Chemical & pharmaceutical bulletin最新文献_第10页

In Vitro Study on Combined Effect of Drugs for Hyperphosphatemia on Phosphorus Adsorption Capacity. 治疗高磷血症的药物对磷吸附能力的联合影响体外研究

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00434

Kaito Yamashiro, Kazuma Kimata, Fumihiko Ogata, Naohito Kawasaki

{"title":"In Vitro Study on Combined Effect of Drugs for Hyperphosphatemia on Phosphorus Adsorption Capacity.","authors":"Kaito Yamashiro, Kazuma Kimata, Fumihiko Ogata, Naohito Kawasaki","doi":"10.1248/cpb.c24-00434","DOIUrl":"https://doi.org/10.1248/cpb.c24-00434","url":null,"abstract":"Phosphorus binders are often used in combination to produce synergistic effects. However, the synergistic effect may be affected by the change in pH or concomitant drugs. Nonetheless, the data on the adsorption capacities of these binders when used in combination with other binders are limited. In this study, we evaluated the adsorption capacity of phosphorus binders when used in combination. Precipitated calcium carbonate (CC), ferric citrate hydrate (FC), lanthanum carbonate hydrate (LC), and sucroferric oxyhydroxide (SO) were used as phosphorus binders. SO showed high adsorption capacity in the 1st and 2nd fluid, and the adsorption capacity of SO in combination with other binders was stable. In contrast, the adsorption capacities of CC + FC and FC + LC decreased in the 1st and 2nd fluid compared with that when used alone because of the release of citrate ions that chelate calcium or lanthanum ions. These results suggest that SO is less affected by interactions with other phosphorus binders and changes in pH and may be suitable for patients receiving concomitant drugs.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 10","pages":"932-935"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543939","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

Substitution Effects of Alkene Dipeptide Isosteres on Adjacent Peptide Bond Rotation. 烯二肽异构体对相邻肽键旋转的取代效应。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00254

Chihiro Iio, Kohei Sato, Nobuyuki Mase, Tetsuo Narumi

引用次数: 0

Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case. 新型药物早期临床阶段干法制粒研究的系统 DOE 方法：一个工业案例

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00801

Weiqi Chen, Xiaolei Wang, Hengli Yuan, Qixuan Guan, Chun Wang, Zhiying Dong, Shicheng Zhang, Jianping Yao, Jinyang Shen

{"title":"Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.","authors":"Weiqi Chen, Xiaolei Wang, Hengli Yuan, Qixuan Guan, Chun Wang, Zhiying Dong, Shicheng Zhang, Jianping Yao, Jinyang Shen","doi":"10.1248/cpb.c23-00801","DOIUrl":"https://doi.org/10.1248/cpb.c23-00801","url":null,"abstract":"In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 6","pages":"584-595"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466470","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

Evaluating a Retro-Inverso Type Inhibitor of HTLV-1 Protease as a Competitive Inhibitor. 评估作为竞争性抑制剂的 HTLV-1 蛋白酶逆转录抑制剂。

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00879

Chiyuki Awahara, Daiki Oku, Kazuya Kobayashi, Yasunao Hattori

引用次数: 0

Facile Synthesis of 1,2-Disubstituted Benzimidazoles as Potent Cytotoxic Agents. 作为强效细胞毒性药物的 1,2-二取代苯并咪唑的简便合成。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00570

Hue Thi Buu Bui, Zin Paing Htoo, Quang Vinh Hong, Hieu Trong Le, De Quang Tran, Saw Yu Yu Hnin, Kiep Minh Do, Hiroyuki Morita

{"title":"Facile Synthesis of 1,2-Disubstituted Benzimidazoles as Potent Cytotoxic Agents.","authors":"Hue Thi Buu Bui, Zin Paing Htoo, Quang Vinh Hong, Hieu Trong Le, De Quang Tran, Saw Yu Yu Hnin, Kiep Minh Do, Hiroyuki Morita","doi":"10.1248/cpb.c24-00570","DOIUrl":"https://doi.org/10.1248/cpb.c24-00570","url":null,"abstract":"Benzimidazoles have a broad spectrum of biological and pharmacological properties, including anticancer activity. This study reports the facile synthesis and cytotoxic evaluation of twenty-eight 1,2-disubstituted benzimidazoles (6a-β), based on condensation reactions between N-benzyl o-phenylenediamine and benzylamine. The reactions were solvent-free, with the use of Na2S2O5 as an inexpensive and environmentally friendly oxidizing agent, and progressed rapidly. Cytotoxicity assessments using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed against the A549, HeLa, and MCF-7 cell lines for all synthesized compounds (6a-β). Among them, 6j, 6k, 6l, and 6n displayed good activities against the A549 and MCF-7 cell lines. These compounds possessed IC50 values ranging from 2.55 to 4.50 µM, corresponding to 1.4-fold to 2.4-fold stronger potencies than that of the positive control 5-fluorouracil (5-FU) (IC50 = 6.08 µM) against MCF-7 cells, while 6k (IC50 = 3.22 µM) was consistent with 5-FU on the A549 cell line (IC50 = 3.77 µM). Structure-activity relationship analyses revealed the 3-pyridinyl moiety at C-2 and the CH3, OCH3, or 1,3-dioxolyl groups on the benzene ring at the N-1 position of the benzimidazole heterocycle as key structural features effectuating the observed cytotoxicities.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 11","pages":"944-949"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590142","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

Errata for Chemical and Pharmaceutical Bulletin. 化学与制药公报》勘误表。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-e7204

引用次数: 0

Anti-amyloid-β Antibodies and Anti-tau Therapies for Alzheimer's Disease: Recent Advances and Perspectives. 治疗阿尔茨海默病的抗淀粉样蛋白-β抗体和抗tau疗法：最新进展与展望》。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-00069

