Medicinal Chemistry Research最新文献

{"title":"SAR exploration for 4-aminotetrahydroquinazolines with adamantyl moiety against orthoflaviviruses","authors":"Sergey V. Kositov,&nbsp;Evgeny V. Khvatov,&nbsp;Victoria I. Uvarova,&nbsp;Kseniya N. Sedenkova,&nbsp;Alexander S. Goryashchenko,&nbsp;Maria K. Kaleda,&nbsp;Aleksandra V. Peisikova,&nbsp;Yuri K. Grishin,&nbsp;Boris P. Gladkikh,&nbsp;Gennady M. Butov,&nbsp;Dmitry I. Osolodkin,&nbsp;Aydar A. Ishmukhametov,&nbsp;Elena B. Averina","doi":"10.1007/s00044-026-03539-0","DOIUrl":"10.1007/s00044-026-03539-0","url":null,"abstract":"<div><p>4-Aminotetrahydroquinazoline <i>N</i>-oxides form a prominent chemotype of orthoflavivirus reproduction inhibitors, attractive for the search of lead compounds for development as direct-action antiviral agents. Here we explored the relationship between the structure and antiviral activity within an extended series of adamantyl-containing 4-aminotetrahydroquinazolines, synthesized via S_NAr reactions of 4-chlorotetrahydroquinazolines with adamantyl-containing amines. Most of the obtained compounds inhibited the reproduction of tick-borne encephalitis, yellow fever, and West Nile viruses in phenotypic assays with micromolar EC₅₀s. The most favorable substituents at 4-amino group were 2-adamant-(1/2)-ylethyls, while the position 2 of heterocyclic core served as a toxicity switch, 2-chlorotetrahydroquinazolines being much less toxic than other analogues. Time-of-addition experiments for hit compounds against West Nile virus revealed a possibility for multi-factorial mechanism of action in the 4-aminotetrahydroquinazoline series.</p><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 5","pages":"919 - 931"},"PeriodicalIF":3.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148009975","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}

