盧夫特韋(英語:Lufotrelvir、PF-07304814)是輝瑞公司開發的一種抗病毒藥物,可作為3CL蛋白酶抑制劑[1]它是一種前體藥物,其磷酸基團在體內被裂解以產生活性劑PF-00835231[2]盧夫特韋正在用於治療COVID-19的人體臨床試驗中,並顯示出對COVID-19的良好活性,包括幾種變異株,但與相關藥物奈瑪特韋不同,它沒有口服活性,必須通過靜脈注射給藥,因此一直總體而言,臨床開發中不太受歡迎的候選者。[3][4][5]

盧夫特韋
法律規範狀態
法律規範
  • Investigational drug
識別資訊
  • [(3S)-3-[(2S)-2-[(4-methoxy-1H-indol-2-yl)formamido]-4-methylpentanamido]-2-oxo-4-[(3S)-2-oxopyrrolidin-3-yl]butoxy]phosphonic acid
CAS號2468015-78-1
PubChem CID
DrugBank
UNII
KEGG
ChEBI
CompTox Dashboard英語CompTox Chemicals Dashboard (EPA)
化學資訊
化學式C24H33N4O9P
摩爾質量552.52 g·mol−1
3D模型(JSmol英語JSmol
  • CC(C)C[C@@H](C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(=O)COP(=O)(O)O)NC(=O)C2=CC3=C(N2)C=CC=C3OC
  • InChI=1S/C24H33N4O9P/c1-13(2)9-18(28-24(32)19-11-15-16(26-19)5-4-6-21(15)36-3)23(31)27-17(10-14-7-8-25-22(14)30)20(29)12-37-38(33,34)35/h4-6,11,13-14,17-18,26H,7-10,12H2,1-3H3,(H,25,30)(H,27,31)(H,28,32)(H2,33,34,35)/t14-,17-,18-/m0/s1
  • Key:FQKALOFOWPDTED-WBAXXEDZSA-N

參見

編輯

參考文獻

編輯
  1. ^ Hoffman RL, Kania RS, Brothers MA, Davies JF, Ferre RA, Gajiwala KS, et al. Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19. Journal of Medicinal Chemistry. November 2020, 63 (21): 12725–12747. PMC 7571312 . PMID 33054210. doi:10.1021/acs.jmedchem.0c01063. 
  2. ^ Boras, Britton; Jones, Rhys M.; Anson, Brandon J.; Arenson, Dan; Aschenbrenner, Lisa; Bakowski, Malina A.; Beutler, Nathan; Binder, Joseph; Chen, Emily; Eng, Heather; Hammond, Holly. Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19. Nature Communications. 2021-10-18, 12 (1): 6055. Bibcode:2021NatCo..12.6055B. ISSN 2041-1723. PMC 8523698 . PMID 34663813. doi:10.1038/s41467-021-26239-2 (英語). 
  3. ^ de Vries M, Mohamed AS, Prescott RA, Valero-Jimenez AM, Desvignes L, O'Connor R, et al. A comparative analysis of SARS-CoV-2 antivirals characterizes 3CLpro inhibitor PF-00835231 as a potential new treatment for COVID-19. Journal of Virology. February 2021, 95 (10). PMC 8139662 . PMID 33622961. doi:10.1128/JVI.01819-20. 
  4. ^ Baig MH, Sharma T, Ahmad I, Abohashrh M, Alam MM, Dong JJ. Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study. Molecules. March 2021, 26 (6): 1678. PMC 8002701 . PMID 33802860. doi:10.3390/molecules26061678 . 
  5. ^ Vandyck K, Deval J. Considerations for the discovery and development of 3-chymotrypsin-like cysteine protease inhibitors targeting SARS-CoV-2 infection. Current Opinion in Virology. August 2021, 49: 36–40. PMC 8075814 . PMID 34029993. doi:10.1016/j.coviro.2021.04.006.