Category: amides-buliding-blocks

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

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

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

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

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

Venkappayya, D. published the artcile“4-Morpholinyl-(thiocarbonic) acid amide” [thio-4-morpholinecarboxamide], Application In Synthesis of 14294-10-1, the publication is Current Science (1969), 38(7), 155-6, database is CAplus.

The procedure of Henry and Dehn (1950) for the reaction of morpholine HCl salt and KSCN was repeated and gave a compound m. 112.5-15.5°, as previously reported. However, aqueous solutions of this compound gave an intense red color with acidic ferric ion solutions, and ion exchange confirmed the presence of morpholinium and thiocyanate ions. The ir spectrum of the solid compound showed bands characteristic of C-N and C-S stretching modes in ionic thiocyanates. On the basis of these experiments, the compound was thought to be morpholinium thiocyanate rather than thio-4-morpholinecar-boxamide.

Current 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 C20H19NO4, Application In Synthesis of 14294-10-1.

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

Ban, Jozef published the artcileSuppression of Deacetylase SIRT1 Mediates Tumor-Suppressive NOTCH Response and Offers a Novel Treatment Option in Metastatic Ewing Sarcoma, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Cancer Research (2014), 74(22), 6578-6588, database is CAplus and MEDLINE.

These findings offer a mechanistic rationale for the use of pharmacol. inhibitors of a p53 deacetylase to treat cancers in which NOTCH acts a tumor suppressor. The developmental receptor NOTCH plays an important role in various human cancers as a consequence of oncogenic mutations. Here we describe a novel mechanism of NOTCH-induced tumor suppression involving modulation of the deacetylase SIRT1, providing a rationale for the use of SIRT1 inhibitors to treat cancers where this mechanism is inactivated because of SIRT1 overexpression. In Ewing sarcoma cells, NOTCH signaling is abrogated by the driver oncogene EWS-FLI1. Restoration of NOTCH signaling caused growth arrest due to activation of the NOTCH effector HEY1, directly suppressing SIRT1 and thereby activating p53. This mechanism of tumor suppression was validated in Ewing sarcoma cells, B-cell tumors, and human keratinocytes where NOTCH dysregulation has been implicated pathogenically. Notably, the SIRT1/2 inhibitor Tenovin-6 killed Ewing sarcoma cells in vitro and prohibited tumor growth and spread in an established xenograft model in zebrafish. Using immunohistochem. to analyze primary tissue specimens, we found that high SIRT1 expression was associated with Ewing sarcoma metastasis and poor prognosis. Our findings suggest a mechanistic rationale for the use of SIRT1 inhibitors being developed to treat metastatic disease in patients with Ewing sarcoma. Cancer Res; 74(22); 6578-88. ©2014 AACR.

Cancer Research 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

Saleh, Amer F. published the artcileSynthesis and Splice-Redirecting Activity of Branched, Arginine-Rich Peptide Dendrimer Conjugates of Peptide Nucleic Acid Oligonucleotides, Synthetic Route of 186046-83-3, the publication is Bioconjugate Chemistry (2010), 21(10), 1902-1911, database is CAplus and MEDLINE.

Arginine-rich cell-penetrating peptides have found excellent utility in cell and in vivo models for enhancement of delivery of attached charge-neutral PNA or PMO oligonucleotides. The authors report the synthesis of dendrimeric peptides containing 2- or 4-branched arms each having one or more R-Ahx-R (R = Arg; Ahx = aminohexanoic acid) motifs and their disulfide conjugation to a PNA705 splice-redirecting oligonucleotide. Conjugates were assayed in a HeLa pLuc705 cell assay for luciferase up-regulation and splicing redirection. Whereas 8-Arg branched peptide-PNA conjugates showed poor activity compared to a linear (R-Ahx-R)₄-PNA conjugate, 2-branched and some 4-branched 12 and 16 Arg peptide-PNA conjugates showed activity similar to that of the corresponding linear peptide-PNA conjugates. Many of the 12- and 16-Arg conjugates retained significant activity in the presence of serum. Evidence showed that biol. activity in HeLa pLuc705 cells of the PNA conjugates of branched and linear (R-Ahx-R) peptides is associated with an energy-dependent uptake pathway, predominantly clathrin-dependent, but also with some caveolae dependence.

Bioconjugate Chemistry 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, Synthetic Route of 186046-83-3.

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

Deuss, Peter J. published the artcileParallel synthesis and splicing redirection activity of cell-penetrating peptide conjugate libraries of a PNA cargo, HPLC of Formula: 186046-83-3, the publication is Organic & Biomolecular Chemistry (2013), 11(43), 7621-7630, database is CAplus and MEDLINE.

A novel method for the parallel synthesis of peptide-biocargo conjugates was developed that utilizes affinity purification for fast isolation of the conjugates in order to avoid time consuming HPLC purification The methodol. was applied to create two libraries of cell-penetrating peptide (CPP)-PNA705 conjugates from parallel-synthesized peptide libraries. The conjugates were tested for their ability to induce splicing redirection in HeLa pLuc705 cells. The results demonstrate how the novel methodol. can be applied for screening purposes in order to find suitable CPP-biocargo combinations and further optimization of CPPs.

Organic & Biomolecular Chemistry 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

Suzuki, Toru published the artcileSwitchable genome editing via genetic code expansion, Safety of H-Lys(Boc)-OH, the publication is Scientific Reports (2018), 8(1), 1-12, database is CAplus and MEDLINE.

Multiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation and Cas9 variants have accordingly been generated whose activity responds to small ligands, temperature or light. However, these approaches are often impracticable, for example in clin. therapeutic genome editing in situ or gene drives in which environmentally-compatible control is paramount. With this in mind, we have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by the cheap lysine derivative, Lys(Boc) (BOC). Genetic code expansion permitted non-physiol. BOC incorporation such that Cas9 (Cas9^BOC) was expressed in a full-length, active form in cultured somatic cells only after BOC exposure. Stringently BOC-dependent, heritable editing of transgenic and native genomic loci occurred when Cas9^BOC was expressed at the onset of mouse embryonic development from cRNA or Cas9^BOC transgenic females. The tightly controlled Cas9 editing system reported here promises to have broad applications and is a first step towards purposed, spatiotemporal gene drive regulation over large geog. ranges.

Scientific Reports 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 C9H10O3S, Safety of H-Lys(Boc)-OH.

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