{"title":"From empirical screening to lipid trolling: the evolution of extrahelical allosteric modulators of A1 and A3 adenosine receptors","authors":"Matteo Pavan,&nbsp;Siva Hariprasad Kurma,&nbsp;Paola Oliva,&nbsp;David P. Broughton,&nbsp;Zhan-Guo Gao,&nbsp;John A. Auchampach,&nbsp;Kenneth A. Jacobson","doi":"10.1007/s00044-026-03534-5","DOIUrl":"10.1007/s00044-026-03534-5","url":null,"abstract":"<div><p>An early GPCR positive allosteric modulator (PAM) was the 2-amino-3-benzoylthiophene derivative PD81,723, which enhances G_i-coupled A₁ adenosine receptor (AR) agonist effects. Cryo-EM studies located its extrahelical binding site on TMs 5 and 6, and extensive empirical SAR is consistent with the experimental A₁AR structure. At the anti-inflammatory A₃AR, a series of 1<i>H</i>-imidazo[4,5-<i>c</i>]quinolin-4-amine PAMs, originally derived from an A₁AR antagonist scaffold, was recently found, using mutagenesis and molecular modeling, to bind at an extrahelical, lipid-exposed site on the receptor. The <i>N</i>4 and C2 positions on the scaffold were modified with substituted phenyl and cycloalkyl/branched alkyl groups, respectively, as in the prototypical PAM LUF6000. Before the structural binding hypothesis, extensive synthetic optimization failed to introduce hydrophilic groups needed for aqueous compatibility. Eventually, secondary anchoring of these A₃AR PAMs within the phospholipid bilayer (lipid trolling) succeeded in improving the pharmacological profile, based on the attraction of appended terminal cationic chains on the PAM with anionic phospholipid head groups. Molecular dynamics (MD) simulation has predicted a rearrangement of anionic lipids around H8 when long-amino chain PAMs bind, and an upward movement of H8 that is reported to be associated with Class A GPCR activation. <i>N</i>1 alkylation with benzyl groups removed residual A₃AR antagonism and produced substantial enhancement of agonist potency as well as E_max. Both A₁AR and A₃AR PAMs can activate partially in the absence of orthosteric agonist. Thus, at both receptors, potent PAMs have been discovered and optimized for selective enhancement of endogenous adenosine and potentially for treatment of conditions such as chronic pain. Collectively, extrahelical, lipid-exposed pockets are druggable allosteric sites in Class A GPCRs and amenable to deliberate engagement of the membrane environment to optimize receptor modulation. The evolution from empirical screening to structure-guided and membrane-aware design provides a generalizable framework for targeting signaling across the GPCR superfamily beyond ARs.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 10","pages":"1821 - 1838"},"PeriodicalIF":3.5,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03534-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inactivation of ornithine aminotransferase by (1R,4S)-4-Amino-3-(trifluoromethyl)cyclopent-2-ene-1-carboxylic acid via a stable quinonoid intermediate","authors":"Koon Mook Kang,&nbsp;Abigail L. Vargas,&nbsp;Wei Zhu,&nbsp;Inna Sokolenko,&nbsp;Dali Liu,&nbsp;Richard B. Silverman","doi":"10.1007/s00044-026-03538-1","DOIUrl":"10.1007/s00044-026-03538-1","url":null,"abstract":"<div><p>Ornithine aminotransferase (OAT), a pyridoxal 5’-phosphate (PLP)-dependent enzyme, is a key contributor to glutamine supply in cancer cells, suggesting its therapeutic potential for hepatocellular carcinoma (HCC), the most common form of liver cancer. To identify an initial set of OAT inactivators, we have tested inactivators of γ-aminobutyric acid aminotransferase (GABA-AT), a homologous PLP-dependent enzyme, with human OAT (<i>h</i>OAT) and identified several co-inactivators. Among the active molecules, (1<i>R</i>,4<i>S</i>)-4-amino-3-(trifluoromethyl)cyclopent-2-ene-1-carboxylic acid (<b>2</b>) has not been thoroughly investigated for its time-dependent kinetics and mechanistic pathways with OAT. In this study, we evaluated the time-dependent inactivation of <i>h</i>OAT by <b>2</b> and investigated the underlying mechanism, primarily based on X-ray crystallography. The results demonstrated that <b>2</b> acts as a time-dependent OAT inactivator with an inactivation efficiency (<i>k</i>_inact/<i>K</i>_I = 5.1 min⁻¹mM⁻¹) approximately 30-fold higher than that for GABA-AT (<i>k</i>_inact/<i>K</i>_I = 0.17 min⁻¹mM⁻¹) and, notably, revealed an inactivation pathway that proceeds via a stable quinonoid intermediate, as evidenced by the UV-Vis spectroscopy.</p><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 4","pages":"792 - 803"},"PeriodicalIF":3.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03538-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Siderophore–Porphyrin conjugates for bacteria-selective antimicrobial photodynamic therapy","authors":"Jinyoung Oh,&nbsp;Seunghyun Choi,&nbsp;Woojin Yang,&nbsp;Jieun Choi,&nbsp;Jiwon Seo","doi":"10.1007/s00044-026-03537-2","DOIUrl":"10.1007/s00044-026-03537-2","url":null,"abstract":"<div><p>Targeted delivery of photosensitizers represents a key strategy for improving the selectivity and efficacy of antimicrobial photodynamic therapy (aPDT). Herein, we describe the synthesis and biological evaluation of siderophore-conjugated photosensitizers designed to exploit bacterial iron acquisition pathways. Four distinct photosensitizers—neutral porphyrin (TPP), cationic porphyrin (TMPyP), metalloporphyrin (PdTMPyP), and chlorin (Ce6)—were covalently linked to deferoxamine B (DFO), a clinically approved hydroxamate siderophore. The resulting conjugates retained their intrinsic photophysical properties while exhibiting iron-dependent antimicrobial activity against siderophore-utilizing pathogens. TMPyP-DFO (<b>3</b>) was determined as the best compound, demonstrating potent antimicrobial photodynamic activity against <i>Staphylococcus aureus</i> and <i>Acinetobacter baumannii</i> under iron-deficient conditions (MIC₅₀ = 6.3–12.5 µM) with low mammalian cytotoxicity (LC₅₀ = 146.6 µM). Neutral porphyrin- and chlorin-siderophore conjugates (<b>1</b> and <b>2</b>, respectively) demonstrated either poor activity or lack of selectivity. These findings validate the ‘Trojan horse’ delivery strategy—achieved through the conjugation of cationic porphyrins with siderophores—as a promising strategy for enhancing bacterial selectivity in aPDT.</p><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 4","pages":"804 - 813"},"PeriodicalIF":3.1,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754472","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}

