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However, intrinsic drawbacks are associated with this compound class and were systematically addressed in the presented study. It was possible to install polar functionalities and bioisosteric moieties at distinct sites of the molecules while maintaining TGF\u03b2\u2010inhibitory activities. The introduction of a 2\u2010amino group or 7\u2010<jats:italic>N<\/jats:italic>\u2010alkyl modification proved to be successful strategies. Aqueous solubility was improved by up to seven\u2010fold at pH\u20057.4 and 200\u2010fold at pH\u20053 relative to the parent ethyl 4\u2010(biphenyl\u20104\u2010yl)\u20102,7,7\u2010trimethyl\u20105\u2010oxo\u20101,4,5,6,7,8\u2010hexahydroquinoline\u20103\u2010carboxylate. The therapeutic potential of the presented DHPs was further underscored in view of a potential dual mode of action: The differentiation of committed human iPSC\u2010derived cardiac progenitor cells (CPCs) was potently stimulated, and the rescue of cardiac fibrosis phenotypes was observed in engineered heart tissue (EHT) constructs.<\/jats:p>","DOI":"10.1002\/cmdc.201900036","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T10:34:08Z","timestamp":1550226848000},"page":"810-822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Toward Second\u2010Generation Cardiomyogenic and Anti\u2010cardiofibrotic 1,4\u2010Dihydropyridine\u2010Class TGF\u03b2 Inhibitors"],"prefix":"10.1002","volume":"14","author":[{"given":"Daniel","family":"L\u00e4ngle","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology Technische Universit\u00e4t Dortmund  Otto-Hahn-Str. 4 44227 Dortmund Germany"},{"name":"Department of Pharmaceutical and Medicinal Chemistry Christian-Albrechts-Universit\u00e4t Kiel  Gutenbergstr. 76 24118 Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tessa R.","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Toxicology University Medical Center Hamburg-Eppendorf  Martinistr. 52 20246 Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Wesseler","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Technische Universit\u00e4t Dortmund  Otto-Hahn-Str. 4 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Reckzeh","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Technische Universit\u00e4t Dortmund  Otto-Hahn-Str. 4 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niklas","family":"Schaumann","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Technische Universit\u00e4t Dortmund  Otto-Hahn-Str. 4 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Drowley","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolic Diseases IMED Biotech Unit AstraZeneca Gothenburg  Pepparsleden 1 43\u2005183 M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Polla","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolic Diseases IMED Biotech Unit AstraZeneca Gothenburg  Pepparsleden 1 43\u2005183 M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alleyn T.","family":"Plowright","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolic Diseases IMED Biotech Unit AstraZeneca Gothenburg  Pepparsleden 1 43\u2005183 M\u00f6lndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc N.","family":"Hirt","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Toxicology University Medical Center Hamburg-Eppendorf  Martinistr. 52 20246 Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Eschenhagen","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Toxicology University Medical Center Hamburg-Eppendorf  Martinistr. 52 20246 Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5515-1821","authenticated-orcid":false,"given":"Dennis","family":"Schade","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology Technische Universit\u00e4t Dortmund  Otto-Hahn-Str. 4 44227 Dortmund Germany"},{"name":"Department of Pharmaceutical and Medicinal Chemistry Christian-Albrechts-Universit\u00e4t Kiel  Gutenbergstr. 76 24118 Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,28]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"\u00a0"},{"key":"e_1_2_7_2_2","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1242\/dev.040584","volume":"136","author":"Wharton K.","year":"2009","journal-title":"Development"},{"key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/nrd1580","volume":"3","author":"Yingling J. 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