{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:40:05Z","timestamp":1775198405153,"version":"3.50.1"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-10-2025-017"],"award-info":[{"award-number":["075-10-2025-017"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by intestinal endocrine L cells that activates the GLP-1 receptor (GLP-1R), leading to glucose-dependent insulin secretion and suppression of glucagon release. In recent years, GLP-1R agonists (GLP-1RAs) have become one of the leading therapeutic options for the treatment of type 2 diabetes mellitus; however, for a long time clinically approved GLP-1RAs were limited to peptide drugs unsuitable for oral administration. The discovery of the \u201cfirst-in-class\u201d small molecule agonist danuglipron in 2018 demonstrated the feasibility of orally available GLP-1RAs and stimulated the development of numerous danuglipron-like compounds, some of which showed increased efficacy over the prototype. In this study, we report the design and synthesis of novel GLP-1RAs based on a regioisomeric danuglipron scaffold, 1H-benzo[d]imidazole-5-carboxylic acid. A series of 35 compounds was synthesized and evaluated in vitro for cytotoxicity and GLP-1R agonistic activity using a cAMP accumulation assay. A potent lead compound 12r (pEC50 = 7.72, pCC50 &lt; 3.60) was found which is a close structural analog of danuglipron with reduced cytotoxicity and excellent selectivity over two other class B GPCRs, including GCGR and GIPR. Despite decreased potency compared to danuglipron, the obtained results hold promise for further optimization and provide valuable structure\u2013activity relationship insights.<\/jats:p>","DOI":"10.3390\/molecules31071129","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:57:24Z","timestamp":1774864644000},"page":"1129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Small Molecule GLP-1R Agonists Based on 1H-Benzo[d]imidazole-5-Carboxylic Acid Scaffold"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1039-5093","authenticated-orcid":false,"given":"Elena V.","family":"Tolkacheva","sequence":"first","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, Sirius 354340, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tagir L.","family":"Salakhov","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, Sirius 354340, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6724-135X","authenticated-orcid":false,"given":"Alexandr Yu.","family":"Saliev","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, Sirius 354340, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia D.","family":"Lebedeva","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, Sirius 354340, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa M.","family":"Krasnodubets","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, Sirius 354340, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-5652","authenticated-orcid":false,"given":"Eugene Y.","family":"Smirnov","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-6659","authenticated-orcid":false,"given":"Sergey A.","family":"Silonov","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-0802","authenticated-orcid":false,"given":"Konstantin V.","family":"Balakin","sequence":"additional","affiliation":[{"name":"Institute of Future Biophysics, Institutsky Lane, 9, Dolgoprudny 141700, Moscow Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-4398","authenticated-orcid":false,"given":"Vladimir V.","family":"Chernyshov","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, Sirius 354340, Krasnodar Region, Russia"},{"name":"Institute of Future Biophysics, Institutsky Lane, 9, Dolgoprudny 141700, Moscow Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9573-4183","authenticated-orcid":false,"given":"Roman A.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Medicinal Biotechnology Department, Sirius University of Science and Technology, Olimpiyskiy Ave. 1, Sirius 354340, Krasnodar Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","first-page":"44","article-title":"Positioning Glucagon-like-Peptide-1\u2014Based Treatments within an Optimal Management Regimen for Type 2 Diabetes","volume":"4","year":"2008","journal-title":"Eur. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1021\/acs.molpharmaceut.9b00308","article-title":"Glucagon-Like Peptide-1 Receptor Agonists and Strategies To Improve Their Efficiency","volume":"16","author":"Alavi","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"170749","DOI":"10.1016\/j.peptides.2022.170749","article-title":"GLP-1 and GIP Receptor Signaling in Beta Cells\u2014A Review of Receptor Interactions and Co-Stimulation","volume":"151","author":"Mayendraraj","year":"2022","journal-title":"Peptides"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3803\/EnM.2021.102","article-title":"Peptidyl and Non-Peptidyl Oral Glucagon-like Peptide-1 Receptor Agonists","volume":"36","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"116632","DOI":"10.1016\/j.ejmech.2024.116632","article-title":"Binding Sites and Design Strategies for Small Molecule GLP-1R Agonists","volume":"275","author":"Zhang","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sztanek, F., T\u00f3th, L.I., Pet\u0151, A., Herny\u00e1k, M., Di\u00f3szegi, \u00c1., and Harangi, M. (2024). New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes\u2014Beyond and within GLP-1 Receptor Agonists. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061320"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.7150\/ijbs.59965","article-title":"GLP-1 Receptor Agonists (GLP-1RAs): Cardiovascular Actions and Therapeutic Potential","volume":"17","author":"Ma","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Volke, V., Katus, U., Johannson, A., Toompere, K., Heinla, K., R\u00fcnkorg, K., and Uusk\u00fcla, A. (2022). Systematic Review and Meta-Analysis of Head-to-Head Trials Comparing Sulfonylureas and Low Hypoglycaemic Risk Antidiabetic Drugs. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-01158-5"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sharma, V., and Patial, V. (2022). Peroxisome Proliferator-Activated Receptor Gamma and Its Natural Agonists in the Treatment of Kidney Diseases. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.991059"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8809","DOI":"10.1038\/s41598-024-59390-z","article-title":"PPAR Agonists as Add-on Treatment with Metformin in Management of Type 2 Diabetes: A Systematic Review and Meta-Analysis","volume":"14","author":"Alnuaimi","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"135115","DOI":"10.1016\/j.molstruc.2023.135115","article-title":"Recent Developments in Synthetic \u03b1-Glucosidase Inhibitors: A Comprehensive Review with Structural and Molecular Insight","volume":"1281","author":"Singh","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110708","DOI":"10.1016\/j.biopha.2020.110708","article-title":"Type II Diabetes Mellitus: A Review on Recent Drug Based Therapeutics","volume":"131","author":"Padhi","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Artasensi, A., Pedretti, A., Vistoli, G., and Fumagalli, L. (2020). Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs. Molecules, 25.","DOI":"10.3390\/molecules25081987"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Salmen, T., Bobirca, F.-T., Bica, I.-C., Mihai, D.-A., Pop, C., and Stoian, A.P. (2023). The Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists in the Standard of Care Treatment of Type 2 Diabetes Mellitus. Life, 13.","DOI":"10.3390\/life13030839"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ma\u0142yszczak, A., Prze\u017adziecka-Do\u0142yk, J., Szyde\u0142ko-Pa\u015bko, U., and Misiuk-Hoj\u0142o, M. (2024). Novel Antidiabetic Drugs and the Risk of Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Clin. Med., 13.","DOI":"10.3390\/jcm13061797"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Salmen, T., Serbanoiu, L.I., Bica, I.C., Serafinceanu, C., Muzurovi\u0107, E., Janez, A., Busnatu, S., Banach, M., Rizvi, A.A., and Rizzo, M. (2023). A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy\u2014A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119760"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1136\/jnnp-2024-335593","article-title":"Glucagon-like Peptide-1 Receptor Agonists for Major Neurocognitive Disorders","volume":"96","author":"Ghenciulescu","year":"2025","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lv, D., Feng, P., Guan, X., Liu, Z., Li, D., Xue, C., Bai, B., and H\u00f6lscher, C. (2024). Neuroprotective Effects of GLP-1 Class Drugs in Parkinson\u2019s Disease. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1462240"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Iacobini, C., Vitale, M., Haxhi, J., Pesce, C., Pugliese, G., and Menini, S. (2022). Food-Related Carbonyl Stress in Cardiometabolic and Cancer Risk Linked to Unhealthy Modern Diet. Nutrients, 14.","DOI":"10.3390\/nu14051061"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113537","DOI":"10.1016\/j.intimp.2024.113537","article-title":"Neuroprotective Effects of GLP-1 Receptor Agonists in Neurodegenerative Disorders: A Large-Scale Propensity-Matched Cohort Study","volume":"143","author":"Siddeeque","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Greco, E.V., Russo, G., Giandalia, A., Viazzi, F., Pontremoli, R., and De Cosmo, S. (2019). GLP-1 Receptor Agonists and Kidney Protection. Medicina, 55.","DOI":"10.3390\/medicina55060233"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e462","DOI":"10.1002\/edm2.462","article-title":"Glucagon-like Peptide Agonists: A Prospective Review","volume":"7","author":"Mariam","year":"2024","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hu, E.