{"title":"Design, synthesis, biological evaluation, and computational studies of chalcone scaffolds as cholinesterase inhibitors","authors":"Xue-Wei Zhou,&nbsp;Yi-Xuan Wang,&nbsp;Wen-Rong Du,&nbsp;Chao-Yue Zhang,&nbsp;Shi-Hao Qin,&nbsp;Zheng-Yue Ma","doi":"10.1007/s00044-026-03536-3","DOIUrl":"10.1007/s00044-026-03536-3","url":null,"abstract":"<div><p>A series of chalcone derivatives (<b>8a-8v</b>) was designed and synthesized, and their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The inhibitory activities of AChE and BuChE were measured using the Ellman method. The results showed that most compounds exhibited moderate to weak inhibitory activity against both AChE and BuChE. Among them, compound <b>8g</b> displayed potent AChE inhibitory activity with an IC₅₀ of 2.59 μM and moderate BuChE inhibitory activity with an IC₅₀ of 8.89 μM. The inhibitory effects of compound <b>8g</b> on both enzymes surpassed those of the positive control, galantamine. Next, the antioxidant activity of these compounds was assessed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay, revealing that compound <b>8j</b> had the strongest antioxidant activity, with an IC₅₀ of 65.84 μM, while the others showed weak antioxidant activity. Enzyme kinetic studies confirmed that compound <b>8g</b> acts as a mixed-type inhibitor. Molecular docking indicated that compound <b>8g</b> interacts with both the catalytic active site (CAS) and peripheral anion site (PAS) of AChE. Molecular dynamics (MD) simulations verified the stability of the <b>8g</b>-AChE/BuChE complex. Overall, these experimental results suggest that the designed and synthesized cholinesterase inhibitor (ChEI) <b>8g</b> has potential for further development.</p><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 5","pages":"903 - 918"},"PeriodicalIF":3.1,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148008640","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}

{"title":"From METTL3 PROTACs to pyroptosis-coupled design: a medicinal chemistry agenda for next-generation targeted degraders","authors":"M. Vijayasimha","doi":"10.1007/s00044-026-03535-4","DOIUrl":"10.1007/s00044-026-03535-4","url":null,"abstract":"","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 5","pages":"867 - 870"},"PeriodicalIF":3.1,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148008846","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}

{"title":"Synthesis and structure-activity relationship evaluation of hypoglycemic activity of novel borneol and isoborneol containing (hydroxyphenyl)propanoic acids as FFAR1 agonists","authors":"Sergey O. Kuranov,&nbsp;Mikhail V. Larin,&nbsp;Irina D. Levchenko,&nbsp;Yulia V. Meshkova,&nbsp;Mariya K. Marenina,&nbsp;Olga A. Luzina,&nbsp;Mikhail V. Khvostov,&nbsp;Tatiana G. Tolstikova,&nbsp;Nariman F. Salakhutdibov","doi":"10.1007/s00044-026-03532-7","DOIUrl":"10.1007/s00044-026-03532-7","url":null,"abstract":"<div><p>Free Fatty Acid Receptor-1 (FFAR1) agonists are promising candidates for the treatment of type 2 diabetes mellitus due to their glucose-lowering ability. Previously, we have shown that a benzyloxyphenylpropanoic acid derivative <b>QS-619</b> (<b>5d</b>) containing a (−)-borneol residue acts as an effective FFAR1 agonist and exerts a hypoglycemic effect in mice. To establish the initial structure-activity relationships (SAR) for this chemotype, with a particular focus on the critical role of the terpene fragment’s stereochemistry, we synthesized a series of its structural analogues with variations in the configuration of stereocenters and the position of substituents in the aromatic rings. The effect of borneol stereochemistry on hypoglycemic activity was studied. The cytotoxicity of the synthesized compounds was evaluated on HepG2 and HEK293T cell lines. The hypoglycemic activity of these compounds was assessed in an oral glucose tolerance test (OGTT) in mice at doses of 15 mg/kg and 30 mg/kg. The most potent hypoglycemic agent identified was compound <b>5e</b> which bears a (+)-bornyl moiety. It demonstrated a strong effect at both doses, showed no cytotoxicity (CC₅₀ &gt;100 µM), but exhibited acute toxicity at a dose of 1000 mg/kg. Compounds <b>5f</b> and <b>5g</b>, containing (−)- and (+)-isobornyl moieties, respectively, showed a less pronounced hypoglycemic effect compared to the bornyl derivatives <b>5d</b> and <b>5e</b>. The cyclohexyl derivative <b>5h</b> was active only at the 30 mg/kg dose. Furthermore, co-administration of an FFAR1 antagonist was found to suppress the hypoglycemic activity of the studied compounds in the OGTT, supporting an FFAR1-mediated mechanism of action.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 3","pages":"649 - 663"},"PeriodicalIF":3.1,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429374","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}

