{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T21:53:25Z","timestamp":1775771605940,"version":"3.50.1"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100012592","name":"FRST","doi-asserted-by":"crossref","award":["C08X0209"],"award-info":[{"award-number":["C08X0209"]}],"id":[{"id":"10.13039\/100012592","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Technology New Zealand"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1016\/j.ejmech.2016.06.047","type":"journal-article","created":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T18:28:08Z","timestamp":1467397688000},"page":"442-451","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Synthesis and biological activities of d - chiro -inositol analogues with insulin-like actions"],"prefix":"10.1016","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2825-8746","authenticated-orcid":false,"given":"P.M.","family":"Rendle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Kassibawi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.A.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.B.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.A.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Falshaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.F.","family":"Painter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.M.","family":"Loomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2016.06.047_bib1","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/anie.201502227","article-title":"The \u201cother\u201d inositols and their phosphates: synthesis, biology, and medicine (with recent advances in myo-inositol chemistry)","volume":"55","author":"Thomas","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2016.06.047_bib2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2119\/molmed.2010.00107","article-title":"d-chiro-inositol glycans in insulin signaling and insulin resistance","volume":"16","author":"Larner","year":"2010","journal-title":"Mol. Med."},{"key":"10.1016\/j.ejmech.2016.06.047_bib3","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1210\/endo.132.2.8425484","article-title":"Chiroinositol deficiency and insulin resistance. II. Acute effects of d-chiroinositol administration in streptozotocin-diabetic rats, normal rats given a glucose load, and spontaneously insulin-resistant rhesus monkeys","volume":"132","author":"Ortmeyer","year":"1993","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejmech.2016.06.047_bib4","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1056\/NEJM199904293401703","article-title":"Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome","volume":"340","author":"Nestler","year":"1999","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ejmech.2016.06.047_bib5","doi-asserted-by":"crossref","first-page":"417","DOI":"10.4158\/EP.8.6.417","article-title":"Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome","volume":"8","author":"Iuorno","year":"2002","journal-title":"Endocr. Pract."},{"key":"10.1016\/j.ejmech.2016.06.047_bib6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/dmrr.218","article-title":"Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of \u201cinsulin mediators\u201d","volume":"17","author":"Shashkin","year":"2001","journal-title":"Diabetes Metab. Res. Rev."},{"key":"10.1016\/j.ejmech.2016.06.047_bib7","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/BF00418546","article-title":"Infusion of pH 2.0 d-chiro-inositol glycan insulin putative mediator normalizes plasma glucose in streptozotocin diabetic rats at a dose equivalent to insulin without inducing hypoglycaemia","volume":"39","author":"Fonteles","year":"1996","journal-title":"Diabetologia"},{"key":"10.1016\/j.ejmech.2016.06.047_bib8","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1210\/endo.132.2.8425485","article-title":"Chiroinositol deficiency and insulin resistance. III. Acute glycogenic and hypoglycemic effects of two inositol phosphoglycan insulin mediators in normal and streptozotocin-diabetic rats in\u00a0vivo","volume":"132","author":"Huang","year":"1993","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejmech.2016.06.047_bib9","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1006\/bmme.1997.2607","article-title":"Isolation and partial characterisation of insulin-mimetic inositol phosphoglycans from human liver","volume":"61","author":"Caro","year":"1997","journal-title":"Biochem. Mol. Med."},{"key":"10.1016\/j.ejmech.2016.06.047_bib10","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/0006-291X(87)90519-5","article-title":"Inositol glycan mimics the action of insulin on glucose utilization in rat adipocytes","volume":"149","author":"Saltiel","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejmech.2016.06.047_bib11","doi-asserted-by":"crossref","first-page":"15285","DOI":"10.1016\/S0021-9258(18)48172-0","article-title":"A\u00a0phospho-oligosaccharide mimics the effect of insulin to inhibit isoproterenol-dependent phosphorylation of phospholipid methyltransferase in isolated adipocytes","volume":"262","author":"Kelly","year":"1987","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib12","doi-asserted-by":"crossref","first-page":"16266","DOI":"10.1016\/S0021-9258(18)41995-3","article-title":"An inositol phosphate glycan derived from a Trypanosoma brucei glycosyl-phosphatidylinositol mimics some of the metabolic actions of insulin","volume":"267","author":"Misek","year":"1992","journal-title":"J.