Month: November 2022

Miyamura, Shin published the artcileC-H activation enables a rapid structure-activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors, Formula: C14H20BNO3, the publication is Organic & Biomolecular Chemistry (2016), 14(36), 8576-8585, database is CAplus and MEDLINE.

We describe the structure-activity relation of various arylcyclopropylamines (ACPAs), which are potent LSD1 inhibitors. More than 45 ACPAs were synthesized rapidly by an unconventional method that we have recently developed, consisting of a C-H borylation and cross-coupling sequence starting from cyclopropylamine. We also generated NCD38 derivatives, which are known as LSD1 selective inhibitors, and discovered a more effective inhibitor compared to the original NCD38.

Organic & Biomolecular Chemistry published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, Formula: C14H20BNO3.

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

Sunami, Yoshitaka published the artcileInhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is PLoS One (2013), 8(2), e57633, database is CAplus and MEDLINE.

Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL) cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated α-tubulin, a major SIRT2 substrate. Unlike the clin. used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia-retinoic acid receptor α (PML-RAR-α) stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-α activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-α does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation.

PLoS One 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 C18H10, 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

Netzeva, Tatiana I. published the artcileDescription of the Electronic Structure of Organic Chemicals Using Semiempirical and Ab Initio Methods for Development of Toxicological QSARs, Recommanded Product: 2,4-Dichlorobenzamide, the publication is Journal of Chemical Information and Computer Sciences (2005), 45(1), 106-114, database is CAplus and MEDLINE.

The quality of quant. structure-activity relationship (QSAR) models depends on the quality of their constitutive elements including the biol. activity, statistical procedure applied, and the physicochem. and structural descriptors. The aim of this study was to assess the comparative use of ab initio and semiempirical quantum chem. calculations for the development of toxicol. QSARs applied to a large and chem. diverse data set. A heterogeneous collection of 568 organic compounds with 96 h acute toxicity measured to the fish fathead minnow (Pimephales promelas) was utilized. A total of 162 descriptors were calculated using the semiempirical AM1 Hamiltonian, and 121 descriptors were compiled using an ab initio (B3LYP/6-31G**) method. The QSARs were derived using multiple linear regression (MLR) and partial least squares (PLS) analyses. Statistically similar models were obtained using AM1 and B3LYP calculated descriptors supported by the use of the logarithm of the octanol-water partition coefficient (log K_ow). The main difference between the models derived by both MLR and PLS with the two sets of quantum chem. descriptors was concentrated on the type of descriptors selected. It was concluded that for large-scale predictions, irresp. of the mechanism of toxic action, the use of precise but time-consuming ab initio methods does not offer considerable advantage compared to the semiempirical calculations and could be avoided.

Journal of Chemical Information and Computer Sciences 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, Recommanded Product: 2,4-Dichlorobenzamide.

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

Mojeiko, Gabriela published the artcileOptimization of nanoemulsified systems containing lamellar phases for co-delivery of celecoxib and endoxifen to the skin aiming for breast cancer chemoprevention and treatment, Quality Control of 169590-42-5, the publication is Colloids and Surfaces, A: Physicochemical and Engineering Aspects (2022), 128901, database is CAplus.

We proposed an innovative nanoemulsified system containing lamellar phases (NLP) produced by a low-energy method to enable the local-transdermal co-delivery of celecoxib and endoxifen as a potential strategy for breast cancer local chemoprevention. The NLPs were composed of surfactant:oil phase at 1:1 (weight/weight) and 80% water. Oleic or caprylic acid was added (2% or 5% weight/weight) as penetration enhancer. NLP droplet size was influenced by the type and concentration of the penetration enhancer, ranging from 290 to 450 nm with neg. zeta potential. They presented pseudoplastic behavior, and after drug addition, elastic and bioadhesive properties were displayed. Compared to water (control), all formulations increased transepidermal water loss by 8.5-12.9 times, with the NLP containing 5% oleic acid promoting a more pronounced effect. No signs of vascular toxicity were observed in the HET-CAM model, suggesting safety. All NLPs increased the penetration of celecoxib and endoxifen in the skin, but the formulation containing 5% oleic acid was more effective, promoting ∼ 3-22-fold increases in cutaneous delivery and ∼ 11-20-fold increases in transdermal drug delivery. Combination of celecoxib and endoxifen in this NE reduced the viability of cancer cells in a synergistic manner compared to the use of isolated drugs. These results suggest the potential applicability of the NE for topical delivery and breast cancer chemoprevention.

