{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T22:06:42Z","timestamp":1747174002229,"version":"3.40.5"},"reference-count":54,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Chem. Inf. Model."],"published-print":{"date-parts":[[2021,12,27]]},"DOI":"10.1021\/acs.jcim.1c01055","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T15:17:15Z","timestamp":1637767035000},"page":"5893-5905","source":"Crossref","is-referenced-by-count":3,"title":["Identification of Highly Selective Orexin 1 Receptor Antagonists Driven by Structure-Based Design"],"prefix":"10.1021","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1698-6017","authenticated-orcid":true,"given":"Uta","family":"Lessel","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany"}]},{"given":"Marco","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Research Italia S.a.s. di BI IT S.r.l., Via Giovanni Lorenzini 8, 20139 Milano, MI, Italy"}]},{"given":"Niklas","family":"Heine","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany"}]},{"given":"Chiara","family":"Marelli","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Research Italia S.a.s. di BI IT S.r.l., Via Giovanni Lorenzini 8, 20139 Milano, MI, Italy"}]},{"given":"Laura","family":"Carrettoni","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Research Italia S.a.s. di BI IT S.r.l., Via Giovanni Lorenzini 8, 20139 Milano, MI, Italy"}]},{"given":"Roland","family":"Pfau","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany"}]},{"given":"Esther","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-2501","authenticated-orcid":true,"given":"Doris","family":"Riether","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany"}]}],"member":"316","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"ref1\/cit1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80949-6"},{"key":"ref2\/cit2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.322"},{"key":"ref3\/cit3","doi-asserted-by":"publisher","DOI":"10.1002\/cne.1190"},{"key":"ref4\/cit4a","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81965-0"},{"key":"ref4\/cit4b","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81973-X"},{"key":"ref5\/cit5","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3837"},{"key":"ref6\/cit6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315542111"},{"key":"ref7\/cit7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00357"},{"key":"ref8\/cit8a","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041745"},{"key":"ref8\/cit8b","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12481"},{"key":"ref9\/cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.05.130"},{"key":"ref10\/cit10","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2016_49"},{"key":"ref11\/cit11","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.19"},{"key":"ref12\/cit12","doi-asserted-by":"publisher","DOI":"10.1021\/jm100541c"},{"key":"ref13\/cit13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136910"},{"key":"ref14\/cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.03.007"},{"key":"ref15\/cit15","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00008"},{"key":"ref16\/cit16","doi-asserted-by":"publisher","DOI":"10.1038\/nature04071"},{"key":"ref17\/cit17","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(00)00199-3"},{"key":"ref18\/cit18","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.09.106"},{"key":"ref19\/cit19","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.220392"},{"key":"ref20\/cit20","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14251"},{"key":"ref21\/cit21","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-00937-9"},{"key":"ref22\/cit22a","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(01)00343-2"},{"key":"ref22\/cit22b","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703953"},{"key":"ref23\/cit23","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201300003"},{"key":"ref24\/cit24","unstructured":"Janssen Pharmaceutica NV. Substituted 7-Azabicycles and Their Use as Orexin Receptor Modulators. WIPO Patent WO20141595912014."},{"key":"ref25\/cit25","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.0c00085"},{"key":"ref26\/cit26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.10.019"},{"key":"ref27\/cit27","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319120009"},{"key":"ref28\/cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2016.06.004"},{"key":"ref29\/cit29","doi-asserted-by":"publisher","DOI":"10.2174\/1381612823666170710151255"},{"key":"ref30\/cit30","doi-asserted-by":"publisher","DOI":"10.1021\/bi300136h"},{"key":"ref31\/cit31","doi-asserted-by":"publisher","DOI":"10.1038\/nature14035"},{"key":"ref32\/cit32","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3183"},{"key":"ref33\/cit33","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2017.11.005"},{"key":"ref34\/cit34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00127.x"},{"key":"ref35\/cit35","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01787"},{"key":"ref36\/cit36","unstructured":"Molecular Operating Environment (MOE), 2016.08; Chemical Computing Group Inc.: Montreal,\nQC, Canada, 2016."},{"key":"ref37\/cit37","unstructured":"Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision D.01; Gaussian, Inc.: Wallingford, CT, 2013."},{"key":"ref38\/cit38a","unstructured":"aSanta Fe, N. M. ROCS 3.2.2.2: OpenEye Scientific Software. http:\/\/www.eyesopen.com, 2017."},{"key":"ref38\/cit38b","doi-asserted-by":"publisher","DOI":"10.1021\/jm0603365"},{"key":"ref39\/cit39","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.09.062"},{"key":"ref40\/cit40","doi-asserted-by":"publisher","DOI":"10.1021\/jo9026269"},{"key":"ref41\/cit41","unstructured":"Distomer was\ndefined as inactive\nat OX1 based on the fact that the residual activity of 215 nM measured\nfor the distomer sample obtained from chiral separation as later eluting\nenantiomer can be attributed to 2.9% eutomer contained in this sample\n(measured enantiomeric excess = 94.2%)."},{"key":"ref43\/cit43a","unstructured":"aBoehringer Ingelheim International GmbH.  Novel N-[(pyrimidinyloxy)propanyl]benzamides. WO2017178338, 2017."},{"key":"ref43\/cit43b","unstructured":"bBoehringer Ingelheim International\nGmbH.  Novel N-[(pyrazinyloxy)propanyl]benzamides. WO2017178339, 2017."},{"key":"ref43\/cit43c","unstructured":"cBoehringer Ingelheim International\nGmbH.  Novel N-[(pyridyloxy)propanyl]benzamides. WO2017178340, 2017."},{"key":"ref43\/cit43d","unstructured":"dBoehringer Ingelheim International\nGmbH.  Novel N-[(pyrimidinylamino)propanyl]-\nand N-[(pyrazinylamino)propanyl]arylcarboxamides. WO2017178341, 2017."},{"key":"ref43\/cit43e","unstructured":"eBoehringer Ingelheim International\nGmbH.  Novel N-[(pyrimidinylamino)propanyl]-\nand N-[(pyridinylamino)propanyl]arylcarboxamides. WO2017178343, 2017."},{"key":"ref43\/cit43f","unstructured":"fBoehringer Ingelheim International\nGmbH.  Novel N-[(heteroaryloxy)propanyl]heteroaryl\ncarboxamides. WO2017178344, 2017."},{"key":"ref43\/cit43g","unstructured":"gBoehringer\nIngelheim International GmbH.  Novel N-(2,2-difluoroethyl)-N-[(pyrimidinylamino)propanyl]arylcarboxamides. WO2019063605, 2019."},{"key":"ref43\/cit43h","unstructured":"hBoehringer Ingelheim International\nGmbH.  Novel N-[(pyrimidinylamino)propanyl]- N-[(pyridylamino)propanyl]-\nand N-[(pyrazinylamino)propanyl]arylcarboxamides. WO2019025275, 2019."},{"key":"ref42\/cit42","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(93)90080-4"}],"container-title":["Journal of Chemical Information and Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.1c01055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T05:08:03Z","timestamp":1682658483000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jcim.1c01055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":54,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12,27]]}},"alternative-id":["10.1021\/acs.jcim.1c01055"],"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.1c01055","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"type":"print","value":"1549-9596"},{"type":"electronic","value":"1549-960X"}],"subject":[],"published":{"date-parts":[[2021,11,24]]}}}