Month: December 2022

Lerchen, Hans-Georg published the artcileAntibody-Drug Conjugates with Pyrrole-Based KSP Inhibitors as the Payload Class, Name: (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)-5-ureidopentanoic acid, the publication is Angewandte Chemie, International Edition (2018), 57(46), 15243-15247, database is CAplus and MEDLINE.

The number of cytotoxic payload classes successfully employed in antibody-drug conjugates (ADCs) is still rather limited. The identification of ADC payloads with a novel mode of action will increase therapeutic options and potentially increase the therapeutic window. Herein, the authors describe the utilization of kinesin spindle protein inhibitors (KSPi) as a novel payload class providing highly potent ADCs against different targets, for instance HER-2 or TWEAKR/Fn14. Aspects of tech. optimization include the development of different linker attachment sites, the stabilization of ADC linkage to avoid payload deconjugation and finally, the tailor-made design of active metabolites with a long lasting intracellular exposure in the tumor matching the mode of action of KSP inhibition. These KSPi-ADCs are highly potent and selective in vitro and demonstrate in vivo efficacy in a broad panel of tumor models including complete regressions in a patient-derived urothelial cancer model.

Angewandte Chemie, International Edition 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, Name: (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

Sigurdardottir, A. G. published the artcileExploring the chemical space of the lysine-binding pocket of the first kringle domain of hepatocyte growth factor/scatter factor (HGF/SF) yields a new class of inhibitors of HGF/SF-MET binding, Safety of Morpholine-4-carbothioamide, the publication is Chemical Science (2015), 6(11), 6147-6157, database is CAplus and MEDLINE.

The growth/motility factor hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the tyrosine kinase MET, constitute a signalling system essential for embryogenesis and for tissue/organ regeneration in post-natal life. HGF/SF-MET signalling, however, also plays a key role in the onset of metastasis of a large number of human tumors. Both HGF/SF and MET are high mol. weight proteins that bury an extensive interface upon complex formation and thus constitute a challenging target for the development of low mol. weight inhibitors. Here we have used surface plasmon resonance (SPR), NMR (NMR) and X-ray crystallog. to screen a diverse fragment library of 1338 members as well as a range of piperazine-like compounds Several small mols. were found to bind in the lysine-binding pocket of the kringle 1 domain of HGF/SF and its truncated splice variant NK1. We have defined the binding mode of these compounds, explored their biol. activity and we show that selected fragments inhibit MET downstream signalling. Thus we demonstrate that targeting the lysine-binding pocket of NK1 is an effective strategy to generate MET receptor antagonists and we offer proof of concept that the HGF/SF-MET interface may be successfully targeted with small mols. These studies have broad implications for the development of HGF/SF-MET therapeutics and cancer treatment.

Chemical Science 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, Safety of Morpholine-4-carbothioamide.

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

Unni, Aparna Beena published the artcileVapor-Deposited Thin Films: Studying Crystallization and α-relaxation Dynamics of the Molecular Drug Celecoxib, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Journal of Physical Chemistry B (2022), 126(20), 3789-3798, database is CAplus and MEDLINE.

Crystallization is one of the major challenges in using glassy solids for technol. applications. Considering pharmaceutical drugs, maintaining a stable amorphous form is highly desirable for improved solubility Glasses prepared by the phys. vapor deposition technique got attention because they possess very high stability, taking thousands of years for an ordinary glass to achieve. In this work, we have investigated the effect of reducing film thickness on the α-relaxation dynamics and crystallization tendency of vapor-deposited films of celecoxib (CXB), a pharmaceutical substance. We have scrutinized its crystallization behavior above and below the glass-transition temperature (T_g). Even though vapor deposition of CXB cannot inhibit crystallization completely, we found a significant decrease in the crystallization rate with decreasing film thickness. Finally, we have observed striking differences in relaxation dynamics of vapor-deposited thin films above the T_g compared to spin-coated counterparts of the same thickness.

Journal of Physical Chemistry B published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C3H9ClOS, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Dunkelmann, Daniel L. published the artcileEngineered triply orthogonal pyrrolysyl-tRNA synthetase/tRNA pairs enable the genetic encoding of three distinct non-canonical amino acids, Synthetic Route of 2418-95-3, the publication is Nature Chemistry (2020), 12(6), 535-544, database is CAplus and MEDLINE.