Colloids and Surfaces, A: Physicochemical and Engineering Aspects 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 C17H14F3N3O2S, Quality Control of 169590-42-5.

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

Mochizuki, Tatsuki published the artcilePhysiologically-based pharmacokinetic model-based translation of OATP1B -mediated drug-drug interactions from coproporphyrin I to probe drugs, COA of Formula: C24H29N5O3, the publication is Clinical and Translational Science (2022), 15(6), 1519-1531, database is CAplus and MEDLINE.

The accurate prediction of OATP1B-mediated drug-drug interactions (DDIs) is challenging for drug development. Here, we report a physiol.-based pharmacokinetic (PBPK) model anal. for clin. DDI data generated in heathy subjects who received oral doses of cyclosporin A (CysA; 20 and 75 mg) as an OATP1B inhibitor, and the probe drugs (pitavastatin, rosuvastatin, and valsartan). PBPK models of CysA and probe compounds were combined assuming inhibition of hepatic uptake of endogenous coproporphyrin I (CP-I) by CysA. In vivo K_i of unbound CysA for OATP1B (K_i,OATP1B), and the overall intrinsic hepatic clearance per body weight of CP-I (CL_int,all,unit) were optimized to account for the CP-I data (K_i,OATP1B, 0.536 ± 0.041 nM; CL_int,all,unit, 41.9 ± 4.3 L/h/kg). DDI simulation using K_i,OATP1B reproduced the dose-dependent effect of CysA (20 and 75 mg) and the dosing interval (1 and 3 h) on the time profiles of blood concentrations of pitavastatin and rosuvastatin, but DDI simulation using in vitro K_i,OATP1B failed. The Cluster Gauss-Newton method was used to conduct parameter optimization using 1000 initial parameter sets for the seven pharmacokinetic parameters of CP-I (β, CL_int,all, F_aF_g, R_dif, f_bile, f_syn, and v_syn), and K_i,OATP1B and K_i,MRP2 of CysA. Based on the accepted 546 parameter sets, the range of CL_int,all and K_i,OATP1B was narrowed, with coefficients of variation of 12.4% and 11.5%, resp., indicating that these parameters were practically identifiable. These results suggest that PBPK model anal. of CP-I is a promising translational approach to predict OATP1B-mediated DDIs in drug development.

Clinical and Translational Science 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

Mohi El-Deen, Eman M. published the artcileNovel Pyridothienopyrimidine Derivatives: Design, Synthesis and Biological Evaluation as Antimicrobial and Anticancer Agents, Recommanded Product: 2-Chloroacetamide, the publication is Molecules (2022), 27(3), 803, database is CAplus and MEDLINE.

The growing risk of antimicrobial resistance besides the continuous increase in the number of cancer patients represents a great threat to global health, which requires intensified efforts to discover new bioactive compounds to use as antimicrobial and anticancer agents. Thus, a new set of pyridothienopyrimidine derivatives 2a,b-9a,b was synthesized via cyclization reactions of 3-amino-thieno[2,3-b]pyridine-2-carboxamides 1a,b with different reagents. All new compounds were evaluated against five bacterial and five fungal strains. Many of the target compounds showed significant antimicrobial activity. In addition, the new derivatives were further subjected to cytotoxicity evaluation against HepG-2 and MCF-7 cancer cell lines. The most potent cytotoxic candidates (3a, 4a, 5a, 6b, 8b and 9b) were examined as EGFR kinase inhibitors. Mol. docking study was also performed to explore the binding modes of these derivatives at the active site of EGFR-PK. Compounds 3a, 5a and 9b displayed broad spectrum antimicrobial activity with MIC ranges of 4-16 μg/mL and potent cytotoxic activity with IC₅₀ ranges of 1.17-2.79 μM. In addition, they provided suppressing activity against EGFR with IC₅₀ ranges of 7.27-17.29 nM, higher than that of erlotinib, IC₅₀ = 27.01 nM.

Molecules 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, Recommanded Product: 2-Chloroacetamide.

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

Arvaniti, Olga S. published the artcileSorption of two common antihypertensive drugs onto polystyrene microplastics in water matrices, Formula: C24H29N5O3, the publication is Science of the Total Environment (2022), 155786, database is CAplus and MEDLINE.

