{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T14:56:33Z","timestamp":1771167393547,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,9,23]],"date-time":"2006-09-23T00:00:00Z","timestamp":1158969600000},"content-version":"vor","delay-in-days":3918,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[1996,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The classical histamine H<jats:sub>1<\/jats:sub>\u2010receptor antagonists diphenhydramine (<jats:bold>3a<\/jats:bold>) and cyproheptadine (<jats:bold>9<\/jats:bold>) and their derivatives (<jats:bold>3b\u2014d, 10<\/jats:bold>) were connected with a 2\u2010guanidinothiazole containing structure (<jats:bold>28<\/jats:bold>) derived from the H<jats:sub>2<\/jats:sub>\u2010receptor antagonist tiotidine in order to obtain combined H<jats:sub>1<\/jats:sub>\u2010\/H<jats:sub>2<\/jats:sub>\u2010receptor antagonists. The two moieties were not directly linked together, but were separated by a polymethylene spacer and a polar group (nitroethenediamine or urea). Thus 12 compounds were obtained that proved <jats:italic>in vitro<\/jats:italic> to possess high H<jats:sub>1<\/jats:sub>\u2010 and H<jats:sub>2<\/jats:sub>\u2010receptor antagonist activity at the isolated guinea\u2010pig ileum (H<jats:sub>1<\/jats:sub>) and the isolated guinea\u2010pig right atrium (H<jats:sub>2<\/jats:sub>), respectively. The incorporation of the diphenhydramine as well as the cyproheptadine component provides high affinity to H<jats:sub>1<\/jats:sub>\u2010receptors. The tricyclic cyproheptadine and its 10,11\u2010dihydro derivative (<jats:bold>30\u201332, 34<\/jats:bold>), however, cause a decrease of H<jats:sub>2<\/jats:sub>\u2010receptor antagonist potency compared to the diphenhydramines (<jats:bold>29a\u2014d, 33a\u2014d<\/jats:bold>). Using nitroethenediamine as the polar group is apparently more favourable to H<jats:sub>1<\/jats:sub>\u2010 and H<jats:sub>2<\/jats:sub>\u2010receptor affinity as the urea function. All compounds elicit a dual mode of competitive and noncompetitive antagonism. Among the novel compounds the nitroethenediamines with 4\u2010fluoro\u2010 or 4\u2010methyl\u2010substituted diphenhydramine as H<jats:sub>1<\/jats:sub>\u2010receptor antagonist moiety (<jats:bold>29c, d<\/jats:bold>) display the most potent H<jats:sub>1<\/jats:sub>\u2010 and H<jats:sub>2<\/jats:sub>\u2010receptor antagonist effects. The presented concept is a very promising way to combine H<jats:sub>1<\/jats:sub>\u2010 and H<jats:sub>2<\/jats:sub>\u2010receptor antagonist properties in one molecule.<\/jats:p>","DOI":"10.1002\/ardp.19963290206","type":"journal-article","created":{"date-parts":[[2006,10,17]],"date-time":"2006-10-17T02:49:33Z","timestamp":1161053373000},"page":"87-94","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis and Pharmacology of Combined Histamine H<sub>1<\/sub>\u2010\/H<sub>2<\/sub>\u2010Receptor Antagonists Containing Diphenhydramine and Cyproheptadine Derivatives"],"prefix":"10.1002","volume":"329","author":[{"given":"Cornelia","family":"Wolf","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Schunack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,9,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1978.tb01714.x"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00981123"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1987.tb04095.x"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(05)80245-3"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.4700170143"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90063-9"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.2500\/108854186779047762"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00128a045"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00151a007"},{"key":"e_1_2_1_11_2","unstructured":"D. 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