Chemical & pharmaceutical bulletin最新文献_第5页

Synthesis of Coumarin-Conjugated Oligonucleotides via Knoevenagel Condensation to Prepare an Oligonucleotide Library 通过 Knoevenagel 缩合合成香豆素共轭寡核苷酸以制备寡核苷酸库

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00295

Takashi Osawa, Satoshi Obika

{"title":"Synthesis of Coumarin-Conjugated Oligonucleotides via Knoevenagel Condensation to Prepare an Oligonucleotide Library","authors":"Takashi Osawa, Satoshi Obika","doi":"10.1248/cpb.c23-00295","DOIUrl":"https://doi.org/10.1248/cpb.c23-00295","url":null,"abstract":"DNA-encoded libraries (DELs) are attracting attention as a screening tool in the early stages of drug discovery. In the development of DELs, drug candidate compounds are chemically synthesized on barcode DNA. Therefore, it is important to perform the synthesis under mild conditions so as to not damage the DNA. On the other hand, coumarins are gaining increasing research focus not only because they possess excellent fluorescence properties, but also because many medicines contain a coumarin skeleton. Among the various reactions developed for the synthesis of coumarins thus far, Knoevenagel condensation followed by intramolecular cyclization under mild conditions can yield coumarins. In this study, we developed a new synthetic method for preparing a coumarin-conjugated oligonucleotide library via Knoevenagel condensation. The results showed that coumarins substituted at the 5-, 6-, 7-, or 8-positions could be constructed on DNA to afford a total of 26 coumarin-conjugated DNAs. Moreover, this method was compatible with enzymatic ligation, demonstrating its utility in DEL synthesis. The developed strategy for the construction of coumarin scaffolds based on Knoevenagel condensation may contribute to the use of DELs in drug discovery and medicinal chemistry.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00295/figure/72_c23-00295.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rational Design of Amphipathic Antimicrobial Peptides with Alternating L-/D-Amino Acids That Form Helical Structures 合理设计具有交替 L-/D 氨基酸并能形成螺旋结构的两性抗菌肽

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00465

Motoharu Hirano, Hidetomo Yokoo, Nobumichi Ohoka, Takahito Ito, Takashi Misawa, Makoto Oba, Takao Inoue, Yosuke Demizu

{"title":"Rational Design of Amphipathic Antimicrobial Peptides with Alternating L-/D-Amino Acids That Form Helical Structures","authors":"Motoharu Hirano, Hidetomo Yokoo, Nobumichi Ohoka, Takahito Ito, Takashi Misawa, Makoto Oba, Takao Inoue, Yosuke Demizu","doi":"10.1248/cpb.c23-00465","DOIUrl":"https://doi.org/10.1248/cpb.c23-00465","url":null,"abstract":"Antimicrobial peptides (AMPs) are promising therapeutic agents against bacteria. We have previously reported an amphipathic AMP Stripe composed of cationic L-Lys and hydrophobic L-Leu/L-Ala residues, and Stripe exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria. Gramicidin A (GA), composed of repeating sequences of L- and D-amino acids, has a unique β6.3-helix structure and exhibits broad antimicrobial activity. Inspired by the structural properties and antimicrobial activities of LD-alternating peptides such as GA, in this study, we designed Stripe derivatives with LD-alternating sequences. We found that simply alternating L- and D-amino acids in the Stripe sequence to give StripeLD caused a reduction in antimicrobial activity. In contrast, AltStripeLD, with cationic and hydrophobic amino acids rearranged to yield an amphipathic distribution when the peptide adopts a β6.3-helix, displayed higher antimicrobial activity than AltStripe. These results suggest that alternating L-/D-cationic and L-/D-hydrophobic amino acids in accordance with the helical structure of an AMP may be a useful way to improve antimicrobial activity and develop new AMP drugs.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00465/figure/72_c23-00465.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139659095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Structure–Activity Relationship Study of SNAIL1 Peptides as Inhibitors of Lysine-Specific Demethylase 1 作为赖氨酸特异性去甲基化酶 1 抑制剂的 SNAIL1 肽的结构-活性关系研究

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00671

Yuri Takada, Kyohei Adachi, Yuka Fujinaga, Yasunobu Yamashita, Yukihiro Itoh, Takayoshi Suzuki

