دورية أكاديمية
SAR studies of 4-acyl-1,6-dialkylpiperazin-2-one arenavirus cell entry inhibitors.
| العنوان: | SAR studies of 4-acyl-1,6-dialkylpiperazin-2-one arenavirus cell entry inhibitors. |
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| المؤلفون: | Plewe MB; Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92054, United States., Whitby LR; Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States., Naik S; Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92054, United States., Brown ER; Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92054, United States., Sokolova NV; Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92054, United States., Gantla VR; Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92054, United States., York J; Montana Biotechnology Center, The University of Montana, Missoula, MT 59812, United States., Nunberg JH; Montana Biotechnology Center, The University of Montana, Missoula, MT 59812, United States., Zhang L; Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, United States., Kalveram B; Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, United States., Freiberg AN; Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, United States; Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, TX 77555, United States., Boger DL; Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States., Henkel G; Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92054, United States., McCormack K; Arisan Therapeutics, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92054, United States. Electronic address: kenm@arisanthera.com. |
| المصدر: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Nov 15; Vol. 29 (22), pp. 126620. Date of Electronic Publication: 2019 Aug 24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9107377 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3405 (Electronic) Linking ISSN: 0960894X NLM ISO Abbreviation: Bioorg Med Chem Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1991- |
| مواضيع طبية MeSH: | Antiviral Agents/*pharmacology , Arenavirus/*drug effects , Piperazines/*pharmacology , Viral Envelope Proteins/*antagonists & inhibitors, Antiviral Agents/chemical synthesis ; Antiviral Agents/chemistry ; Arenavirus/metabolism ; Dose-Response Relationship, Drug ; Microbial Sensitivity Tests ; Molecular Structure ; Piperazines/chemical synthesis ; Piperazines/chemistry ; Structure-Activity Relationship ; Viral Envelope Proteins/metabolism |
| مستخلص: | Old World (Africa) and New World (South America) arenaviruses are associated with human hemorrhagic fevers. Efforts to develop small molecule therapeutics have yielded several chemical series including the 4-acyl-1,6-dialkylpiperazin-2-ones. Herein, we describe an extensive exploration of this chemotype. In initial Phase I studies, R 1 and R 4 scanning libraries were assayed to identify potent substituents against Old World (Lassa) virus. In subsequent Phase II studies, R 6 substituents and iterative R 1 , R 4 and R 6 substituent combinations were evaluated to obtain compounds with improved Lassa and New World (Machupo, Junin, and Tacaribe) arenavirus inhibitory activity, in vitro human liver microsome metabolic stability and aqueous solubility. (Copyright © 2019 Elsevier Ltd. All rights reserved.) |
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| معلومات مُعتمدة: | R44 AI112097 United States AI NIAID NIH HHS; R43 AI112097 United States AI NIAID NIH HHS; R01 CA042056 United States CA NCI NIH HHS; R01 AI074818 United States AI NIAID NIH HHS; U54 AI065357 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: Arenavirus; Entry inhibitor; Junin; Lassa; Machupo; Piperazinone |
| المشرفين على المادة: | 0 (Antiviral Agents) 0 (Piperazines) 0 (Viral Envelope Proteins) |
| تواريخ الأحداث: | Date Created: 20190921 Date Completed: 20201022 Latest Revision: 20231014 |
| رمز التحديث: | 20231014 |
| مُعرف محوري في PubMed: | PMC6803051 |
| DOI: | 10.1016/j.bmcl.2019.08.024 |
| PMID: | 31537423 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1464-3405 |
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| DOI: | 10.1016/j.bmcl.2019.08.024 |