{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:06:13Z","timestamp":1760853973666,"version":"3.44.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81320108029","81773995"],"award-info":[{"award-number":["81320108029","81773995"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Starting Foundation for Ph.D."},{"DOI":"10.13039\/501100008366","name":"Guangdong Pharmaceutical University","doi-asserted-by":"publisher","award":["43540073"],"award-info":[{"award-number":["43540073"]}],"id":[{"id":"10.13039\/501100008366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.bioorg.2018.01.039","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T12:28:45Z","timestamp":1517488125000},"page":"429-435","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"special_numbering":"C","title":["Structure-based optimization of free fatty acid receptor 1 agonists bearing thiazole scaffold"],"prefix":"10.1016","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8067-9700","authenticated-orcid":false,"given":"Zheng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2018.01.039_b0005","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus","volume":"58","author":"DeFronzo","year":"2009","journal-title":"Diabetes"},{"key":"10.1016\/j.bioorg.2018.01.039_b0010","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(11)60679-X","article-title":"Burden Metab Risk Factors, National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants","volume":"378","author":"Danaei","year":"2011","journal-title":"Lancet"},{"key":"10.1016\/j.bioorg.2018.01.039_b0015","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1001\/jama.2010.405","article-title":"Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes","volume":"303","author":"Phung","year":"2010","journal-title":"JAMA"},{"key":"10.1016\/j.bioorg.2018.01.039_b0020","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2174\/092986708783330656","article-title":"Type 2 diabetes and oral antihyperglycemic drugs","volume":"15","author":"Avery","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0025","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nrendo.2011.10","article-title":"Type 2 diabetes mellitus\u2014current therapies and the emergence of surgical options","volume":"7","author":"Lebovitz","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.bioorg.2018.01.039_b0030","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1517\/14740338.2013.752813","article-title":"A review of the efficacy and safety of oral antidiabetic drugs","volume":"12","author":"Stein","year":"2013","journal-title":"Expert Opin. Drug Saf."},{"key":"10.1016\/j.bioorg.2018.01.039_b0035","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0140-6736(11)60207-9","article-title":"Management of type 2 diabetes: new and future developments in treatment","volume":"378","author":"Tahrani","year":"2011","journal-title":"Lancet"},{"key":"10.1016\/j.bioorg.2018.01.039_b0040","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1517\/17460441.2014.941352","article-title":"Novel approaches to drug discovery for the treatment of type 2 diabetes","volume":"9","author":"Xu","year":"2014","journal-title":"Expert Opin. Drug Dis."},{"key":"10.1016\/j.bioorg.2018.01.039_b0045","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1007\/s00125-015-3541-8","article-title":"Medications for type 2 diabetes: how will we be treating patients in 50 years?","volume":"58","author":"Kahn","year":"2015","journal-title":"Diabetologia"},{"key":"10.1016\/j.bioorg.2018.01.039_b0050","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature01478","article-title":"Free fatty acids regulate insulin secretion from pancreatic \u03b2 cells through GPR40","volume":"422","author":"Itoh","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.bioorg.2018.01.039_b0055","doi-asserted-by":"crossref","first-page":"11303","DOI":"10.1074\/jbc.M211495200","article-title":"The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids","volume":"278","author":"Briscoe","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0060","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/pr.108.00802","article-title":"International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and-3: pharmacology and pathophysiological functions","volume":"60","author":"Stoddart","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.bioorg.2018.01.039_b0065","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1124\/mol.109.055244","article-title":"Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients","volume":"76","author":"Wellendorph","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.bioorg.2018.01.039_b0070","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbrc.2005.07.042","article-title":"Role of GPR40 in fatty acid action on the \u03b2 cell line INS-1E","volume":"335","author":"Shapiro","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.bioorg.2018.01.039_b0075","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1152\/ajpendo.00035.2005","article-title":"Oleic acid interacts with GPR40 to induce Ca2+ signaling in rat islet \u03b2-cells: mediation by PLC and L-type Ca2+ channel and link to insulin release","volume":"289","author":"Fujiwara","year":"2005","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.bioorg.2018.01.039_b0080","doi-asserted-by":"crossref","first-page":"25912","DOI":"10.1038\/srep25912","article-title":"Potentiation of glucose-stimulated insulin secretion by the GPR40-PLC-TRPC pathway in pancreatic beta-cells","volume":"6","author":"Yamada","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2018.01.039_b0085","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1021\/ml1000855","article-title":"Discovery of TAK-875: a potent, selective, and orally bioavailable GPR40 agonist","volume":"1","author":"Negoro","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0090","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1021\/jm2016123","article-title":"Discovery of phenylpropanoic acid derivatives containing polar functionalities as potent and orally bioavailable G protein-coupled receptor 40 agonists for the treatment of type 2 diabetes","volume":"55","author":"Mikami","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0095","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1021\/jm2012968","article-title":"Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that act as G protein-coupled receptor 40\/free fatty acid receptor 1 agonists","volume":"55","author":"Negoro","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0100","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1021\/jm300170m","article-title":"Optimization of (2, 3-dihydro-1-benzofuran-3-yl) acetic acids: discovery of a non-free fatty acid-like, highly bioavailable G protein-coupled receptor 40\/free fatty acid receptor 1 agonist as a glucose-dependent insulinotropic agent","volume":"55","author":"Negoro","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0105","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1016\/j.bmcl.2006.12.084","article-title":"Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor","volume":"17","author":"McKeown","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0110","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.bmcl.2011.10.118","article-title":"AMG 837: a potent, orally bioavailable GPR40 agonist","volume":"22","author":"Houze","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0115","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1021\/ml300133f","article-title":"Discovery of AM-1638: a potent and orally bioavailable GPR40\/FFA1 full