{"title":"A Structure–Activity Relationship Study of SNAIL1 Peptides as Inhibitors of Lysine-Specific Demethylase 1","authors":"Yuri Takada, Kyohei Adachi, Yuka Fujinaga, Yasunobu Yamashita, Yukihiro Itoh, Takayoshi Suzuki","doi":"10.1248/cpb.c23-00671","DOIUrl":"https://doi.org/10.1248/cpb.c23-00671","url":null,"abstract":"Peptides have recently garnered attention as middle-molecular-weight drugs with the characteristics of small molecules and macromolecules. Lysine-specific demethylase 1 (LSD1) is a potential therapeutic target for lung cancer, neuroblastoma, and leukemia, and some peptide-based LSD1 inhibitors designed based on the N-terminus of SNAIL1, a member of the SNAIL/SCRATCH family of transcription factors, have been reported. The N-terminus of SNAIL1 peptide acts as a cap of the catalytic site of LSD1, inhibiting interactions with LSD1. However, the structure–activity relationship (SAR) of these inhibitors is not yet fully understood. Therefore, in the present study, we aimed to uncover the SAR and to identify novel SNAIL1 peptide-based LSD1 inhibitors. We synthesized peptide inhibitor candidates based on truncating the N-terminus of SNAIL1 or substituting its amino acid residues. In the truncation study, we found that SNAIL1 1–16 (2), which was composed of 16 residues, strongly inhibited LSD1. Furthermore, we investigated the SAR at residues-3 and -5 from the N-terminus and found that peptides 2j and 2k, in which leucine 5 of the parent peptide is substituted with unnatural amino acids, cyclohexylalanine and norleucine, respectively, strongly inhibited LSD1. This result suggests that the hydrophobic interaction between the inhibitor peptides and LSD1 affects the LSD1-inhibitory activity. We believe that this SAR information provides a basis for the development of more potent LSD1 inhibitors.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00671/figure/72_c23-00671.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139664852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allosteric Hsp70 Modulator YM-1 Induces Degradation of BRD4 异位Hsp70调节剂YM-1诱导BRD4降解

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00543

Yugo Mishima, Shusuke Tomoshige, Shinichi Sato, Minoru Ishikawa

引用次数: 0

Identification of a Histone Deacetylase 8 Inhibitor through Drug Screenings Based on Machine Learning 通过基于机器学习的药物筛选鉴定组蛋白去乙酰化酶 8 抑制剂

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00577

Atika Nurani, Yasunobu Yamashita, Yuuki Taki, Yuri Takada, Yukihiro Itoh, Takayoshi Suzuki

{"title":"Identification of a Histone Deacetylase 8 Inhibitor through Drug Screenings Based on Machine Learning","authors":"Atika Nurani, Yasunobu Yamashita, Yuuki Taki, Yuri Takada, Yukihiro Itoh, Takayoshi Suzuki","doi":"10.1248/cpb.c23-00577","DOIUrl":"https://doi.org/10.1248/cpb.c23-00577","url":null,"abstract":"Histone deacetylase 8 (HDAC8) is a zinc-dependent HDAC that catalyzes the deacetylation of nonhistone proteins. It is involved in cancer development and HDAC8 inhibitors are promising candidates as anticancer agents. However, most reported HDAC8 inhibitors contain a hydroxamic acid moiety, which often causes mutagenicity. Therefore, we used machine learning for drug screening and attempted to identify non-hydroxamic acids as HDAC8 inhibitors. In this study, we established a prediction model based on the random forest (RF) algorithm for screening HDAC8 inhibitors because it exhibited the best predictive accuracy in the training dataset, including data generated by the synthetic minority over-sampling technique (SMOTE). Using the trained RF-SMOTE model, we screened the Osaka University library for compounds and selected 50 virtual hits. However, the 50 hits in the first screening did not show HDAC8-inhibitory activity. In the second screening, using the RF-SMOTE model, which was established by retraining the dataset including 50 inactive compounds, we identified non-hydroxamic acid 12 as an HDAC8 inhibitor with an IC50 of 842 nM. Interestingly, its IC50 values for HDAC1 and HDAC3-inhibitory activity were 38 and 12 µM, respectively, showing that compound 12 has high HDAC8 selectivity. Using machine learning, we expanded the chemical space for HDAC8 inhibitors and identified non-hydroxamic acid 12 as a novel HDAC8 selective inhibitor.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00577/figure/72_c23-00577.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products 医药产品中 N-亚硝胺形成途径的硅学预测

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00550

Genichiro Tsuji, Takashi Kurohara, Takuji Shoda, Hidetomo Yokoo, Takahito Ito, Sayaka Masada, Nahoko Uchiyama, Eiichi Yamamoto, Yosuke Demizu

