones RCOCHBrCOR². The mixtures from the second and third routes contain the same products but in significantly different proportions. A mechanistic scheme which accounts for the main findings was developed. Characteristic mass spectral fragmentation patterns were particularly useful in identifying the substituents at positions 4 and 5 of the thiazole ring.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) 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, Recommanded Product: Morpholine-4-carbothioamide.

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

Birdsall, Robert E. published the artcileA sensitive multidimensional method for the detection, characterization, and quantification of trace free drug species in antibody-drug conjugate samples using mass spectral detection, Recommanded Product: (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, the publication is mAbs (2016), 8(2), 306-317, database is CAplus and MEDLINE.

Conjugation processes and stability studies associated with the production and shelf life of antibody-drug conjugates (ADCs) can result in free (non-conjugated) drug species. These free drug species can increase the risk to patients and reduce the efficacy of the ADC. Despite stringent purification steps, trace levels of free drug species may be present in formulated ADCs, reducing the therapeutic window. The reduction of sample preparation steps through the incorporation of multidimensional techniques has afforded analysts more efficient methods to assess trace drug species. Multidimensional methods coupling size-exclusion and reversed phase liquid chromatog. with ultra-violet detection (SEC-RPLC/UV) have been reported, but offer limited sensitivity and can limit method optimization. The current study addresses these challenges with a multidimensional method that is specific, sensitive, and enables method control in both dimensions via coupling of an online solid phase extraction column to RPLC with mass spectral detection (SPE-RPLC/MS). The proposed method was evaluated using an antibody-fluorophore conjugate (AFC) as an ADC surrogate to brentuximab vedotin and its associated parent maleimide-val-cit-DSEA payload and the derived N-acetylcysteine adduct formed during the conjugation process. Assay sensitivity was found to be 2 orders more sensitive using MS detection in comparison to UV-based detection with a nominal limit of quantitation of 0.30 ng/mL (1.5 pg on-column). Free-drug species were present in an unadulterated ADC surrogate sample at concentrations below 7 ng/mL, levels not detectable by UV alone. The proposed SPE-RPLC/MS method provides a high degree of specificity and sensitivity in the assessment of trace free drug species and offers improved control over each dimension, enabling straightforward integration into existing or novel workflows.

mAbs 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, Recommanded Product: (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

Pirrie, Lisa published the artcileDiscovery and validation of SIRT2 inhibitors based on tenovin-6: use of a ¹H-NMR method to assess deacetylase activity, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Molecules (2012), 12206-12224, database is CAplus and MEDLINE.

The search for potent and selective sirtuin inhibitors continues as chem. tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a ¹H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift anal. of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented.

Molecules 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

Rahimi, Marwa N. published the artcileProtein-protein inhibitor designed de novo to target the MEEVD region on the C-terminus of Hsp90 and block co-chaperone activity, Application In Synthesis of 2418-95-3, the publication is Chemical Communications (Cambridge, United Kingdom) (2019), 55(6), 846-849, database is CAplus and MEDLINE.

Protein-protein interactions control all cellular functions. Presented is the 1st de novo designed protein-protein interaction inhibitor that targets the C-terminus of heat shock protein 90 (Hsp90) and blocks co-chaperones from binding. Compound LB76, which was created from an Hsp90 co-chaperone, selectively pulls down Hsp90 from cell lysates, binds to Hsp90’s C-terminal domain, and blocks the interactions between Hsp90 and TPR-containing co-chaperones. Through these interactions, LB76 inhibits the protein-folding function of Hsp90. Blocking these protein-protein interactions between Hsp90 and C-terminal co-chaperones regulate the cell’s entire protein-folding machinery.

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, Application In Synthesis of 2418-95-3.

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

Krajsovszky, Gabor published the artcileNew synthetic approach to pyridazino[4,5-b]indoles by Pd(0)-catalyzed cross-coupling reaction, HPLC of Formula: 146140-95-6, the publication is Heterocycles (2001), 55(6), 1105-1111, database is CAplus.