-H., Tsai, M.-L., Lin, Y., Chou, T.-S., and Chen, T.-H. (2024). A Review and Meta-Analysis of the Safety and Efficacy of Using Glucagon-like Peptide-1 Receptor Agonists. Medicina, 60.","DOI":"10.3390\/medicina60030357"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s40262-021-01025-x","article-title":"Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials","volume":"60","author":"Overgaard","year":"2021","journal-title":"Clin. Pharmacokinet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.2174\/0929867330666230416153301","article-title":"The Discovery and Development of Glucagon-Like Peptide-1 Receptor Agonists","volume":"31","author":"Fang","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1021\/jm201150j","article-title":"Cyclobutane Derivatives as Novel Nonpeptidic Small Molecule Agonists of Glucagon-like Peptide-1 Receptor","volume":"55","author":"Liu","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1021\/acs.jmedchem.1c01842","article-title":"Discovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for \u201cDiabesity\u201d","volume":"65","author":"Decara","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/cbdd.14039","article-title":"2-Aminothiophene Derivatives as a New Class of Positive Allosteric Modulators of Glucagon-like Peptide 1 Receptor","volume":"99","author":"Redij","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1080\/13543776.2020.1811851","article-title":"GLP-1R Agonists for the Treatment of Obesity: A Patent Review (2015\u2013Present)","volume":"30","author":"Liu","year":"2020","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yang, X., Zhang, M., Lu, Z., Zhi, L., Xue, H., Liu, T., Liu, M., Cui, L., Liu, Z., and He, P. (2021). Novel Small Molecule Glucagon-Like Peptide-1 Receptor Agonist S6 Stimulates Insulin Secretion From Rat Islets. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.664802"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1021\/acsomega.8b03052","article-title":"Structural Modeling and in Silico Screening of Potential Small-Molecule Allosteric Agonists of a Glucagon-like Peptide 1 Receptor","volume":"4","author":"Redij","year":"2019","journal-title":"ACS Omega"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s12272-013-0253-9","article-title":"Synthesis and Biological Evaluation of Glucagon-like Peptide-1 Receptor Agonists","volume":"37","author":"Zhang","year":"2014","journal-title":"Arch. Pharm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.bbrc.2011.12.004","article-title":"Two Small Molecule Agonists of Glucagon-like Peptide-1 Receptor Modulate the Receptor Activation Response Differently","volume":"417","author":"Cheong","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.2147\/DDDT.S404055","article-title":"Cinchonine, a Potential Oral Small-Molecule Glucagon-Like Peptide-1 Receptor Agonist, Lowers Blood Glucose and Ameliorates Non-Alcoholic Steatohepatitis","volume":"17","author":"Xue","year":"2023","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8208","DOI":"10.1021\/acs.jmedchem.1c01856","article-title":"A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor","volume":"65","author":"Griffith","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_36","unstructured":"Aspnes, G.E., Bagley, S.W., Curto, J.M., Dowling, M.S., Edmonds, D.J., Flanagan, M.E., Futatsugi, K., Griffith, T.A., Huard, K., and Ingle, G. (2018). GLP-1 Receptor Agonists and Uses Thereof. (WO 2018\/109607)."},{"key":"ref_37","unstructured":"Aspnes, G.E., Bagley, S.W., Curto, J.M., Edmonds, D.J., Flanagan, M.E., Futatsugi, K., Griffith, T.A., Huard, K., Lian, Y., and Limberakis, C. (2019). GLP-1 Receptor Agonists and Uses Thereof. (WO 2019\/239319)."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29959","DOI":"10.1073\/pnas.2014879117","article-title":"Structural Basis for GLP-1 Receptor Activation by LY3502970, an Orally Active Nonpeptide Agonist","volume":"117","author":"Kawai","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","unstructured":"Yoshino, H., Tsuchiya, S., Matsuo, A., Sato, T., Nishimoto, M., Oguri, K., Ogawa, H., Nishimura, Y., Furuta, Y., and Kashiwagi, H. (2018). Pyrazolopyridine Derivative Having GLP-1 Receptor Agonist Effect. (WO 2018\/056453)."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/dom.16005","article-title":"Evaluation of an Oral Small-molecule Glucagon-like Peptide-1 Receptor Agonist, Lotiglipron, for Type 2 Diabetes and Obesity: A Dose-ranging, Phase 2, Randomized, Placebo-controlled Study","volume":"27","author":"Amin","year":"2025","journal-title":"Diabetes Obes. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1111\/dom.16534","article-title":"Efficacy and Safety of Danuglipron (PF-06882961) in Adults with Obesity: A Randomized, Placebo-Controlled, Dose-Ranging Phase 2b Study","volume":"27","author":"Buckeridge","year":"2025","journal-title":"Diabetes Obes. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1056\/NEJMoa2505669","article-title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes","volume":"393","author":"Rosenstock","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tolkacheva, E.V., Saliev, A.Y., Salakhov, T.L., Balakin, K.V., Ivanov, R.A., and Chernyshov, V.V. (2025). \u201cNext-in-Class\u201d GLP-1R Danuglipron- and Lotiglipron-like Agonists: A Patent Review (2020\u20132024). Curr. Med. Chem.","DOI":"10.2174\/0109298673366258250710101146"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7988","DOI":"10.1021\/acs.jmedchem.3c00320","article-title":"Discovery of Novel 5,6-Dihydro-1,2,4-Triazine Derivatives as Efficacious Glucagon-Like Peptide-1 Receptor Agonists","volume":"66","author":"Chen","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9555","DOI":"10.1021\/acs.jmedchem.5c00242","article-title":"Discovery and Evaluation of DA-302168S as an Efficacious Oral Small-Molecule Glucagon-Like Peptide-1 Receptor Agonist","volume":"68","author":"Dong","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7662","DOI":"10.1021\/acs.jmedchem.5c00231","article-title":"Discovery of New Difluorocyclobutyl Derivatives as Effective Glucagon-Like Peptide-1 Receptor Agonists with Reduced HERG Inhibitory Activities","volume":"68","author":"Miao","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s11030-025-11213-7","article-title":"Discovery and Optimization of Novel Indolecarboxylic Acid Derivative as Potent Glucagon-like Peptide-1 Receptor Agonists","volume":"30","author":"Zhao","year":"2025","journal-title":"Mol. Divers."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3386","DOI":"10.1021\/acs.jmedchem.4c02616","article-title":"Discovery of Selenium-Containing Derivatives as Potent and Orally Bioavailable GLP-1R Agonists","volume":"68","author":"Chen","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"14820","DOI":"10.1021\/acs.jmedchem.4c01177","article-title":"Design and Evaluation of 3-Phenyloxetane Derivative Agonists of the Glucagon-Like Peptide-1 Receptor","volume":"67","author":"Zhang","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"129454","DOI":"10.1016\/j.bmcl.2023.129454","article-title":"6-Azaspiro[2.5]Octanes as Small Molecule Agonists of the Human Glucagon-like Peptide-1 Receptor","volume":"94","author":"Aspnes","year":"2023","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"117761","DOI":"10.1016\/j.bmc.2024.117761","article-title":"A Novel Approach to Exploit Small-Molecule Glucagon-like Peptide-1 Receptor Agonists with High Potency","volume":"107","author":"Wang","year":"2024","journal-title":"Bioorganic Med. Chem."},{"key":"ref_52","unstructured":"Meng, Q., Xing, W., and Jennings, A. (2023). Heterocyclic GLP-1 Agonists. (WO 2023\/198140)."},{"key":"ref_53","unstructured":"Liang, B., Yang, Y., Wang, P., Yang, B., Lai, Y., and Wu, J.J. (2023). GLP-1 Receptor Modulating Compounds. (US 2023\/0271949)."},{"key":"ref_54","unstructured":"Xing, W., Lin, X., and Jennings, A. (2022). Heterocyclic GLP-1 Agonists. (WO 2022\/078407)."},{"key":"ref_55","unstructured":"Lin, X., Meng, Q., and Zhang, H. (2023). GLP-1 Receptor Agonists and Uses Thereof. (WO 2023\/179542)."},{"key":"ref_56","unstructured":"Lee, H.K., Hwang, J.-U., Lee, K.-H., Choi, H.-H., Jang, J.-I., Lee, H.-J., Kang, S.-T., Yoon, H.-H., Ha, N., and La, H.-H. (2020). GLP-1 Receptor Agonist. (WO 2021\/112538)."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"117935","DOI":"10.1016\/j.ejmech.2025.117935","article-title":"1,2,4-Oxadiazoles in Medicinal Chemistry: Trends of the Last Years","volume":"297","author":"Cherkasova","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Patel, M., Avashthi, G., Gacem, A., Alqahtani, M.S., Park, H.K., and Jeon, B.H. (2023). A Review of Approaches to the Metallic and Non-Metallic Synthesis of Benzimidazole (BnZ) and Their Derivatives for Biological Efficacy. Molecules, 28.","DOI":"10.3390\/molecules28145490"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/ejoc.202001397","article-title":"Unexpected Ring Opening During the Imination of Camphor-Type Bicyclic Ketones","volume":"2021","author":"Chernyshov","year":"2021","journal-title":"Eur. J. Org. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14151","DOI":"10.1039\/D2SC04341F","article-title":"Molecular Flavin Catalysts for C\u2013H Functionalisation and Derivatisation of Dehydroamino Acids","volume":"13","author":"Rehpenn","year":"2022","journal-title":"Chem. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11533","DOI":"10.1039\/c3cc46239k","article-title":"On the Antitumor Properties of Novel Cyclometalated Benzimidazole Ru(II), Ir(III) and Rh(III) Complexes","volume":"49","author":"Yellol","year":"2013","journal-title":"Chem. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.1016\/S0040-4039(02)01754-9","article-title":"Efficient Solution Phase Synthesis of 2-(N-Acyl)-Aminobenzimidazoles","volume":"43","author":"Seth","year":"2002","journal-title":"Tetrahedron Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1021\/acs.joc.2c02770","article-title":"Chemoselective Ru-Catalyzed Oxidative Lactamization vs Hydroamination of Alkynylamines: Insights from Experimental and Density Functional Theory Studies","volume":"88","author":"Varela","year":"2023","journal-title":"J. Org. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1016\/j.bmc.2015.04.013","article-title":"Novel Type of Plasmin Inhibitors: Providing Insight into P4 Moiety and Alternative Scaffold to Pyrrolopyrimidine","volume":"23","author":"Teno","year":"2015","journal-title":"Bioorganic Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1177\/1747519819899067","article-title":"Design, Synthesis, and Antitumor Activity of Novel Benzoheterocycle Derivatives as Inhibitors of Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase","volume":"44","author":"Ding","year":"2020","journal-title":"J. Chem. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1021\/acs.orglett.7b00615","article-title":"Diazaphenoxazines and Diazaphenothiazines: Synthesis of the \u201cCorrect\u201d Isomers Reveals They Are Highly Reactive Radical-Trapping Antioxidants","volume":"19","author":"Haidasz","year":"2017","journal-title":"Org. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"14563","DOI":"10.1002\/chem.201702877","article-title":"Cyclopalladation in the Periphery of a NHC Ligand as the Crucial Step in the Synthesis of Highly Active Suzuki\u2013Miyaura Cross-Coupling Catalysts","volume":"23","author":"Fizia","year":"2017","journal-title":"Chem. A Eur. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1021\/jm401552y","article-title":"Heat Shock Protein 70 Inhibitors. 2. 2,5\u2032-Thiodipyrimidines, 5-(Phenylthio)Pyrimidines, 2-(Pyridin-3-Ylthio)Pyrimidines, and 3-(Phenylthio)Pyridines as Reversible Binders to an Allosteric Site on Heat Shock Protein 70","volume":"57","author":"Taldone","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1007\/s11172-025-4639-x","article-title":"Synthesis of New 4-(5-R-1-Phenyl-1H-1,2,4-Triazol-3-Yl)Benzamides","volume":"74","author":"Firsova","year":"2025","journal-title":"Russ. Chem. Bull."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/S0040-4039(00)02288-7","article-title":"Synthesis of 3,5-Disubstituted-1,2,4-Oxadiazoles Using Tetrabutylammonium Fluoride as a Mild and Efficient Catalyst","volume":"42","author":"Gangloff","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhukovets, A.A., Chernyshov, V.V., Al\u2019mukhametov, A.Z., Seregina, T.A., Revtovich, S.V., Kasatkina, M.A., Isakova, Y.E., Kulikova, V.V., Morozova, E.A., and Cherkasova, A.I. (2024). Novel Hydroxamic Acids Containing Aryl-Substituted 1,2,4- or 1,3,4-Oxadiazole Backbones and an Investigation of Their Antibiotic Potentiation Activity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010096"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"128465","DOI":"10.1016\/j.bmcl.2021.128465","article-title":"Novel O-Acylated Amidoximes and Substituted 1,2,4-Oxadiazoles Synthesised from (+)-Ketopinic Acid Possessing Potent Virus-Inhibiting Activity against Phylogenetically Distinct Influenza A Viruses","volume":"55","author":"Chernyshov","year":"2022","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Marzook, A., Tomas, A., and Jones, B. (2021). The Interplay of Glucagon-Like Peptide-1 Receptor Trafficking and Signalling in Pancreatic Beta Cells. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.678055"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2337\/diabetes.53.1.5","article-title":"A New CAMP-Binding Protein in Support of Glucagon-like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic Beta-Cell","volume":"53","author":"Holz","year":"2004","journal-title":"Diabetes"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8392","DOI":"10.1073\/pnas.90.18.8392","article-title":"Production of High-Titer Helper-Free Retroviruses by Transient Transfection","volume":"90","author":"Pear","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1129\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T04:30:17Z","timestamp":1775190617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":75,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["molecules31071129"],"URL":"https:\/\/doi.org\/10.3390\/molecules31071129","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]}}}