{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:01:33Z","timestamp":1785142893291,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    K\n                    <jats:sub>V<\/jats:sub>\n                    7.1 agonists are promising therapeutic agents for the treatment of hypertension, arrhythmia and preterm labor. The 3\u2010(indol\u20103\u2010ylmethyl) substituted 1,4\u2010benzodiazepine (R)\u2010L3 has been reported as a potent K\n                    <jats:sub>V<\/jats:sub>\n                    7.1 activator. In this study, (R)\u2010L3 was systematically modified at eight positions including the configuration at 3\u2010position. For the synthesis of the designed 1,4\u2010benzodiazepines\n                    <jats:bold>8<\/jats:bold>\n                    and\n                    <jats:bold>12<\/jats:bold>\n                    , 2\u2010aminobenzophenones\n                    <jats:bold>4<\/jats:bold>\n                    were reacted with amino acid derived 1,3\u2010oxazolidinediones\n                    <jats:bold>7<\/jats:bold>\n                    or\n                    <jats:bold>11<\/jats:bold>\n                    . The required 2\u2010aminobenzophenones\n                    <jats:bold>4<\/jats:bold>\n                    were obtained regioselectively by Sugasawa reaction of anilines\n                    <jats:bold>2<\/jats:bold>\n                    and\n                    <jats:bold>3<\/jats:bold>\n                    with various substituted benzonitriles, using BCl\n                    <jats:sub>3<\/jats:sub>\n                    and AlCl\n                    <jats:sub>3<\/jats:sub>\n                    . Racemization during deprotonation and alkylation of secondary lactams\n                    <jats:bold>8<\/jats:bold>\n                    and\n                    <jats:bold>12<\/jats:bold>\n                    was not observed. However, racemization occurred during conversion of lactam\n                    <jats:bold>8b<\/jats:bold>\n                    into thiolactam\n                    <jats:bold>17<\/jats:bold>\n                    . The enantiomers of thiolactam\n                    <jats:italic>rac<\/jats:italic>\n                    \u2010\n                    <jats:bold>17<\/jats:bold>\n                    and triazole\n                    <jats:italic>rac<\/jats:italic>\n                    \u2010\n                    <jats:bold>18<\/jats:bold>\n                    were separated by chiral HPLC. The ion channel modulatory activity of the resulting 1,4\u2010benzodiazepines was evaluated by two\u2010electrode voltage\u2010clamp (TEVC) experiments. These TEVC experiments showed that (3\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010configuration and the indolylmethyl moiety at 3\u2010position are essential for K\n                    <jats:sub>V<\/jats:sub>\n                    7.1 activation. High activity was observed for secondary lactam\n                    <jats:bold>8b<\/jats:bold>\n                    and methylated lactam\n                    <jats:bold>9b<\/jats:bold>\n                    , but larger N\u2010substituents reduced the channel activation. The thioamide (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010\n                    <jats:bold>17<\/jats:bold>\n                    and the triazole (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010\n                    <jats:bold>18<\/jats:bold>\n                    did not significantly activate the K\n                    <jats:sub>V<\/jats:sub>\n                    7.1 channel. Replacement of the F\u2010atom in 2\u2010position of the 5\u2010phenyl moiety by a proton or other halogen atoms reduced the K\n                    <jats:sub>V<\/jats:sub>\n                    7.1 activity. However, the 9\u2010hydroxy derivative\n                    <jats:bold>9i<\/jats:bold>\n                    appeared to exhibit higher agonistic activity (+68% activity increase at 1\u2009\u00b5M) than (R)\u2010L3 (\n                    <jats:bold>9b<\/jats:bold>\n                    , +45% at 1\u2009\u00b5M). Moreover, higher phase I metabolic stability was observed for phenol\n                    <jats:bold>9i<\/jats:bold>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/ardp.70268","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:59:34Z","timestamp":1780664374000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2013Activity Relationship Study on Ligands Activating the Voltage\u2010Gated Potassium Channel K\n                    <sub>V<\/sub>\n                    7.1"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9117-4314","authenticated-orcid":false,"given":"Florian","family":"Ro\u00dfner","sequence":"first","affiliation":[{"name":"GRK 2515, Chemical Biology of Ion Channels (Chembion) Universit\u00e4t M\u00fcnster  M\u00fcnster Germany"},{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-5373","authenticated-orcid":false,"given":"Guiscard","family":"Seebohm","sequence":"additional","affiliation":[{"name":"GRK 2515, Chemical Biology of Ion Channels (Chembion) Universit\u00e4t M\u00fcnster  M\u00fcnster Germany"},{"name":"Department of Cardiovascular Medicine, Institute for Genetics of Heart Diseases (IfGH) University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-8417","authenticated-orcid":false,"given":"Bernhard","family":"W\u00fcnsch","sequence":"additional","affiliation":[{"name":"GRK 2515, Chemical Biology of Ion Channels (Chembion) Universit\u00e4t M\u00fcnster  M\u00fcnster Germany"},{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.019"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00031.2005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00142"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/384080a0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/384078a0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01863.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.598779"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01021.x"},{"key":"e_1_2_10_10_1","unstructured":"J. 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