5-Iodo-2-methylpyridazin-3(2H)-one readily underwent Suzuki coupling with protected anilinoboronic acids I (X = H, Cl) to yield the corresponding arylpyridazinones which proved to be suitable starting compounds to a ring closure – a 4 step pathway – to pyridazino[4,5-b]indoles II.

Heterocycles 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, HPLC of Formula: 146140-95-6.

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

Hirakata, Toshiaki published the artcileLeukotriene B₄ receptors as therapeutic targets for ophthalmic diseases, Safety of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Biochimica et Biophysica Acta, Molecular and Cell Biology of Lipids (2020), 1865(9), 158756, database is CAplus and MEDLINE.

A review. Leukotriene B₄ (LTB₄) is an inflammatory lipid mediator produced from arachidonic acid by multiple reactions catalyzed by two enzymes 5-lipoxygenase (5-LOX) and LTA₄ hydrolase (LTA₄H). The two receptors for LTB₄ have been identified: a high-affinity receptor, BLT1, and a low-affinity receptor, BLT2. Our group identified 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) as a high-affinity BLT2 ligand. Numerous studies have revealed critical roles for LTB₄ and its receptors in various systemic diseases. Recently, we also reported the roles of LTB₄, BLT1 and BLT2 in the murine ophthalmic disease models of mice including cornea wound, allergic conjunctivitis, and age-related macular degeneration. Moreover, other groups revealed the evidence of the ocular function of LTB₄. In the present review, we introduce the roles of LTB₄ and its receptors both in ophthalmic diseases and systemic inflammatory diseases. LTB₄ and its receptors are putative novel therapeutic targets for systemic and ophthalmic diseases.

Biochimica et Biophysica Acta, Molecular and Cell Biology of Lipids 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

El-Hanboushy, Sara published the artcileEco-friendly spectrophotometric evaluation of triple-combination therapies in the treatment strategy of patients suffering from hypertension during coronavirus pandemic – Spectral print recognition study, Computed Properties of 137862-53-4, the publication is Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (2022), 121523, database is CAplus and MEDLINE.

Recent studies have reported that using certain antihypertensive therapies such as angiotensin II receptor blockers (ARBs) and calcium channel blocker (CCBs) is associated with reduction of fatal outcomes and improving clin. characteristics of patients suffering from hypertension during coronavirus pandemic. Thus, in the current work an effective, innovative and eco-friendly spectrophotometric manner namely, parent spectrum extraction (PSE) was established for evaluation of recommended triple antihypertensive combination therapies incorporate valsartan (VAL) as ARBs, amlodipine besylate as CCBs (AML) and hydrochlorothiazide (HCT) as diuretic into single-pill in challengeable ratio. PSE manner composed of two complementary steps, auxiliary resolution coupled with data anal. resolution (DAR) and it is characterized by resolving the spectral bands of the drugs and extraction of their discrete parent spectra (D⁰); accordingly, enabling determination of each analyte at its λ_max. Auxiliary resolution of AML in triple mixture was applied to decrease complexity of overlapped spectra via constant multiplication (CM) followed by spectrum subtraction (SS) to obtain resolved mixture of VAL and HCT while data anal. resolution (DAR) of this binary mixture was applied via one of three novel methods namely, absorbance extraction (AE), peak-amplitude extraction (PE) and ratio extraction (RE) along with SS method. The proposed methods had analyzed VAL, AML and HCT in the range of 4.0-44.0 μg/mL, 4.0-40.0 μg/mL and 2.0-24.0 μg/mL, resp. with an excellent correlation coefficient (r ≥ 0.9999). Further, the proposed methods in PSR manner were validated as stated by ICH guidelines and it was found that accuracy and precision results are within the acceptable limit. The suggested procedures were effectively utilized for the concurrent quantification of VAL, AML and HCT in synthetic mixtures and tablets. The greenness of the proposed spectrophotometric methods was evaluated by National Environmental Methods Index (NEMI), the Anal. Eco-Scale, the Green Anal. Procedure Index (GAPI) and Anal. greenness metric (AGREE) where the four tools affirmed the eco-friendly nature of the proposed methods. A comparison between the outcomes of the studied methods with the official and reported ones was performed and no statistical difference was arisen between the methods regarding to accuracy and precision. The achieved results along with the simplicity, affordability and low-cost of the proposed methods recommended their appropriateness for the regular quality control examination and anal. of pure materials and pharmaceutical formulations as well as their applicability for the spectralprint recognition of the studied drugs.

Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy 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, Computed Properties of 137862-53-4.

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

Marx, Christian published the artcileThe sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing’s sarcoma cell line, HPLC of Formula: 380315-80-0, the publication is Investigational New Drugs (2018), 36(3), 396-406, database is CAplus and MEDLINE.

The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing’s sarcoma cells to tenovin-1. We examined its effects in two Ewing’s sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting. Tenovin-1 elicited caspase-mediated cell death in p53 wild-type cells, but caspase-independent cell death in p53 null cells. Remarkably, it induced a nonlinear concentration response in the latter: low concentrations of tenovin-1 were much more effective than were higher concentrations Tenovin-1’s effects in p53 null cells involved gene expression changes of Bcl-2 family members, mitochondrial membrane depolarization, nuclear translocation of apoptosis-inducing factor, ROS formation and DNA damage; all these effects followed a bell-shaped pattern. In conclusion, our results provide new insights into tenovin-1’s mode of action by demonstrating that it can induce different pathways of cell death.

Investigational New Drugs 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, HPLC of Formula: 380315-80-0.

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

Marx-Blumel, Lisa published the artcileAssessment of HDACi-induced cytotoxicity, Computed Properties of 380315-80-0, the publication is Methods in Molecular Biology (New York, NY, United States) (2017), 23-45, database is CAplus and MEDLINE.

A review. The chromatin contains the genetic and the epigenetic information of a eukaryotic organism. Posttranslational modifications of histones, such as acetylation and methylation, regulate their structure and control gene expression. Histone acetyltransferases (HATs) acetylate lysine residues in histones while histone deacetylases (HDACs) remove this modification. HDAC inhibitors (HDACi) can alter gene expression patterns and induce cytotoxicity in cancer cells. Here we provide an overview of methods to determine the cytotoxic effects of HDACi treatment. Our chapter describes colorimetric methods, like trypan blue exclusion test, crystal violet staining, lactate dehydrogenase assay, MTT and Alamar Blue assays, as well as fluorogenic methods like TUNEL staining and the caspase-3/7 activity assay. Moreover, we summarize flow cytometric anal. of propidium iodide uptake, annexin V staining, cell cycle status, ROS levels, and mitochondrial membrane potential as well as detection of apoptosis by Western blot.

Methods in Molecular Biology (New York, NY, United States) 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

Sonnemann, J. published the artcilep53-dependent and p53-independent anticancer effects of different histone deacetylase inhibitors, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is British Journal of Cancer (2014), 110(3), 656-667, database is CAplus and MEDLINE.

Background: Histone deacetylase inhibitors (HDACi) are promising antineoplastic agents, but their precise mechanisms of actions are not well understood. In particular, the relevance of p53 for HDACi-induced effects has not been fully elucidated. We investigated the anticancer effects of four structurally distinct HDACi, vorinostat, entinostat, apicidin and valproic acid, using isogenic HCT-116 colon cancer cell lines differing in p53 status. Methods: Effects were assessed by MTT assay, flow-cytometric analyses of propidium iodide uptake, mitochondrial depolarisation and cell-cycle distribution, as well as by gene expression profiling. Results: Vorinostat was equally effective in p53 wild-type and null cells, whereas entinostat was less effective in p53 null cells. Histone deacetylase inhibitors treatment suppressed the expression of MDM2 and increased the abundance of p53. Combination treatments showed that vorinostat enhanced the cytotoxic activity of TRAIL and bortezomib, independent of the cellular p53 status. Investigations into the effects of an inhibitor of the sirtuin class of HDAC, tenovin-1, revealed that tenovin-1-mediated cell death hinged on p53. Conclusion: These results demonstrate that vorinostat activates p53, but does not require p53 for inducing its anticancer action. Yet they also demonstrate that entinostat-induced cytotoxic effects partially depend on p53, indicating that different HDACi have a different requirement for p53.

British Journal of Cancer 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 C23H43NP2, Application of N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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