agonist","volume":"3","author":"Brown","year":"2012","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0120","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1021\/ml300427u","article-title":"Discovery and optimization of potent GPR40 full agonists containing tricyclic spirocycles","volume":"4","author":"Wang","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0125","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1016\/j.bmcl.2014.05.019","article-title":"Recent developments in the discovery of FFA1 receptor agonists as novel oral treatment for type 2 diabetes mellitus","volume":"24","author":"Defossa","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0130","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ejmech.2016.02.040","article-title":"Design, synthesis and Structure-activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes","volume":"113","author":"Li","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0135","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1080\/13543784.2016.1189530","article-title":"Free fatty acid receptor agonists for the treatment of type 2 diabetes: drugs in preclinical to phase II clinical development","volume":"25","author":"Li","year":"2016","journal-title":"Expert Opin. Invest. Drug"},{"key":"10.1016\/j.bioorg.2018.01.039_b0140","article-title":"Free Fatty Acid Receptor 1 (FFAR1) as an emerging therapeutic target for type 2 diabetes mellitus: recent progress and prevailing challenges","author":"Li","year":"2017","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.bioorg.2018.01.039_b0145","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.bmc.2016.03.014","article-title":"Discovery of novel pyrrole-based scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists for the treatment of type 2 diabetes","volume":"24","author":"Li","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0150","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1016\/j.bmc.2016.08.068","article-title":"Discovery of novel free fatty acid receptor 1 agonists bearing triazole core via click chemistry","volume":"24","author":"Li","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0155","doi-asserted-by":"crossref","first-page":"46356","DOI":"10.1039\/C6RA07356E","article-title":"Discovery of a novel oxime ether scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists","volume":"6","author":"Li","year":"2016","journal-title":"RSC Adv."},{"key":"10.1016\/j.bioorg.2018.01.039_b0160","doi-asserted-by":"crossref","first-page":"6666","DOI":"10.1016\/j.bmc.2015.09.010","article-title":"Design, synthesis and structure-activity relationship studies of novel phenoxyacetamide-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes","volume":"23","author":"Li","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0165","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1016\/j.bmc.2017.03.001","article-title":"Design, synthesis and structure-activity relationship studies of novel free fatty acid receptor 1 agonists bearing amide linker","volume":"25","author":"Yang","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0170","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ejmech.2017.07.001","article-title":"Discovery of phenylsulfonyl acetic acid derivatives with improved efficacy and safety as potent free fatty acid receptor 1 agonists for the treatment of type 2 diabetes","volume":"138","author":"Li","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0175","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.bioorg.2017.12.012","article-title":"Design, synthesis, and biological evaluation of deuterated phenylpropionic acid derivatives as potent and long-acting free fatty acid receptor 1 agonists","volume":"76","author":"Li","year":"2018","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0180","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S1359-6446(04)03069-7","article-title":"Ligand efficiency: a useful metric for lead selection","volume":"9","author":"Hopkins","year":"2004","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.bioorg.2018.01.039_b0185","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nrd2445","article-title":"The influence of drug-like concepts on decision-making in medicinal chemistry","volume":"6","author":"Leeson","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bioorg.2018.01.039_b0190","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2012.09.019","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"64","author":"Lipinski","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.bioorg.2018.01.039_b0195","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.1021\/jm2005699","article-title":"Identification of a potent and selective free fatty acid receptor 1 (FFA1\/GPR40) agonist with favorable physicochemical and in vitro ADME properties","volume":"54","author":"Christiansen","year":"2011","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2018.01.039_b0200","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1517\/17460441003605098","article-title":"Lipophilicity in drug discovery","volume":"5","author":"Waring","year":"2010","journal-title":"Expert Opin. Drug Dis."},{"key":"10.1016\/j.bioorg.2018.01.039_b0205","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd2796","article-title":"The influence of lead discovery strategies on the properties of drug candidates","volume":"8","author":"Keser\u00fc","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bioorg.2018.01.039_b0210","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1021\/acsmedchemlett.5b00157","article-title":"Molecular property design: does everyone get it?","volume":"6","author":"Leeson","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0215","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.1080\/00397910701574908","article-title":"Rapid and catalyst-free \u03b1-halogenation of ketones using N-halosuccinamides in DMSO","volume":"37","author":"Sreedhar","year":"2007","journal-title":"Synth. Commun."},{"key":"10.1016\/j.bioorg.2018.01.039_b0220","doi-asserted-by":"crossref","first-page":"11176","DOI":"10.1021\/ja052934z","article-title":"Total synthesis of thiostrepton. Assembly of key building blocks and completion of the synthesis","volume":"127","author":"Nicolaou","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bioorg.2018.01.039_b0225","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1016\/j.tetlet.2004.06.034","article-title":"A simple reduction of methyl aromatic esters to alcohols using sodium borohydride\u2013methanol system","volume":"45","author":"Boechat","year":"2004","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.bioorg.2018.01.039_b0230","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/nature13494","article-title":"High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875","volume":"513","author":"Srivastava","year":"2014","journal-title":"Nature"}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206817309604?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206817309604?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T07:49:12Z","timestamp":1758613752000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206817309604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":46,"alternative-id":["S0045206817309604"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2018.01.039","relation":{},"ISSN":["0045-2068"],"issn-type":[{"type":"print","value":"0045-2068"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure-based optimization of free fatty acid receptor 1 agonists bearing thiazole scaffold","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2018.01.039","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}