Chemical & pharmaceutical bulletin最新文献_第2页

Design, Synthesis, and Characterization of 1-(Anthracen-9-ylmethyl)-1,5,9-triazacyclododecane (Ant-[12]aneN3) and Its DNA Photocleavage Activity.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00705

Yoshimi Ichimaru, Koichi Kato, Yoshihiro Yamaguchi, Takayuki Sakamoto, Wanchun Jin, Masaaki Kurihara, Mikako Fujita, Masami Otsuka, Hiromasa Kurosaki

{"title":"Design, Synthesis, and Characterization of 1-(Anthracen-9-ylmethyl)-1,5,9-triazacyclododecane (Ant-[12]aneN3) and Its DNA Photocleavage Activity.","authors":"Yoshimi Ichimaru, Koichi Kato, Yoshihiro Yamaguchi, Takayuki Sakamoto, Wanchun Jin, Masaaki Kurihara, Mikako Fujita, Masami Otsuka, Hiromasa Kurosaki","doi":"10.1248/cpb.c24-00705","DOIUrl":"10.1248/cpb.c24-00705","url":null,"abstract":"Here, a DNA cleavage reagent (1-(anthracen-9-ylmethyl)-1,5,9-triazacyclododecane = Ant-[12]aneN3) was designed and synthesized, and its DNA photocleavage activity under UV irradiation at λ = 365 nm was evaluated. Ant-[12]aneN3 is a molecule containing anthracene as the photosensitizer and [12]aneN3 ( = 1,5,9-triazacyclododecane) as the DNA-interacting component. The cyclic polyamine [12]aneN3 could coordinate with zinc ions (ZnII) and affect DNA cleavage activity. Therefore, when Ant-[12]aneN3 reacted with Zn(NO3)‧6H2O, the product was not a ZnII complex but an N-protonated form of Ant-[12]aneN3. In DNA cleavage experiments with the pUC19 plasmid, Ant-[12]aneN3 also showed DNA photocleavage activity in a ZnII-independent manner. That is, [12]aneN3 enhances the DNA photocleavage activity of anthracene in a ZnII-independent manner, unlike bpa (bis(2-picolyl)amine), which was previously reported to enhance DNA cleavage activity by chelating ZnII. Under physiological conditions, the nitrogen atoms of [12]aneN3 appear protonated without the addition of ZnII salts and showed an affinity for the negatively charged DNA. The results of this study may facilitate the design of effective DNA cleavage reagents.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"103-107"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432554","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

Structure-Signal Relationships of the δ-Opioid-Receptor (DOR)-Selective Agonist KNT-127-Part I: Impact of the Morphinan Skeleton on the G-Protein-Biased DOR Agonism.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00012

Keita Kajino, Tomoya Sugai, Ryoji Kise, Riko Suzuki, Akihisa Tokuda, Yuki Sekiya, Tomoya Kakumoto, Risako Katamoto, Noriki Kutsumura, Yasuyuki Nagumo, Asuka Inoue, Tsuyoshi Saitoh

{"title":"Structure-Signal Relationships of the δ-Opioid-Receptor (DOR)-Selective Agonist KNT-127-Part I: Impact of the Morphinan Skeleton on the G-Protein-Biased DOR Agonism.","authors":"Keita Kajino, Tomoya Sugai, Ryoji Kise, Riko Suzuki, Akihisa Tokuda, Yuki Sekiya, Tomoya Kakumoto, Risako Katamoto, Noriki Kutsumura, Yasuyuki Nagumo, Asuka Inoue, Tsuyoshi Saitoh","doi":"10.1248/cpb.c25-00012","DOIUrl":"https://doi.org/10.1248/cpb.c25-00012","url":null,"abstract":"The δ-opioid receptor (DOR) is a promising target for developing novel analgesics due to its lower risk of causing side effects compared to the μ-opioid receptor (MOR), which is commonly associated with dependence, respiratory depression, and other adverse effects. KNT-127, a DOR-selective agonist with a morphinan skeleton, offers analgesic and antidepressant benefits without inducing convulsions at therapeutic doses, unlike the conventional DOR agonist SNC80. While previous studies have suggested that KNT-127 exhibits reduced β-arrestin recruitment, a signaling pathway implicated in adverse opioid effects, the ligand structural basis for this biased signaling remains unclear. In this study, we explored the structure-signal relationships of KNT-127, focusing on its quinoline moiety, which is known to serve as an address domain responsible for DOR selectivity. Modifying the quinoline moiety by removing the aromatic rings reduced DOR selectivity and potency in relation to G-protein activation while diminishing both the potency and efficacy of β-arrestin recruitment. These results suggest that the morphinan skeleton is critical for reduced β-arrestin recruitment, while the quinoline moiety differentially modulates G-protein activation and β-arrestin recruitment. Together, our study expands the message-address concept, previously limited to receptor selectivity, by providing structural insights into the G-protein-biased agonism of DOR agonists, thereby guiding the design of safer DOR-targeting therapeutics.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"246-256"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750362","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