Expanding and reprogramming the genetic code of cells for the incorporation of multiple distinct non-canonical amino acids (ncAAs), and the encoded biosynthesis of non-canonical biopolymers, requires the discovery of multiple orthogonal aminoacyl-tRNA synthetase/tRNA pairs. These pairs must be orthogonal to both the host synthetases and tRNAs and to each other. Pyrrolysyl-tRNA synthetase (PylRS)/^PyltRNA pairs are the most widely used system for genetic code expansion. Here, we reveal that the sequences of ΔNPylRS/^ΔNPyltRNA pairs (which lack N-terminal domains) form two distinct classes. We show that the measured specificities of the ΔNPylRSs and ^ΔNPyltRNAs correlate with sequence-based clustering, and most ΔNPylRSs preferentially function with ^ΔNPyltRNAs from their class. We then identify 18 mutually orthogonal pairs from the 88 ΔNPylRS/^ΔNPyltRNA combinations tested. Moreover, we generate a set of 12 triply orthogonal pairs, each composed of three new PylRS/^PyltRNA pairs. Finally, we diverge the ncAA specificity and decoding properties of each pair, within a triply orthogonal set, and direct the incorporation of three distinct non-canonical amino acids into a single polypeptide.

Nature 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, Synthetic Route of 2418-95-3.

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

Sanz Sharley, Daniel D. published the artcileA selective hydration of nitriles catalyzed by a Pd(OAc)₂-based system in water, SDS of cas: 2447-79-2, the publication is Tetrahedron Letters (2017), 58(43), 4090-4093, database is CAplus.

In situ formation of a [Pd(OAc)₂bipy] (bipy = 2,2′-bipyridyl) complex in water selectively catalyzes the hydration of a wide range of organonitriles at 70°. Catalyst loadings of 5 mol% afford primary amide products RC(O)NH₂ (R = Et, n-Pr, C₆H₅, etc.) in excellent yields in the absence of hydration-promoting additives such as oximes and hydroxylamines.

Tetrahedron Letters 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 C7H5Cl2NO, SDS of cas: 2447-79-2.

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

Kario, Kazuomi published the artcileAngiotensin receptor-neprilysin inhibitors for hypertension-hemodynamic effects and relevance to hypertensive heart disease, Formula: C24H29N5O3, the publication is Hypertension Research (2022), 45(7), 1097-1110, database is CAplus and MEDLINE.

A review. Angiotensin receptor-neprilysin inhibitors have multiple beneficial effects on the cardiovascular system. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to effectively reduce ambulatory 24-h blood pressure in patients with hypertension, and improvements in many aspects of hemodynamic function have also been reported. Overall hemodynamic effects on arterial stiffness and nocturnal blood pressure play an important role in the pathogenesis of hypertensive heart disease. Therefore, these could represent mechanistic targets underlying the effects of angiotensin receptor-neprilysin inhibitors on the continuum of cardiovascular disease from hypertension to heart failure. Other potential mechanisms include reductions in circulating volume and sympathetic activity, both of which contribute to the protection against target organ damage and pos. changes in cardiac biomarkers seen during angiotensin receptor-neprilysin inhibitor therapy. The mechanisms of action and beneficial effects of angiotensin receptor-neprilysin inhibitors are complementary to those of a number of other treatment options for hypertension, suggesting the possibility of additive or even synergistic benefits. Based on available data, there are a number of patient groups who will benefit from antihypertensive treatment with an angiotensin receptor-neprilysin inhibitor, including those with salt-sensitive hypertension, structural hypertension, resistant hypertension, and hypertension in the presence of heart failure. Overall, angiotensin receptor-neprilysin inhibitors regulate blood pressure and pulse pressure via multiple mechanisms and provide cardiovascular protection. This provides an option for effective intervention early in the vicious cycle of elevated blood pressure and central pressures with progression toward heart failure that should help to address the growing worldwide heart failure epidemic.

Hypertension Research 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, Formula: C24H29N5O3.

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

Pierens, Raymond K. published the artcileThe dipole moments, molar Kerr constants, and solution-state conformation of some substituted benzamides, HPLC of Formula: 2447-79-2, the publication is Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) (1980), 235-8, database is CAplus.

The dipole moments and molar Kerr constants were determined for 24 substituted benzamides in dioxane, and discussed in relation to preferred solution conformations. The results indicate that for a given ring substituent the dihedral angle between the planar amide group and the benzene ring is similar for both the 3- and 4-substituted benzamides but less than that for the 2-substituted isomer. For the 3-substituted benzamides both cis and trans conformers contribute to the observed dipole moment and molar Kerr constant whereas for the 2-substituted species only that conformer contributes which has the amide C:O bond remote from the ortho substituent.

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) 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 C7H5Cl2NO, HPLC of Formula: 2447-79-2.

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

Wall, Brendan J. published the artcileImportance of Hydrogen Bonding: Structure-Activity Relationships of Ruthenium(III) Complexes with Pyridine-Based Ligands for Alzheimer′s Disease Therapy, Formula: C6H6N2O, the publication is Journal of Medicinal Chemistry (2021), 64(14), 10124-10138, database is CAplus and MEDLINE.

