Month: December 2022

Dai, Xia-Lin published the artcileSolubility and Permeability Improvement of Allopurinol by Cocrystallization, Category: amides-buliding-blocks, the publication is Crystal Growth & Design (2020), 20(8), 5160-5168, database is CAplus.

Allopurinol is a xanthine oxidase inhibitor with poor solubility and permeability, which severely limit its drug absorption following the administration of some dosage forms, such as tablets and rectal suppositories. To improve the physicochem. properties, three cocrystals of allopurinol with isonicotinamide (ALP-INA), piperazine (ALP-PIP), and 2,4-dihydroxybenzoic acid (ALP-24DHBZA) were successfully prepared by a slurry or liquid-assisted grinding method. The obtained cocrystal materials were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry, and thermogravimetric analyses and were subjected to dynamic vapor sorption, dissolution, and membrane permeability studies. ALP-INA showed solubility and diffusion/membrane permeability similar to those of the parent drug. In contrast, ALP-PIP exhibited improved diffusion/membrane permeability, and ALP-24DHBZA exhibited improved dissolution behavior, resp. These results suggest that ALP-PIP and ALP-24DHBZA have the potential to be developed as new, more efficient formulations of allopurinol. Three cocrystals of allopurinol (ALP) with isonicotinamide (ALP-INA), piperazine (ALP-PIP), and 2,4-dihydroxybenzoic acid (ALP-24DHBZA) were synthesized, and ALP-PIP and ALP-24DHBZA resp. showed significant improvement in membrane permeability and dissolution behaviors in comparison to the original ALP.

Crystal Growth & Design 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, Category: amides-buliding-blocks.

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

Wang, Lei published the artcileStructures of the Human PGD₂ Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition, Safety of [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Molecular Cell (2018), 72(1), 48-59.e4, database is CAplus and MEDLINE.

The signaling of prostaglandin D₂ (PGD₂) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clin. investigation, and one compound, fevipiprant, has advanced to phase 3 clin. trials for asthma. Here, we present the crystal structures of human CRTH2 with two antagonists, fevipiprant and CAY10471. The structures, together with docking and ligand-binding data, reveal a semi-occluded pocket covered by a well-structured amino terminus and different binding modes of chem. diverse CRTH2 antagonists. Structural anal. suggests a ligand entry port and a binding process that is facilitated by opposite charge attraction for PGD₂, which differs significantly from the binding pose and binding environment of lysophospholipids and endocannabinoids, revealing a new mechanism for lipid recognition by GPCRs.

Molecular Cell 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 C25H47NO8, Safety of [(2-Hexylcyclopentylidene)amino]thiourea.

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

Moniruzzaman, Mohammad published the artcileElectrochemical approach to trifluoroacetamide synthesis from 1,1,1-trichloro-2,2,2-trifluoroethane (CFC-113a) catalyzed by B₁₂ complex, HPLC of Formula: 360-92-9, the publication is Journal of Porphyrins and Phthalocyanines (2022), 26(6/7), 419-426, database is CAplus.

One-pot synthetic approach to produce trifluoroacetamide has been developed using an electrochem. method with the B12 complex as a catalyst under mild conditions, in open air at room temperature Thirty examples of trifluoroacetamide were synthesized from 1,1,1-trichloro-2,2,2-trifluoroethane (CFC-113a) in moderate to good yields. This user-friendly strategy is compatible with a broad range of trifluoroacetamide syntheses.

Journal of Porphyrins and Phthalocyanines 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, HPLC of Formula: 360-92-9.

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

Zhong, Yuhua published the artcileNovel ¹⁸F-Labeled Isonicotinamide-Based Radioligands for Positron Emission Tomography Imaging of Glycogen Synthase Kinase-3β, Formula: C6H6N2O, the publication is Molecular Pharmaceutics (2021), 18(3), 1277-1284, database is CAplus and MEDLINE.

Glycogen synthase kinase-3β (GSK-3β), a cytoplasmic serine/threonine protein kinase, is involved in several human pathologies including Alzheimer’s disease, bipolar disorder, diabetes, and cancer. Positron emission tomog. (PET) imaging of GSK-3β could aid in investigating GSK-3β levels under normal and pathol. conditions. In this study, we designed and synthesized fluorinated PET radioligands starting with recently identified isonicotinamide derivatives that showed potent affinity to GSK-3β. After extensive in vitro inhibitory activity assays and analyzing U87 cell uptake, we identified [¹⁸F]10a-d as potential tracers with good specificity and high affinity. They were then subjected to further in vivo evaluation in rodent brain comprising PET imaging and metabolism studies. The radioligands [¹⁸F]10b-d penetrated the blood-brain barrier and accumulated in GSK-3β-rich regions, including amygdala, cerebellum, and hippocampus. Also, it could be specifically blocked using the corresponding standard compounds With these results, this work sets the basis for further development of novel ¹⁸F-labeled GSK-3β PET probes.