\u00a0Biol. Chem."},{"issue":"5","key":"10.1016\/j.ejmech.2016.06.047_bib13","first-page":"394","article-title":"d-chiro-Inositol attenuates epinephrine-stimulated hepatic glucose output in the isolated perfused liver independently of insulin","volume":"45","author":"Whiting","year":"2013","journal-title":"Horm. Metab. Res."},{"key":"10.1016\/j.ejmech.2016.06.047_bib14","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1021\/jm030071j","article-title":"Isolation, structure, synthesis, and bioactivity of a novel putative insulin mediator. A galactosamine chiro-inositol pseudo-disaccharide Mn2+ chelate with insulin-like activity","volume":"46","author":"Larner","year":"2003","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib15","doi-asserted-by":"crossref","first-page":"11067","DOI":"10.1021\/bi0508845","article-title":"Allosteric activation of protein phosphatase 2C by d-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action","volume":"44","author":"Brautigan","year":"2005","journal-title":"Biochemistry"},{"key":"10.1016\/j.ejmech.2016.06.047_bib16","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.bmc.2009.12.056","article-title":"Synthesis of C-glycoside analogues of beta-galactosamine-(1-->4)-3-O-methyl-d-chiro-inositol and assay as activator of protein phosphatases PDHP and PP2Calpha","volume":"18","author":"Hans","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib17","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s000180050485","article-title":"Signalling via caveolin: involvement in the cross-talk between phosphoinositolglycans and insulin","volume":"56","author":"Muller","year":"1999","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.ejmech.2016.06.047_bib18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/BF03401738","article-title":"Convergence and divergence of the signaling pathways for insulin and phosphoinositolglycans","volume":"4","author":"Muller","year":"1998","journal-title":"Mol. Med."},{"issue":"Pt 1","key":"10.1016\/j.ejmech.2016.06.047_bib19","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1042\/bj3300277","article-title":"Signalling pathways of an insulin-mimetic phosphoinositolglycan-peptide in muscle and adipose tissue","volume":"330","author":"Kessler","year":"1998","journal-title":"Biochem. J."},{"issue":"1","key":"10.1016\/j.ejmech.2016.06.047_bib20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1177\/1535370214543064","article-title":"The diabetic rat kidney mediates inosituria and selective urinary partitioning of d-chiro-inositol","volume":"240","author":"Chang","year":"2015","journal-title":"Exp. Biol. Med."},{"key":"10.1016\/j.ejmech.2016.06.047_bib21","doi-asserted-by":"crossref","first-page":"9988","DOI":"10.1073\/pnas.90.21.9988","article-title":"d-chiro-inositol metabolism in diabetes mellitus","volume":"90","author":"Ostlund","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2016.06.047_bib22","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2337\/diacare.29.02.06.dc05-1070","article-title":"Altered d-chiro-inositol urinary clearance in women with polycystic ovary syndrome","volume":"29","author":"Baillargeon","year":"2006","journal-title":"Diabetes Care"},{"key":"10.1016\/j.ejmech.2016.06.047_bib23","doi-asserted-by":"crossref","first-page":"7287","DOI":"10.1021\/jf0302153","article-title":"Buckwheat concentrate reduces serum glucose in streptozotocin-diabetic rats","volume":"51","author":"Kawa","year":"2003","journal-title":"J.\u00a0Agric. Food Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib24","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1073\/pnas.0509779103","article-title":"Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide","volume":"103","author":"Nascimento","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2016.06.047_bib25","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1517\/17425247.2012.662953","article-title":"Myo-inositol in a new pharmaceutical form: a step forward to a broader clinical use","volume":"9","author":"Carlomagno","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"10.1016\/j.ejmech.2016.06.047_bib26","first-page":"575","article-title":"The combined therapy with myo-inositol and d-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone","volume":"16","author":"Nordio","year":"2012","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2016.06.047_bib27","doi-asserted-by":"crossref","first-page":"4528","DOI":"10.1021\/ja00167a061","article-title":"Efficient synthetic routes to fluorinated isosteres of inositol and their effects on cellular growth","volume":"112","author":"Kozikowski","year":"1990","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2016.06.047_bib28","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1039\/b316506j","article-title":"Conformation inversion of an inositol derivative by use of silyl ethers: a modified route to 3,6-di-O-substituted-l-ido-tetrahydroxyazepane derivatives","volume":"2","author":"Painter","year":"2004","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib29","doi-asserted-by":"crossref","first-page":"9435","DOI":"10.1016\/S0040-4039(98)02187-X","article-title":"A\u00a0practical modification of the Barton-McCombie reaction and radical O- to S- rearrangement of xanthates","volume":"39","author":"Quiclet-Sire","year":"1998","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2016.06.047_bib30","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0008-6215(00)00192-0","article-title":"New syntheses of 1d- and 1l-1,2-anhydro-myo-inositol and assessment of their glycosidase inhibitory activities","volume":"329","author":"Falshaw","year":"2000","journal-title":"Carbohydr. Res."