Alzheimer′s disease (AD) is the most common form of dementia, where one of the pathol. hallmarks of AD is extracellular protein deposits, the primary component of which is the peptide amyloid-β (Aβ). Recently, the soluble form of Aβ has been recognized as the primary neurotoxic species, making it an important target for therapeutic development. Metal-based drugs are promising candidates to target Aβ, as the interactions with the peptide can be tuned by ligand design. In the current study, 11 ruthenium complexes containing pyridine-based ligands were prepared, where the functional groups at the para position on the coordinated pyridine ligand were varied to determine structure-activity relationships. Overall, the complexes with terminal primary amines had the greatest impact on modulating the aggregation of Aβ and diminishing its cytotoxicity. These results identify the importance of specific intermol. interactions and are critical in the advancement of metal-based drugs for AD therapy.

Journal of Medicinal 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 C13H10F2, Formula: C6H6N2O.

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

Apgar, James M. published the artcileIbrexafungerp: An orally active β-1,3-glucan synthesis inhibitor, Name: Isonicotinamide, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 127661, database is CAplus and MEDLINE.

We previously reported medicinal chem. efforts that identified MK-5204 (I), an orally efficacious β-1,3-glucan synthesis inhibitor derived from the natural product enfumafungin. Further extensive optimization of the C2 triazole substituent identified 4-pyridyl as the preferred replacement for the carboxamide of MK-5204, leading to improvements in antifungal activity in the presence of serum, and increased oral exposure. Reoptimizing the aminoether at C3 in the presence of this newly discovered C2 substituent, confirmed that the (R) t-Bu, Me aminoether of MK-5204 provided the best balance of these two key parameters, culminating in the discovery of ibrexafungerp (II), which is currently in phase III clin. trials. Ibrexafungerp displayed significantly improved oral efficacy in murine infection models, making it a superior candidate for clin. development as an oral treatment for Candida and Aspergillus infections.

Bioorganic & Medicinal Chemistry Letters 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 C6H6N2O, Name: Isonicotinamide.

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

Lawrence, Elliot J. published the artcile3-Aryl-3-(trifluoromethyl)diazirines as Versatile Photoactivated “Linker” Molecules for the Improved Covalent Modification of Graphitic and Carbon Nanotube Surfaces, Product Details of C6H10F3NO, the publication is Chemistry of Materials (2011), 23(16), 3740-3751, database is CAplus.

3-Aryl-3-(trifluoromethyl)diazirines are shown to be synthetically useful photoactivated carbene precursors that can be used as mol. “tethers” to facilitate the improved covalent surface modification of graphitic carbon and carbon nanotubes with a potentially large variety of chem. species. Proof-of-concept is demonstrated by the synthesis, as well as spectroscopic and electrochem. characterization, followed by photoactivated attachment of the organometallic diazirine derivative, 3-[3-(trifluoromethyl)diazirin-3-yl]phenyl ferrocene monocarboxylate, to the surface of vitreous carbon, and also to two different morphologies of multiwalled carbon nanotubes (“bamboo-like” and “hollow-tube”, denoted as b-MWCNTs and h-MWCNTs, resp.). The latter differ only in the relative amounts of “edge-plane-like” defect sites (at the termini of the nanotubes) and “basal-plane-like” pristine sidewall regions. The facile covalent coupling of the ferrocenyl “probe” moiety to the diazirine “linker” was confirmed by UV-vis, ¹H and ¹⁹F NMR spectroscopy, and cyclic voltammetry (CV). Upon exposure to UV irradiation in the presence of graphitic materials, the resulting covalent surface attachment of the ferrocenyl groups via the diazirine “linker” was characterized by Raman and XPS and by CV experiments performed in nonaqueous electrolyte. The surface coverage of 3-[3-(trifluoromethyl)diazirin-3-yl]phenyl ferrocene monocarboxylate, analyzed from both CV and XPS experiments was found to be 7%-11% of that estimated for a complete monolayer, and was 20-fold greater than that achieved in control experiments that employed conventional covalent modification strategies to form esters between ferrocene methanol and surface carboxylate groups on the graphitic materials. The surface loading of ferrocene groups on the b-MWCNTs was found to be only ca. 60%-70% that achieved on h-MWCNTs, reflecting the ability of the functionalized carbene intermediate formed upon photolysis of the parent diazirine to insert into C=C bonds in the otherwise relatively inert sidewalls of the nanotubes. This was further confirmed by Raman spectroscopic characterization, which revealed that the h-MWCNTs experienced significantly more sidewall functionalization than the b-MWCNTs, yet still retained good electronic conduction in electrochem. experiments The relative chem. stability of 3-aryl-3-(trifluoromethyl)diazirines, the ease with which they can be potentially be coupled to a large range of different organic, inorganic, and biol. species, and the enhanced surface loading that can be achieved as a result of the reactive carbene intermediate formed during their photolysis, render diazirines highly versatile and potent “linker” mols. for the development of chem. modified materials.

Chemistry of Materials 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 C6H10F3NO, Product Details of C6H10F3NO.

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