Concise and Highly Stereoselective Synthesis of β,β-Disubstituted α,β-Unsaturated Esters.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00751

Minoru Ozeki, Mizuki Tsuda, Serina Yamanouchi, Momoe Yamakawa, Kanako Fukuda, Hirotaka Sasa, Takuya Matsumoto, Aya Niki, Maaya Nobata, Takashi Shigeta, Tetsuya Kajimoto, Kenji Arimitsu, Shinzo Hosoi, Hiroki Iwasaki, Naoto Kojima, Ikuo Kawasaki

引用次数: 0

Effects of Shape on the Disintegration Time and Friability of Sucroferric Oxyhydroxide-Containing Mini-Tablets.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00675

Hiroaki Omori, Homare Kurashima, Nobuyuki Isshiki, Yasuharu Kashiwagura, Shinya Uchida

{"title":"Effects of Shape on the Disintegration Time and Friability of Sucroferric Oxyhydroxide-Containing Mini-Tablets.","authors":"Hiroaki Omori, Homare Kurashima, Nobuyuki Isshiki, Yasuharu Kashiwagura, Shinya Uchida","doi":"10.1248/cpb.c24-00675","DOIUrl":"https://doi.org/10.1248/cpb.c24-00675","url":null,"abstract":"Sucroferric oxyhydroxide is a phosphate binder for the treatment of hyperphosphatemia in patients with chronic kidney disease undergoing dialysis. This study aimed to determine the effects of tablet size, shape, and tensile strength on disintegration time and friability of sucroferric oxyhydroxide-containing mini-tablets. A linear relationship between the disintegration time and tensile strength was observed across all mini-tablets, except for those with smaller tablets (diameters: <1.8 mm). However, the relationship between friability and tensile strength was not significantly correlated under linear or exponential approximations. Explaining friability solely based on tensile strength was challenging, indicating the role of tablet shape. To visualize the effects of mini-tablet shapes and tensile strength on their disintegration time and friability, response aspects were analyzed. The response surface analysis revealed that the disintegration time was not affected by the tablet shape. The friability of the mini-tablets with a cup depth/diameter of 0.209 was lower (<0.2) than that of tablets with other cup depth/diameter across all tested ranges of tensile strength (1-6). A cup depth/diameter of 0.2 was identified as optimal for minimizing the friability of mini-tablets and can be implemented in commercial production without issues. In conclusion, tablet shape should be carefully considered during the development of mini-tablets to ensure low friability.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"257-263"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751401","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

Preparation of a Stable Indomethacin Supersaturated Solution Using Hydrophobically Modified Hydroxypropylmethylcellulose and α-Cyclodextrin.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00748