{"title":"Discovery of quinazoline-based derivatives as novel autophagy inhibitors in pancreatic cancer","authors":"Dongxuan Ni,&nbsp;Man Jin,&nbsp;Hongyuan Zhou,&nbsp;Ruoxi Xue,&nbsp;Fudong Wu,&nbsp;Tongyi Pu,&nbsp;Bin Liang,&nbsp;Ruihan Zhang,&nbsp;Jia Su,&nbsp;Weilie Xiao","doi":"10.1007/s00044-026-03533-6","DOIUrl":"10.1007/s00044-026-03533-6","url":null,"abstract":"<div><p>Pancreatic cancer remains a highly lethal malignancy with limited treatment options. Given the versatile bioactivity of quinazoline derivatives, which are regarded as a promising scaffold for anticancer drug discovery, we designed and synthesized a series of novel quinazoline analogues. Their cytotoxicity was evaluated in three pancreatic cancer cell lines (HPAC, AsPC-1, and MIA PaCa-2), leading to the identification of compound <b>5a</b>, which exhibited potent effects across all tested cell lines. Further investigation of anticancer activity indicated that <b>5a</b> significantly inhibited DNA synthesis, clonogenesis, and migration in MIA PaCa-2 cells. Mechanism study revealed that <b>5a</b> disrupted autophagy, as evidenced by downregulation of Beclin-1 expression and accumulation of LC3B-II and p62, through a mechanism independent of the canonical AMPK-mTOR-ULK1 signaling pathway. This study provides a promising active scaffold for the development of anti-pancreatic cancer agents.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 3","pages":"634 - 648"},"PeriodicalIF":3.1,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429375","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}

{"title":"Volkameria (L.): A comprehensive review of its traditional medicine uses, phytochemistry and pharmacology","authors":"Shreyanshi Kulshreshtha,&nbsp;Bhawana Jangra,&nbsp;Yogita B. Tandalekar,&nbsp;Alok Goyal,&nbsp;Sanjay M. Jachak","doi":"10.1007/s00044-026-03531-8","DOIUrl":"10.1007/s00044-026-03531-8","url":null,"abstract":"<div><p>The genus <i>Volkameria</i>, belonging to the family Lamiaceae, comprises flowering plants with a pantropical distribution and a rich diversity of traditional applications and phytochemical compositions. Currently, 13 species are classified under this genus, which were previously categorized under different genera. This review aims to summarize the most up-to-date botanical descriptions, geographical distributions, ethnobotanical uses, phytochemistry, and pharmacological activities of <i>Volkameria</i> plants. Various databases and search engines, such as PubMed, Science Direct, Google Scholar, Sci-finder, Research Gate, online floras, and other published/unpublished resources, were consulted to compile this article. <i>Volkameria</i> species have been extensively used in traditional medicinal practices across different cultures to treat conditions such as fever, malaria, edema, cough, skin diseases, ulcers, inflammation, and rheumatism. Among the 13 accepted species, only four have been phytochemically investigated, with significant research focused on <i>Volkameria inermis</i>. Nearly 145 phytochemicals belonging to various classes, including flavonoids, diterpenoids, triterpenoids, steroids, and phenolic/lignan/iridoid/megastigmane glycosides, have been isolated and reported. Notably, flavonoids, diterpenoids, and triterpenoids have shown significant biological activities. <i>V. glabra</i>, and <i>V. inermis</i> have been studied for their pharmacological properties, such as antioxidant, anti-inflammatory, antimicrobial (including antibacterial, antiviral, antifungal, antimalarial, neuroprotective, anti-motor tics, insecticidal, and antifeedant effects. However, the remaining species require further investigation. Comprehensive studies, including preclinical and clinical trials, are essential to validate the efficacy and safety of these plants for medicinal use.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 3","pages":"506 - 547"},"PeriodicalIF":3.1,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429367","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}

{"title":"Design, synthesis and insecticidal activities of novel meta-diamide compounds containing ethyl group","authors":"Dong Li,&nbsp;Zhu Xia,&nbsp;Jiyong Liu,&nbsp;Juncheng Xiang,&nbsp;Qiqi Huang,&nbsp;Liang Lv,&nbsp;Hang Gong,&nbsp;Kangming Li","doi":"10.1007/s00044-026-03529-2","DOIUrl":"10.1007/s00044-026-03529-2","url":null,"abstract":"<div><p>To develop structurally novel and efficient insecticides, a series of ethylpyridine-containing meta-diamide derivatives were designed and synthesized using cyproflanilide as the lead compound. The core bioactive scaffold was retained while integrating active substructure combination and pharmacophore fusion strategies. All compounds were characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. Preliminary bioassay data showed that some target compounds exhibited good insecticidal activity against <i>Plutella xylostella</i>, <i>Mythimna separata</i>, and <i>Tetranychus cinnabarinus</i>. Particularly, compound 7 g exhibited 100% lethality at a concentration of 1 mg/L against both <i>Plutella xylostella</i> and <i>Mythimna separata</i>; meanwhile, compound 7q achieved complete lethality against <i>Tetranychus cinnabarinus</i> at a concentration of 100 mg/L. Further structure–activity relationship (SAR) analysis based on in vitro efficacy data provided a theoretical foundation for developing next-generation acaricides/insecticides. These findings offer valuable insights for designing novel meta-diamide agrochemicals with enhanced efficacy.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 3","pages":"625 - 633"},"PeriodicalIF":3.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429356","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}