Molecular Pharmaceutics 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 C7H11Br, Formula: C6H6N2O.

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

He, Changyu published the artcileDesign and synthesis of redox and oxidative dual responsive block copolymer micelles for intracellular drug delivery, Formula: C4H6F3NOS, the publication is European Polymer Journal (2016), 38-52, database is CAplus.

The need for smart materials in the area of biotechnol. has accelerated the development of stimuli-responsive copolymer micelles. Here, we reported a novel dual-stimuli-responsive block copolymer PEG-DMTK-SS-PLA with both di-Me thioketal (DMTK) and disulfide linkage incorporated into the backbone, capable of triggering fast drug release properties upon both oxidative (H₂O₂) and reductive (GSH) environment. The CMC values of these copolymer micelles ranging from 0.051 to 0.087 mg mL^-1, the average diameters are from 34 nm to 55 nm and 65 nm to 198 nm for blank and DOX-loaded micelles resp. MTT assay conducted in NIH 3T3 cells showed the low cytotoxicity of these micelles even when the concentration reached up to 500 μg/mL. Considering tumor microenvironment’s diverse in kinds of tumor cells, fluorescence microscopy, flow cytometry and MTT activity anal. were conducted in several cancer cells (e.g., cervix, lung, gastric, and colon cancer cells), and further confirmed that the dual responsive PEG-DMTK-SS-PLA micelles were degraded much faster than that of non-responsive PEG-PLA and single responsive PEG-SS-PLA and PEG-DMTK-PLA micelles. These results indicate that the dual-responsive micelles are promising for efficient anticancer drug delivery.

European Polymer Journal published new progress about 1869-45-0. 1869-45-0 belongs to amides-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2,2,2-Trifluoro-N-(2-mercaptoethyl)acetamide, and the molecular formula is C4H6F3NOS, Formula: C4H6F3NOS.

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

Katritzky, Alan R. published the artcileAn efficient conversion of carboxylic acids into Weinreb amides, Name: N-Methoxy-N-methylisonicotinamide, the publication is ARKIVOC (Gainesville, FL, United States) [online computer file] (2002), 39-44, database is CAplus.

Efficient conversions of carboxylic acids into Weinreb amides were achieved by treatment of N-acylbenzotriazoles 2a-i with N,O-dimethylhydroxylamine hydrochloride under mild conditions. No racemization was found when optically active acids were employed.

ARKIVOC (Gainesville, FL, United States) [online computer file] published new progress about 100377-32-0. 100377-32-0 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N-Methoxy-N-methylisonicotinamide, and the molecular formula is C8H10N2O2, Name: N-Methoxy-N-methylisonicotinamide.

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

Fang, Wenjie published the artcileDexamethasone microspheres and celecoxib microcrystals loaded into injectable gels for enhanced knee osteoarthritis therapy, Category: amides-buliding-blocks, the publication is International Journal of Pharmaceutics (Amsterdam, Netherlands) (2022), 121802, database is CAplus and MEDLINE.

The combination of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) has been commonly used for inflammation and chronic articular pain in the clinic. Nonetheless, the long-term administration of both medications might result in osteonecrosis of the knee due to repeated injections of steroids and side effects in the gastrointestinal and cardiovascular systems. To overcome these unmet medical needs, we designed a microsphere-microcrystal-gel delivery system for intra-articular injection. Dexamethasone (DEX)-loaded microspheres (DMs) were optimized by Plackett-Burman and Taguchi orthogonal designs to extend their retention time in the knee joint. Celecoxib (CLX) microcrystals (CMs) were manufactured using an ultrasonic method to improve solubility and bioavailability. Moreover, a green solvent-free method was employed to crosslink and synthesize a novel poloxamer 407/Gantrez S97-based gel system (GZF), which can undergo the sol-gel transition at lower concentrations Then, DM and CM were loaded by GZF to form intra-articular injectable gels (DM/CM/Gel). The in vitro release of DEX and CLX showed a fast phase in 24 h followed by a controlled release of ∼8 d. Both blank microspheres and GZF gels displayed great biocompatibility against RAW264.7 macrophages. The most suitable dosages of 5 nM DEX and 125 nM CLX in the formulation were chosen because of their significant effects against macrophage inflammation with a lower administrative amount An In vivo animal evaluation showed that DM/CM/Gel suppressed the release of inflammatory cytokines (TNF-α and IL-6) after 21 d of treatment. In addition, a histol. evaluation revealed that DM/CM/Gel interrupted the progression of cartilage surface denudation and matrix loss. Therefore, DM/CM/Gel provides a prospective strategy for reforming traditional therapy for chronic articular disease.

International Journal of Pharmaceutics (Amsterdam, Netherlands) 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, Category: amides-buliding-blocks.

