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Insulin, a hormone secreted from pancreatic \u03b2\u2010cells, decreases blood glucose levels, and glucagon, a hormone secreted from pancreatic \u03b1\u2010cells, increases blood glucose levels by counterregulation of insulin through stimulation of hepatic glucose production. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, inhibition of the glucagon receptor is one strategy for the treatment of hyperglycemia in type 2 diabetes. In this paper, we report a series of biphenylsulfonamide derivatives that were designed, synthesized, and then evaluated by cAMP and hepatic glucose production assays as glucagon receptor antagonists. Of these, compound <jats:bold>7aB\u20103<\/jats:bold> decreased glucagon\u2010induced cAMP production and glucagon\u2010induced glucose production in the in vitro assays. Glucagon challenge tests and glucose tolerance tests showed that compound <jats:bold>7aB\u20103<\/jats:bold> significantly inhibited glucagon\u2010induced glucose increases and improved glucose tolerance. These results suggest that compound <jats:bold>7aB\u20103<\/jats:bold> has therapeutic potential for the treatment of type 2 diabetes.<\/jats:p>","DOI":"10.1111\/cbdd.13928","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T13:46:58Z","timestamp":1627307218000},"page":"733-750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis and anti\u2010diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists"],"prefix":"10.1111","volume":"98","author":[{"given":"Chang\u2010Yong","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy Gachon Institute of Pharmaceutical Science Gachon University Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hojung","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon Institute of Pharmaceutical Science Gachon University Incheon Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Young","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy Mokpo National University Muan\u2010gun Jeollanam\u2010do Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thi\u2010Thao\u2010Linh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon Institute of Pharmaceutical Science Gachon University Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han\u2010Joo","family":"Maeng","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon Institute of Pharmaceutical Science Gachon University Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoung","family":"Mee Lee","sequence":"additional","affiliation":[{"name":"Kwangdong Pharmaceutical Co., Ltd Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee\u2010Sook","family":"Jun","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon Institute of Pharmaceutical Science Gachon University Incheon Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute Gachon University Incheon Korea"},{"name":"Gachon Medical Research Institute Gil Hospital Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyun","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon Institute of Pharmaceutical Science Gachon University Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010008\u20107479\u20106"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463\u20101326.2011.01427.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2017.01.019"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/10606820213687"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2018.10.013"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2011.8.369"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09\u20109028"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/diaspect.27.2.100"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12958"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13020175"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129226"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/op9000862"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17414"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11030108"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00492.2002"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.131200398"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12446"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v6.i6.850"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)85474\u20106"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm7015599"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm058026u"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.12.090"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000197946.81754.0a"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906\u201011013\u201010383\u2010y"},{"key":"e_1_2_10_26_1","unstructured":"Ling A. 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