{"title":"In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products","authors":"Genichiro Tsuji, Takashi Kurohara, Takuji Shoda, Hidetomo Yokoo, Takahito Ito, Sayaka Masada, Nahoko Uchiyama, Eiichi Yamamoto, Yosuke Demizu","doi":"10.1248/cpb.c23-00550","DOIUrl":"https://doi.org/10.1248/cpb.c23-00550","url":null,"abstract":"The recent discovery of N-nitrosodimethylamine (NDMA), a mutagenic N-nitrosamine, in pharmaceuticals has adversely impacted the global supply of relevant pharmaceutical products. Contamination by N-nitrosamines diverts resources and time from research and development or pharmaceutical production, representing a bottleneck in drug development. Therefore, predicting the risk of N-nitrosamine contamination is an important step in preventing pharmaceutical contamination by DNA-reactive impurities for the production of high-quality pharmaceuticals. In this study, we first predicted the degradation pathways and impurities of model pharmaceuticals, namely gliclazide and indapamide, in silico using an expert-knowledge software. Second, we verified the prediction results with a demonstration test, which confirmed that N-nitrosamines formed from the degradation of gliclazide and indapamide in the presence of hydrogen peroxide, especially under alkaline conditions. Furthermore, the pathways by which degradation products formed were determined using ranitidine, a compound previously demonstrated to generate NDMA. The prediction indicated that a ranitidine-related compound served as a potential source of nitroso groups for NDMA formation. In silico software is expected to be useful for developing methods to assess the risk of N-nitrosamine formation from pharmaceuticals.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00550/figure/72_c23-00550.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Near-Infrared Fluorescent Silica Nanoparticles Based on Gold–Silver Alloy Nanoclusters for Clinical Diagnosis 基于金银合金纳米团簇的近红外荧光硅纳米粒子用于临床诊断

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-30 DOI: 10.1248/cpb.c23-00688

Hiroaki Ichimaru, Shigetoshi Kikuchi

{"title":"Near-Infrared Fluorescent Silica Nanoparticles Based on Gold–Silver Alloy Nanoclusters for Clinical Diagnosis","authors":"Hiroaki Ichimaru, Shigetoshi Kikuchi","doi":"10.1248/cpb.c23-00688","DOIUrl":"https://doi.org/10.1248/cpb.c23-00688","url":null,"abstract":"In clinical diagnosis, fluorescent particles are applied to detect analytes in biofluids, such as blood and saliva. However, current fluorescence detection methods have not been optimized to account for the overlapping autofluorescence peaks of biological substances. Gold and silver nanoclusters are known to the novel fluorescent materials and their emission wavelengths depend on cluster size. In this study, we developed fluorescent silica nanoparticles using gold–silver alloy nanoclusters and chitosan (CS) (NH2-SiO2@Au@CS@AuAg) by the layer-by-layer method. Under UV-light irradiation at 365 nm, the emission wavelength of NH2-SiO2@Au@CS@AuAg reached 750 nm in the near-IR region. Scanning electron microscopy images revealed that the shape of NH2-SiO2@Au@CS@AuAg was uniform and spherical. The fluorescence spectrum of horse blood obtained in the presence of NH2-SiO2@Au@CS@AuAg contained a specific fluorescence peak attributed to NH2-SiO2@Au@CS@AuAg, which was distinguishable from the autofluorescence peaks. These results showed that NH2-SiO2@Au@CS@AuAg has advantageous fluorescence properties for clinical diagnostic applications.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/1/72_c23-00688/figure/72_c23-00688.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139586873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, Synthesis, and Biological Evaluation of Water-Soluble Prodrugs of C5-Curcuminoid GO-Y030 Based on Reversible Thia-Michael Reaction 基于可逆 Thia-Michael 反应的 C5-姜黄素 GO-Y030 水溶性原药的设计、合成和生物学评价

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-30 DOI: 10.1248/cpb.c23-00775

Hiroyuki Yamakoshi, Michihiro Fukuda, Hiro Ikeda, Shogo Fujiki, Aki Kohyama, Shota Nagasawa, Hanae Shinozaki, Hiroyuki Shibata, Yoshiharu Iwabuchi

{"title":"Design, Synthesis, and Biological Evaluation of Water-Soluble Prodrugs of C5-Curcuminoid GO-Y030 Based on Reversible Thia-Michael Reaction","authors":"Hiroyuki Yamakoshi, Michihiro Fukuda, Hiro Ikeda, Shogo Fujiki, Aki Kohyama, Shota Nagasawa, Hanae Shinozaki, Hiroyuki Shibata, Yoshiharu Iwabuchi","doi":"10.1248/cpb.c23-00775","DOIUrl":"https://doi.org/10.1248/cpb.c23-00775","url":null,"abstract":"Although curcumin and its analogs exhibit anticancer activity, they are still not used as anticancer drugs because of their water insolubility and extremely poor bioavailability. This study describes the development of water-soluble prodrugs of GO-Y030, a potent antitumor C5-curcuminoid, in an attempt to enhance its bioavailability. These prodrugs release the parent compound via a retro-thia-Michael reaction. To endow sufficient hydrophilicity onto GO-Y030 via a single thia-Michael reaction of an aqueous entity, we used a modified glycoconjugate with a thiol group. The water-solubilizing motif was installed on GO-Y030 by the thia-Michael reaction of propargyl-polyethylene glycol (PEG)-thiol and subsequent click chemistry (CuAAC) reaction with 1-glycosyl azide. Turbidity measurements revealed a significantly improved water solubility of the prodrugs, demonstrating that disaccharide conjugates were completely dissolved in water at 100 µM. Their cytotoxicity was comparable to that of the parent compound GO-Y030, indicating the gradual in situ release of GO-Y030. The release of GO-Y030 from GO-Y199 via the retro-thia-Michael reaction was demonstrated through a degradation study in water. Our retro-thia-Michael reaction-based prodrug system can be used for targeting cancer cells.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/1/72_c23-00775/figure/72_c23-00775.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139586874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and Biological Evaluation of 2-Azolylmethylene-3-(2H)-benzofuranone Derivatives as Potent Monoamine Oxidases Inhibitors 作为强效单胺氧化酶抑制剂的 2-Azolylmethylene-3-(2H)-benzofuranone 衍生物的合成与生物学评价

