{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:23:48Z","timestamp":1760783028274,"version":"build-2065373602"},"reference-count":13,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2008,4,9]],"date-time":"2008-04-09T00:00:00Z","timestamp":1207699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2008,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The NK<jats:sub>2<\/jats:sub> receptor belongs to the family of tachykinin neurotransmitters. It has been reported to be involved in several pathological conditions, and selective antagonists are potentially useful drugs for the treatment of asthma, irritable bowel syndrome, cystitis, and depression. Starting from in\u2010house capped dipeptide libraries, we were able to identify a number of molecules with sub\u2010nanomolar binding affinity for the hNK<jats:sub>2<\/jats:sub> receptor. All were characterized by a rigid core structure with a strong constraint induced by an \u03b1,\u03b1\u2010cyclopentaneglycine fragment. Herein we report the further elaboration of three initial basic structures. The planar benzothiophene group was substituted with a series of biphenyl and heterobiphenyl moieties that are well tolerated in terms of receptor affinity. The new compounds also maintained good antagonist potency in an in\u2005vitro functional assay, and a number of them showed significant in\u2005vivo activity after intravenous administration in our guinea pig model.<\/jats:p>","DOI":"10.1002\/cmdc.200800018","type":"journal-article","created":{"date-parts":[[2008,4,9]],"date-time":"2008-04-09T15:18:19Z","timestamp":1207754299000},"page":"1048-1060","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["\u03b1,\u03b1\u2010Cyclopentaneglycine Dipeptides Capped with Biaryls as Tachykinin NK<sub>2<\/sub> Receptor Antagonists"],"prefix":"10.1002","volume":"3","author":[{"given":"Marina","family":"Porcelloni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"D'Andrea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Sisto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Ettorre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Madami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Altamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Meini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Fattori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,8]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1159\/000138512"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.7.3.343"},{"key":"e_1_2_6_3_2","unstructured":"Sanofi\u2013Aventis Information Meeting for 2007 Paris February 12 2008:http:\/\/en.sanofi\u2010aventis.com\/Images\/20080212_Results_2007_en."},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.06.053"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.02.016"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm070289w"},{"key":"e_1_2_6_7_2","unstructured":"Compound27and its biological activity have already been published (ref.\u2005[5]) and are reported herein for a better understanding of the SARs obtained."},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm040832y"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0108768106018167"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00108a019"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360330708"},{"key":"e_1_2_6_12_2","first-page":"10","volume":"11","author":"Toniolo C.","year":"1993","journal-title":"Janssen Chim. 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