{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:54:24Z","timestamp":1781758464088,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Photopharmacology offers a novel approach to eliminate side effects of chemotherapy treatment via site\u2010specific activation of light\u2010active anticancer agents, which are typically constructed by the installation of light\u2010cleavable or light\u2010switchable molecules onto known drugs or inhibitors. The light\u2010switchable drugs being able to reversibly control biological activities are more advantageous, but the design of such compounds is very challenging. We synthesized a small series of photoswitchable S\u2010arylsulfonylurea\u2010based EP4 antagonists by substituting a core structural unit of a potent EP4 antagonist, grapiprant. In vitro cell\u2010based EP4 activity studies revealed that all light\u2010induced\n                    <jats:italic>cis<\/jats:italic>\n                    isomers of these compounds are more potent than their\n                    <jats:italic>trans<\/jats:italic>\n                    isomers. Compound\n                    <jats:bold>3<\/jats:bold>\n                    , with an azopyrazole photoswitch and a\n                    <jats:italic>para<\/jats:italic>\n                    \u2010methyl substitution in the\n                    <jats:italic>S<\/jats:italic>\n                    \u2010phenyl ring, displayed the highest EP4 antagonism by its\n                    <jats:italic>cis<\/jats:italic>\n                    isomer and a considerably larger activity difference (ca. 1.8\u2010fold) between\n                    <jats:italic>trans<\/jats:italic>\n                    and\n                    <jats:italic>cis<\/jats:italic>\n                    photoisomers. It showed (near) complete photoisomerization (\u223c95%\u201398%) upon 365\u00a0nm (forward) and 520\u00a0nm (reverse) light irradiations. The metastable\n                    <jats:italic>cis<\/jats:italic>\n                    isomers demonstrated high thermal stability (t\n                    <jats:sub>1\/2<\/jats:sub>\n                    = 1\u20133 days). All compounds were resistant to photobleaching and showed impressive stability for reduction with glutathione (10\u00a0mM). This study constitutes a proof\u2010of\u2010concept to design photoswitchable EP4 antagonists, and the structure\u2010activity relationship revealed herein may help design more potent grapiprant derivatives.\n                  <\/jats:p>","DOI":"10.1002\/chem.202503349","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T13:27:48Z","timestamp":1767101268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Azoheteroarene\u2010Modified Grapiprants Serving as Photoswitchable EP4 Antagonists"],"prefix":"10.1002","volume":"32","author":[{"given":"Md. Akram","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Chemistry TCG Lifesciences Pvt. Ltd.  Kolkata India"},{"name":"Department of Chemistry University of Calcutta  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyajit","family":"Bera","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Calcutta  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajib","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Biology TCG Lifesciences Pvt. Ltd. Bengal Intelligent Park Ltd.  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanta Kumar","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Biology TCG Lifesciences Pvt. Ltd. Bengal Intelligent Park Ltd.  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