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-23 DOI: 10.1248/cpb.c23-00763

Koichi Takao, Yuka Kubota, Kota Kurosaki, Hitoshi Kamauchi, Yoshihiro Uesawa, Yoshiaki Sugita

{"title":"Synthesis and Biological Evaluation of 2-Azolylmethylene-3-(2H)-benzofuranone Derivatives as Potent Monoamine Oxidases Inhibitors","authors":"Koichi Takao, Yuka Kubota, Kota Kurosaki, Hitoshi Kamauchi, Yoshihiro Uesawa, Yoshiaki Sugita","doi":"10.1248/cpb.c23-00763","DOIUrl":"https://doi.org/10.1248/cpb.c23-00763","url":null,"abstract":"A series of 2-azolylmethylene-3-(2H)-benzofuranone derivatives, 2-indolylmethylene-3-(2H)-benzofuranone and 2-pyrrolylmethylene-3-(2H)-benzofuranone derivatives, were synthesized, and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Compounds 1b, 3b, 6b, 7b, and 10b showed strong inhibitory activity against MAO-A, and compound 3b showed the highest potency and selectivity, with an IC50 value of 21 nM and a MAO-A selectivity index of 48. Compounds 3c, 4c, 9a, 9c, 10c, 11a, and 11c showed strong inhibitory activity against MAO-B, and compound 4c showed the highest potency and selectivity, with an IC50 value of 16 nM and a MAO-B selectivity index of >1100. Further analysis of these compounds indicated that compound 3b for MAO-A and compound 4c for MAO-B were competitive inhibitors, with Ki values of 10 and 6.1 nM, respectively. Furthermore, computational analyses, such as quantitative structure–activity relationship (QSAR) analysis of the 2-azolylmethylene-3-(2H)-benzofuranone derivatives conducting their pIC50 values with the Molecular Operating Environment (MOE) and Mordred, and molecular docking analysis using MOE-Dock supported that the 2-azolylmethylene-3-(2H)-benzofuranone derivatives are a privileged scaffold for the design and development of novel MAO inhibitors.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/1/72_c23-00763/figure/72_c23-00763.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139518003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Derivation of the Extended Kawakita Equation for Estimating the Yield State of Powder in Die 推导用于估算模具中粉末屈服状态的扩展川北方程

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-18 DOI: 10.1248/cpb.c23-00721

Tsubasa Sato, Naoto Morita, Etsuo Yonemochi, Kozo Takayama

{"title":"Derivation of the Extended Kawakita Equation for Estimating the Yield State of Powder in Die","authors":"Tsubasa Sato, Naoto Morita, Etsuo Yonemochi, Kozo Takayama","doi":"10.1248/cpb.c23-00721","DOIUrl":"https://doi.org/10.1248/cpb.c23-00721","url":null,"abstract":"For powder compaction, the Kawakita equation has been used to estimate the powder behavior inside the die. The compression pressure exerted on powders is not homogeneous because of the friction on the die wall. However, the yield pressure and porosity estimated using the Kawakita equation are defined based on the assumption that homogeneous voids and compression pressure are distributed throughout the powder bed. In this study, an extended Kawakita equation was derived by considering the variation in the compression pressure as it corresponds to the distance from the loading punch surface. The yield time section estimated from the extended Kawakita equation was wider than that which was estimated via the classical equation. This result is consistent with the assumptions used to derive the extended Kawakita equation. Furthermore, a comparison of the porosity changes before and after the yield pressure was applied indicate that the direct cause of the yield is the spatial constraints of the powder particles. Equivalent stresses were defined to clarify the critical factor that constitutes the extended Kawakita equation. As a result, “taking into account the die wall friction” was considered to be the critical factor in the extended Kawakita equation. As these findings were theoretically determined by the extended Kawakita equation, a useful model was derived for a better understanding of powder compaction in die.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/1/72_c23-00721/figure/72_c23-00721.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139480925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0