Recent studies have shown the widespread occurrence of microplastics in multiple environmental compartments. When discharged into the aquatic environment, microplastics interact with other chems. acting as vectors of organic and inorganic micropollutants. In the present study, we examined the sorption of two commonly used antihypertensive drugs, valsartan (VAL) and losartan (LOS), onto polystyrene (PS) microplastics and we studied the effects of water matrix, solution’s pH, salinity, and microplastics’ aging on their sorption. According to the results, the sorption of VAL and LOS onto PS is a slow process that reaches equilibrium after 12 days. The sorption of both target micropollutants was pH-dependent and significantly decreased under alk. conditions. The removal of VAL was enhanced in the presence of 100 mM of Ca²⁺ while no statistical significant effects were observed when Na⁺ was added. The increase of salinity either did not affect or decreased the removal of LOS. Lower sorption of both drugs was observed when aged PS was used despite that the sp. surface area for aged PS was 39% higher than pristine. Calculation of the sorption distribution coefficient (Kd) for different water matrixes showed that the increase of matrix complexity inhibited target compounds’ removal and the sorption rate decreased from bottled water > river water ≈ treated wastewater for the two compounds For VAL, the Kd values ranged between 795 ± 63 L/kg (bottled water) and 384 ± 88 L/kg (river water), while for LOS between 4453 ± 417 L/kg (bottled water) and 3078 ± 716 L/kg (treated wastewater). Both VAL and LOS sorption onto PS microplastics can be described by hydrophobic and electrostatic interactions. The current results indicate that PS particles could affect the transportation of antihypertensive drugs in the aquatic environment causing potential adverse effects on the environment and public health.

Science of the Total Environment 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

Alanine, Alexander published the artcileSynthesis and SAR evaluation of 1,2,4-triazoles as A_2A receptor antagonists, Computed Properties of 64559-06-4, the publication is Bioorganic & Medicinal Chemistry Letters (2004), 14(3), 817-821, database is CAplus and MEDLINE.

The synthesis and in vitro structure-activity relationships (SAR) of a series of triazoles as A_2A receptor antagonists is reported. This resulted in the identification of potent, selective and permeable 1,2,4-triazoles such as 3-(3,4-dimethylbenzyl)-5-(3-methoxyphenyl)-1,2,4-triazole for further optimization and evaluation in vivo.

Bioorganic & Medicinal Chemistry Letters 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, Computed Properties of 64559-06-4.

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

Bahadorikhalili, Saeed published the artcileMo (CO)₆-assisted Pd-supported magnetic graphene oxide-catalyzed carbonylation-cyclization as an efficient way for the synthesis of 4(3H)-quinazolinones, Application of 3-Methoxybenzothioamide, the publication is Applied Organometallic Chemistry (2019), 33(4), n/a, database is CAplus.

A novel catalyst was introduced based on the immobilization of palladium on modified magnetic graphene oxide nanoparticles. The catalyst was characterized by several methods, including transmission electron microscopy, SEM, X-ray fluorescence, vibrating-sample magnetometer, Fourier transform-IR and dynamic light scattering (DLS) anal. The activity of the catalyst was investigated in the synthesis of 4(3H)-quinazolinones via Pd-catalyzed carbonylation-cyclization of N-(2-bromoaryl) benzimidamides by Mo(CO)₆. The Mo(CO)₆ was used as a carbon monoxide source for performing the reaction under mild conditions. The catalyst showed good reusability and no change in activity was observed after 10 cycles of recovery.

Applied Organometallic Chemistry 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, Application of 3-Methoxybenzothioamide.

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

Zhang, Xin published the artcileSynthesis of chiral sulfinate esters by asymmetric condensation, COA of Formula: C17H14F3N3O2S, the publication is Nature (London, United Kingdom) (2022), 604(7905), 298-303, database is CAplus and MEDLINE.

Here a straightforward access to enantioenriched sulfinate esters via asym. condensation of prochiral sulfinates and alcs. using pentanidium as an organocatalyst was reported. This study successfully coupled a wide range of sulfinates and bioactive alcs. stereoselectively. The initial sulfinates was prepared from existing sulfone and sulfonamide drugs and the resulting sulfinate esters were versatile for transformations to diverse chiral sulfur pharmacophores. Through late-stage diversification 11,12 of celecoxib and other drug derivatives, was demonstrate the viability of this unified approach towards sulfur stereogenic centers.

Nature (London, United Kingdom) 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 C15H15OP, COA of Formula: C17H14F3N3O2S.

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