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

Wang, Xiaodan published the artcilePreparation of antibacterial polypeptides with different topologies and their antibacterial properties, Application In Synthesis of 2418-95-3, the publication is Biomaterials Science (2022), 10(3), 834-845, database is CAplus and MEDLINE.

Antimicrobial peptides (AMPs) are attractive antimicrobial agents used to combat bacterial infections, and have been advanced to be one of the most promising alternatives to conventional antibiotics. They stand out for their attractive broad-spectrum activity, unmatched antibacterial mechanism that is not prone to develop drug resistance and diversified topologies, which can be fabricated with manifold amino acid blocks. In this study, using n-hexylamine and amine-terminated polyamidoamine dendrimers (Gx-PAMAM, x = 1-2) as initiators, a series of AMPs with linear and star-shaped topol. structures were constructed via the controllable ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs). The antibacterial performances of the tailored linear and star-shaped AMPs were comprehensively evaluated in both solution states and surface-bonded states. The results indicated that the star-shaped AMPs exhibited enhanced bactericidal activity against Gram-neg. E. coli and similar bactericidal activity against Gram-pos. S. aureus when compared with the linear AMPs. It is worth mentioning that star-shaped AMPs demonstrated a significantly faster bactericidal efficiency (completely killed bacteria within 5 min at a concentration of 2 x MIC for S. aureus) than their linear analogs (took 15 min to achieve the same effect). However, when the AMPs were immobilized to the surface, they similarly exhibited superior antibacterial activity and fast bactericidal efficiency towards S. aureus and E. coli in the case of the same surface grafting amount In addition, both the surfaces grafted with AMPs of different topologies demonstrated favorable biocompatibility in vitro.

Biomaterials Science 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 C18H12FN, Application In Synthesis of 2418-95-3.

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

Na, Joo Young published the artcileComparative Pharmacokinetics Between a Fixed-Dose Combination of Pitavastatin/Valsartan 4/160 mg and the Corresponding Individual Components Through a Partial Replicated Crossover Design in Healthy Male Subjects, SDS of cas: 137862-53-4, the publication is Clinical Pharmacology in Drug Development (2022), 11(5), 615-622, database is CAplus and MEDLINE.

Hypertension and hyperlipidemia are often comorbid, requiring combination therapies of antihypertensive drugs and antihyperlipidemia drugs. Taking 1 fixed-dose combination (FDC) may increase patient compliance rather than taking each of the drugs sep. This study aimed to evaluate the pharmacokinetic bioequivalence between an FDC of pitavastatin/valsartan 4/160 mg and the corresponding individual components. Considering that valsartan is a highly variable drug for maximum plasma concentration (C_max), an open-label, randomized, partial replicated crossover study was conducted in 54 healthy subjects. The subjects received a single oral dose of the FDC of pitavastatin/valsartan 4/160 mg in 1 period or the corresponding individual components in the other 2 periods. The geometric mean ratios and their 90%CIs of the FDC to the corresponding individual components for C_max and area under the concentration-time curve from time 0 to the last measurable time point were 1.05 (90%CI, 0.96-1.15) and 0.10 (90%CI, 0.95-1.04) for pitavastatin and 1.15 (90%CI, 1.06-1.25) and 1.06 (0.99-1.14) for valsartan, resp. The geometric mean ratios (90%CIs) for area under the concentration-time curve from time 0 to the last measurable time point and C_max of both drugs were included in the bioequivalence criteria. In conclusion, the FDC of pitavastatin/valsartan 4/160 mg showed pharmacokinetic equivalence with the corresponding individual components.

Clinical Pharmacology in Drug Development 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

Tong, Peng published the artcileHydration of Nitriles to Amides by Thiolate-Bridged Diiron Complexes, Category: amides-buliding-blocks, the publication is Organometallics (2015), 34(14), 3571-3576, database is CAplus.

A series of nitrile-coordinating complexes [Cp*Fe(μ-SEt)RCN]₂[PF₆]₂ (1, R = alkyl, aryl, vinyl, amine) have been obtained by the reaction of [Cp*Fe(μ-SEt)MeCN]₂[PF₆]₂ (1a) with various nitriles in acetone. Complexes 1 can realize the hydration of a nitrile ligand under ambient conditions. Complexes [Cp*Fe(μ-SEt)₂(μ-η¹:η¹-NH(O)CR)FeCp*][PF₆] (2) were successfully isolated as intermediates during the hydration process, with 2b and 2e (R = CH₂:CH and Et₂N) being characterized by spectrometry and X-ray crystallog. Treatment of 2 with HBF₄·Et₂O in the presence of nitriles released corresponding amides 3. At the same time, the structural features of the [Fe₂S₂] scaffold were retained. These results confirmed that the hydration of nitriles was realized by cooperative interaction on diiron centers.

Organometallics published new progress about 2451-91-4. 2451-91-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Benzene, name is N,N-Dibenzylcyanamide, and the molecular formula is C18H24N6O6S4, Category: amides-buliding-blocks.

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