Hiroki Akahoshi, Fumitoshi Hirayama, Kenjirou Higashi, Daisuke Iohara

{"title":"Preparation of a Stable Indomethacin Supersaturated Solution Using Hydrophobically Modified Hydroxypropylmethylcellulose and α-Cyclodextrin.","authors":"Hiroki Akahoshi, Fumitoshi Hirayama, Kenjirou Higashi, Daisuke Iohara","doi":"10.1248/cpb.c24-00748","DOIUrl":"10.1248/cpb.c24-00748","url":null,"abstract":"In the present study, the stability of a supersaturated solution of indomethacin (IM) was evaluated in hydrophobically modified hydroxypropylmethylcellulose (HM-HPMC) solutions, with and without parent cyclodextrins (CDs). A highly supersaturated state of IM was maintained in the HM-HPMC solution and was further stabilized by the addition of α-CD and β-CD. Notably, the highest level of supersaturation was achieved in HM-HPMC/α-CD solution, which maintained a high concentration of IM for up to 120 h. IM concentrations in these solutions exceeded the amorphous solubility, indicating that phase separation had occurred. To explore this phase separation, Nile Red, a fluorescent probe sensitive to hydrophobic environments, was added to the supersaturated solutions. A higher fluorescence intensity was observed in the HM-HPMC/α-CD solution compared with the HM-HPMC solution, indicating a significant formation of colloidal amorphous aggregates in the supersaturated solution. Cryogenic transmission electron microscopy (Cryo TEM) analysis confirmed the presence of these aggregates, which appeared irregularly shaped. These findings suggest that the combination of HM-HPMC and α-CD effectively stabilized the colloidal amorphous aggregates in the IM supersaturated solution. The addition of α-CD facilitated the dissociation of HM-HPMC into smaller particles, increasing the number of hydrophobic stearyl moieties available for interactions with amorphous IM aggregates, thereby enhancing the stability of the supersaturated state. The combination of HM-HPMC and α-CD offers a promising approach to improving the oral bioavailability of drugs with poor water solubility.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 1","pages":"39-45"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022318","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

Toward the Synthesis of Strychnos Alkaloids: Effective Construction of Fused Cyclohexane and Pyrrolidine Portion of the Strychnos Skeleton via Domino Intermolecular and Intramolecular S_N2 Cyclization.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00783

Tadahiro Hosoda, Tomohiro Tsutsumi, Ichiro Hayakawa

引用次数: 0

Hyaluronan Tetrasaccharides Penetrate into the Skin by Passive Diffusion and Contribute to Skin Health.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c23-00909

Yutaka Takagi, Madoka Kage

引用次数: 0

Bioinspired Total Synthesis of Polycyclic Natural Products.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00843

Hayato Ishikawa

引用次数: 0

Two New Halimanes with a γ-Lactone from Croton argyratus.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00734

Kanami Watanabe, Yohei Saito, Shuichi Fukuyoshi, Katsunori Miyake, David J Newman, Barry R O'Keefe, Kuo-Hsiung Lee, Kyoko Nakagawa-Goto

引用次数: 0

Highly Precise Anomaly Detection Using Multivariate Statistical Process Control with Appropriate Scaling of Input Variables in Pharmaceutical Continuous Manufacturing.

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00652

Takuya Oishi, Takuya Nagato, Chikara Tsujikawa, Takuya Minamiguchi, Sanghong Kim

{"title":"Highly Precise Anomaly Detection Using Multivariate Statistical Process Control with Appropriate Scaling of Input Variables in Pharmaceutical Continuous Manufacturing.","authors":"Takuya Oishi, Takuya Nagato, Chikara Tsujikawa, Takuya Minamiguchi, Sanghong Kim","doi":"10.1248/cpb.c24-00652","DOIUrl":"https://doi.org/10.1248/cpb.c24-00652","url":null,"abstract":"Multivariate statistical process control (MSPC) has attracted considerable attention as a monitoring method for pharmaceutical continuous manufacturing. However, there are few examples of its application in pharmaceutical manufacturing, and previous studies have shown high false-positive rates. One of the reasons is the use of inappropriate scaling factors. In pharmaceutical processes, the number of experiments for MSPC modeling tends to be small because the active pharmaceutical ingredients are expensive. Subsequently, the standard deviation, a common scaling factor for some variables, becomes too small, and the model may become sensitive to small variations. In this study, we have proposed methods for determining the appropriate scaling factors. These methods were applied to granulation and drying processes in pharmaceutical continuous manufacturing. The MSPC model can detect changes in the process parameters and raw materials used during continuous wet granulation and fluidized bed drying using the proposed scaling method.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"234-245"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750108","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