Naoyuki Suzuki, Takuya Hatta, Mana Ito, Ken-Ichi Kusakabe

{"title":"Anti-amyloid-β Antibodies and Anti-tau Therapies for Alzheimer's Disease: Recent Advances and Perspectives.","authors":"Naoyuki Suzuki, Takuya Hatta, Mana Ito, Ken-Ichi Kusakabe","doi":"10.1248/cpb.c24-00069","DOIUrl":"https://doi.org/10.1248/cpb.c24-00069","url":null,"abstract":"Amyloid-β (Aβ) plaques and neurofibrillary tangles containing phosphorylated tau protein are major hallmarks of Alzheimer's disease (AD). Drug discovery efforts to target Aβ and tau have been the primary focus for several decades. Recently, substantial breakthroughs have been achieved in the clinical development of Aβ antibodies; aducanumab was approved under conditional accelerated pathway by Food and Drug Administration (FDA) in the U.S. as the first disease-modifying agent for treating AD, and lecanemab has been granted traditional full approved in the U.S. and Japan. In addition, donanemab met the primary endpoint in a phase 3 study. On the other hand, tau-targeting therapies have failed to show clinical benefit although that increased tau levels show a strong correlation with cognitive impairment relative to Aβ depositions. Currently, tau immunotherapies, such as anti-tau antibodies and tau vaccines, have shown functional benefits in clinical trials. Also, clinical trials for combination therapy of Aβ and tau antibodies to see their potential are being investigated. In this review, we provide updates on the results of clinical trials of anti-Aβ antibodies and anti-tau therapeutics and suggest future directions for these therapeutics.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 7","pages":"602-609"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466471","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

Foreword. 前言

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c24-ctf7207

Ken-Ichi Kusakabe

引用次数: 0

Epigenetic Inhibitors as Alzheimer's Disease Therapeutic Agents. 表观遗传抑制剂作为阿尔茨海默病治疗药物。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00027

Yasunobu Yamashita, Yukihiro Itoh, Yuri Takada, Takayoshi Suzuki

{"title":"Epigenetic Inhibitors as Alzheimer's Disease Therapeutic Agents.","authors":"Yasunobu Yamashita, Yukihiro Itoh, Yuri Takada, Takayoshi Suzuki","doi":"10.1248/cpb.c23-00027","DOIUrl":"https://doi.org/10.1248/cpb.c23-00027","url":null,"abstract":"Alzheimer's disease (AD) is the leading cause of senile dementia, and the rapid increase in the frequency of AD cases has been attributed to population aging. However, current drugs have difficulty adequately suppressing symptoms and there is still a medical need for symptomatic agents. On the other hand, it has recently become clear that epigenetic dysfunctions are deeply involved in the development of cognitive impairments. Therefore, epigenetics-related proteins have attracted much attention as drug targets for AD. Early-developed epigenetic inhibitors were inappropriate for AD treatment because of their limited potential for oral administration, blood-brain barrier penetration, high target selectivity, and sufficient dose-limiting toxicity which are essential properties for small molecule drugs targeting chronic neurodegenerative diseases such as AD. In recent years, drug discovery studies have been actively performed to overcome such problems and several novel inhibitors targeting the epigenetics-related proteins are of interest as promising AD therapeutic agents. Here, we review the small molecule inhibitors of histone deacetylase (HDAC), lysine-specific demethylase 1 (LSD1) or bromodomains and extra-terminal domain (BET) protein, that enable memory function improvement in AD model mice.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 7","pages":"630-637"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466473","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

Neuroimmune Dysfunction in Alzheimer's Disease and Other Forms of Dementia. 阿尔茨海默病和其他形式痴呆症的神经免疫功能障碍

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/cpb.c23-00464

Takuya Yamane, Takeshi Yoshioka, Yusuke Shimo

{"title":"Neuroimmune Dysfunction in Alzheimer's Disease and Other Forms of Dementia.","authors":"Takuya Yamane, Takeshi Yoshioka, Yusuke Shimo","doi":"10.1248/cpb.c23-00464","DOIUrl":"https://doi.org/10.1248/cpb.c23-00464","url":null,"abstract":"Alzheimer's disease (AD) is a common form of dementia. Although the causal mechanisms of AD are not fully understood, intracerebral accumulation of amyloid beta (Aβ) and tau aggregates seems to play an important role in disease development. Therefore, numerous experimental and clinical studies targeting the Aβ and tau proteins have been performed. However, these treatments have not achieved good clinical results. Additionally, recent findings have indicated that immune abnormalities contribute to the pathogenesis of AD. Several immune- and microglia-related genes have been identified as putative causative genes for the disease. Microglia, which are resident immune cells in the central nervous system (CNS), are key players that maintain brain homeostasis by communicating with other cells, such as astrocytes and immune cells, in or around the CNS. Furthermore, dysfunction of microglia and the immune system of the CNS could lead to chronic neuroinflammation and impairment of protective neuroimmune responses, which have been associated with the pathogenesis of AD and other forms of dementia. In this review, we assemble information regarding genetic evidence, imaging and biofluid biomarkers, and the pathophysiology of AD, especially highlighting bilateral (protective or detrimental) microglial functions, thus connecting neuroimmune dysfunction and AD. We also introduce candidate drugs to target neuroimmune dysfunction in AD. Finally, we discuss future therapeutic precision medicine approaches for AD, which could be achieved by identifying and targeting signals critical for AD pathogenesis through analyses of interactions between genetic risk factors, as well as identifying and modulating disease-relevant immune cell populations.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 7","pages":"618-629"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466476","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