{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:25:32Z","timestamp":1784773532744,"version":"3.55.0"},"reference-count":20,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2022,6]]},"DOI":"10.1016\/j.bmcl.2022.128728","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T11:08:40Z","timestamp":1649502520000},"page":"128728","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Optimisation of momelotinib with improved potency and efficacy as pan-JAK inhibitor"],"prefix":"10.1016","volume":"66","author":[{"given":"Jigar","family":"Desai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaumin","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Gite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Panchal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Gite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Argade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeevan","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Sachchidanand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debdutta","family":"Bandyopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnarup","family":"Ghoshdastidar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoshang","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jogeshwar","family":"Mahapatra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoranjan","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Giri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukul","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.bmcl.2022.128728_b0005","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.immuni.2012.03.016","article-title":"Inborn errors of human JAKs and STATs","volume":"36","author":"Casanova","year":"2012","journal-title":"Immunity."},{"issue":"10","key":"10.1016\/j.bmcl.2022.128728_b0010","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1016\/j.molimm.2006.11.025","article-title":"Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease","volume":"44","author":"O'Sullivan","year":"2007","journal-title":"Mol Immunol."},{"key":"10.1016\/j.bmcl.2022.128728_b0015","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-065X.2008.00754.x","article-title":"Janus kinases in immune cell signaling","volume":"228","author":"Kamran","year":"2009","journal-title":"Immunol Rev."},{"issue":"5","key":"10.1016\/j.bmcl.2022.128728_b0020","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11926-009-0054-9","article-title":"Intracellular signal pathways: potential for therapies","volume":"11","author":"Mavers","year":"2009","journal-title":"Curr Rheumatol Rep."},{"issue":"12","key":"10.1016\/j.bmcl.2022.128728_b0025","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2004-5-12-253","article-title":"The Janus Kinases (JAKs)","volume":"5","author":"Yamaoka","year":"2004","journal-title":"Genome Biol."},{"issue":"20","key":"10.1016\/j.bmcl.2022.128728_b0030","doi-asserted-by":"crossref","first-page":"8973","DOI":"10.1021\/acs.jmedchem.9b00444","article-title":"Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165","volume":"62","author":"Stephen","year":"2019","journal-title":"J Med Chem."},{"issue":"2","key":"10.1016\/j.bmcl.2022.128728_b0035","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1016\/S2352-3026(17)30237-5","article-title":"Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial","volume":"5","author":"Harrison","year":"2018","journal-title":"Lancet Haematol."},{"issue":"12","key":"10.1016\/j.bmcl.2022.128728_b0040","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1016\/j.jid.2020.03.962","article-title":"TYK2\/JAK1 Inhibitor PF-06700841 in Patients with Plaque Psoriasis: Phase IIa, Randomized, Double-Blind, Placebo-Controlled Trial","volume":"140","author":"Forman","year":"2020","journal-title":"J Invest Dermatol."},{"key":"10.1016\/j.bmcl.2022.128728_b0045","doi-asserted-by":"crossref","first-page":"104609","DOI":"10.1016\/j.phrs.2019.104609","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update","volume":"152","author":"Roskoski","year":"2020","journal-title":"Pharmacol Res."