},{"key":"10.1016\/j.ejmech.2016.06.047_bib31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.bmc.2003.10.003","article-title":"Syntheses of tetrahydroxyazepanes from chiro-inositols and their evaluation as glycosidase inhibitors","volume":"12","author":"Painter","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib32","doi-asserted-by":"crossref","DOI":"10.1021\/cr990302n","article-title":"Carbohydrate structural determination by NMR spectroscopy: modern methods and limitations","volume":"100","author":"Duus","year":"2000","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2016.06.047_bib33","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1021\/ja01111a020","article-title":"Derivatives of d-mannohexodialdose (6-Aldo-d-Mannose)","volume":"75","author":"Ballou","year":"1953","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2016.06.047_bib34","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1039\/a908986a","article-title":"Short practical synthesis of (3R,4R,5R,6R)-tetrahydroxyazepane and (3S,4S,5S,6S)-tetrahydroxyazepane from d- and l-chiro-inositol, respectively","author":"Painter","year":"2000","journal-title":"J.\u00a0Chem. Soc. Perk T 1"},{"key":"10.1016\/j.ejmech.2016.06.047_bib35","doi-asserted-by":"crossref","first-page":"19521","DOI":"10.1074\/jbc.M200601200","article-title":"Hydroxylation and glycosylation of the four conserved lysine residues in the collagenous domain of adiponectin. Potential role in the modulation of its insulin-sensitizing activity","volume":"277","author":"Wang","year":"2002","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib36","doi-asserted-by":"crossref","first-page":"7579","DOI":"10.1016\/S0021-9258(17)34542-8","article-title":"Development of hormone receptors and hormone responsiveness in\u00a0vitro. Effect of prolonged insulin treatment on hexose uptake in 3T3-L1 adipocytes","volume":"253","author":"Rosen","year":"1978","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib37","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.peptides.2014.05.011","article-title":"\u03b1-Calcitonin gene related peptide (\u03b1-CGRP) mediated lipid mobilization in 3T3-L1 adipocytes","volume":"58C","author":"Walker","year":"2014","journal-title":"Peptides"},{"key":"10.1016\/j.ejmech.2016.06.047_bib38","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ab.2012.03.005","article-title":"Protocol for effective differentiation of 3T3-L1 cells to adipocytes","volume":"425","author":"Zebisch","year":"2012","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib39","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1080\/15604280212528","article-title":"d-chiro-inositol\u2013its functional role in insulin action and its deficit in insulin resistance","volume":"3","author":"Larner","year":"2002","journal-title":"Int. J. Exp. Diabetes Res."},{"key":"10.1016\/j.ejmech.2016.06.047_bib40","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1002\/hlca.19500330627","article-title":"Recherches Dans La Serie Des Cyclitols .13. Preparation Et Oxydation Biochimique Du D-Viburnitol","volume":"33","author":"Posternak","year":"1950","journal-title":"Helv. Chim. Acta"},{"key":"10.1016\/j.ejmech.2016.06.047_bib41","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0008-6215(00)81001-0","article-title":"Cyclitols.38. The preparation of cyclohexanepentols from inositols by deoxygenation","volume":"101","author":"Angyal","year":"1982","journal-title":"Carbohyd Res."},{"key":"10.1016\/j.ejmech.2016.06.047_bib42","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1016\/j.tet.2004.11.084","article-title":"Highly stereoselective and stereospecific syntheses of a variety of quercitols from d-(-)-quinic acid","volume":"61","author":"Shih","year":"2005","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2016.06.047_bib43","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1016\/S0021-9258(19)85559-X","article-title":"Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes","volume":"255","author":"Student","year":"1980","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2016.06.047_bib44","series-title":"CrysAlis Pro User Manual ENG","author":"Agilent","year":"2014"},{"key":"10.1016\/j.ejmech.2016.06.047_bib45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. C Struct. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523416305372?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523416305372?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T15:00:31Z","timestamp":1656774031000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523416305372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":45,"alternative-id":["S0223523416305372"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2016.06.047","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis and biological activities of d-chiro-inositol analogues with insulin-like actions","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2016.06.047","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}