},{"key":"10.1016\/j.bmcl.2022.128728_b0050","author":"Thombare","year":"2013","journal-title":"Heterocyclic compounds"},{"key":"10.1016\/j.bmcl.2022.128728_b0055","unstructured":"Ranjit D, Jigar D, Pankaj P. N-Cyanomethylamide as inhibitor janus kinase. 2015; PCT application, WO2015054351."},{"key":"10.1016\/j.bmcl.2022.128728_b0060","doi-asserted-by":"crossref","first-page":"103851","DOI":"10.1016\/j.bioorg.2020.103851","volume":"99","author":"Rajesh","year":"2020","journal-title":"Bioorg Chem."},{"issue":"20","key":"10.1016\/j.bmcl.2022.128728_b0065","doi-asserted-by":"crossref","first-page":"5887","DOI":"10.1016\/j.bmcl.2009.08.071","article-title":"Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs)","volume":"19","author":"Burns","year":"2009","journal-title":"Bioorg Med Chem Lett."},{"key":"10.1016\/j.bmcl.2022.128728_b0070","unstructured":"Schr\u00f6dinger Release 2018-4: Glide, Schr\u00f6dinger, LLC, New York, NY, 2018."},{"key":"10.1016\/j.bmcl.2022.128728_b0075","first-page":"141","article-title":"Scaffold Flatness: Reversing the Trend","volume":"1","author":"Fatemeh","year":"2013","journal-title":"Sci Rev."},{"issue":"21","key":"10.1016\/j.bmcl.2022.128728_b0080","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1021\/jm901241e","article-title":"Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success","volume":"52","author":"Lovering","year":"2009","journal-title":"J Med Chem."},{"key":"10.1016\/j.bmcl.2022.128728_b0085","unstructured":"Cochran J, Green J, Hale MR, Ledford B, Maltais F, Nanthakumar S. Protein kinase inhibitors and use thereof. 2004, PCT application, WO2004016597."},{"key":"10.1016\/j.bmcl.2022.128728_b0090","unstructured":"Ranjit D, Jigar D, Patel P. N-Cyanomethylamide as inhibitors of Janus kinase. 2015, PCT application, WO2015019365."},{"key":"10.1016\/j.bmcl.2022.128728_b0095","unstructured":"N-(cyanomethyl)-4-(5-fluoro-2-((4-(4-morpholinopiperidin-1- l)phenyl)amino)pyrimidin-4- yl)benzamide (32). Yellow color solid ; Mp: 235\u00b0C. IR (KBr): \u03bd = 3412\u03bd(N-H), 3360v(N-H), 2251\u03bd(CN), 1662 \u03bd(C=O), 1599\u03bd (CH2), 1531\u03bd (CH2), 1444 \u03bd (CH2); 1H NMR (400 MHz, d6-DMSO): \u03b4 = 9.30 (t, 2H, J = 5.2 Hz), 8.36 (s, 1H), 7.98 (d, 2H, J = 8.4 Hz), 7.77 (d, 2H, J = 8.0 Hz), 7.57 (d, 2H, J = 8.8 Hz), 6.85 (d, 2H, J = 8.8 Hz), 4.34 (d, 2H, J = 5.6 Hz), 3.57- 3.60 (m, 6H), 2.54-2.59 (m, 2H), 2.19 (s, 3H), 1.82-1.85 (m, 2H), 1.47-1.49 (m, 2H). 13C NMR and DEPT (100 MHz, DMSO-d6): \u03b4 = 166.57 (CO), 157.33 (C), 151.55 (C), 146.87 (C), 136.91 (C), 135.03 (C), 132.79 (C), 129.19 (CH), 128.24 (CH), 120.56 (CH), 118.05 (CN), 116.83 (CH), 67.01 (CH2), 61.59 (C), 49.35 (CH2), 49.07 (CH2), 28.29 (CH2), 28.20 (CH2). ESI-Q- TOF-MS: m\/z [M+H]+ calcd for [C28H30FN7O2]+: 515.5; found: 516.20; Purity: 97.99% (UPLC)."},{"issue":"2","key":"10.1016\/j.bmcl.2022.128728_b0100","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3390\/pharmaceutics11020070","article-title":"Applicability of a modified rat model of acute arthritis for long-term testing of drug delivery systems","volume":"11","author":"Rudnik-Jansen","year":"2019","journal-title":"Pharmaceutics"}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X22002049?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X22002049?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:44:37Z","timestamp":1760773477000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X22002049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":20,"alternative-id":["S0960894X22002049"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2022.128728","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Optimisation of momelotinib with improved potency and efficacy as pan-JAK inhibitor","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2022.128728","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"128728"}}