Rupintrivir

Rupintrivir
Clinical data
Trade names	Rupintrivir
Legal status
Legal status	US: Investigational drug;
Identifiers
	IUPAC name Ethyl (E,4S)-4-[[(2R,5S)-2-[(4-fluorophenyl)methyl]-6-methyl-5-[(5-methyl-1,2-oxazole-3-carbonyl)amino]-4-oxoheptanoyl]amino]-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate;
CAS Number	223537-30-2;
PubChem CID	6440352;
DrugBank	05102;
ChemSpider	4944627;
UNII	RGE5K1Q5QW;
KEGG	D05776;
ChEMBL	ChEMBL20210;
Chemical and physical data
Formula	C31H39FN4O7
Molar mass	598.672 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCOC(=O)/C=C/[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC2=CC=C(C=C2)F)CC(=O)[C@H](C(C)C)NC(=O)C3=NOC(=C3)C;
	InChI InChI=1S/C31H39FN4O7/c1-5-42-27(38)11-10-24(16-21-12-13-33-29(21)39)34-30(40)22(15-20-6-8-23(32)9-7-20)17-26(37)28(18(2)3)35-31(41)25-14-19(4)43-36-25/h6-11,14,18,21-22,24,28H,5,12-13,15-17H2,1-4H3,(H,33,39)(H,34,40)(H,35,41)/b11-10 /t21-,22 ,24 ,28-/m0/s1; Key:CAYJBRBGZBCZKO-BHGBQCOSSA-N;

Rupintrivir (AG-7088, Rupinavir) is a peptidomimetic antiviral drug which acts as a 3C and 3CL protease inhibitor.^[1]^[2]^[3] It was developed for the treatment of rhinoviruses,^[4]^[5] and has subsequently been investigated for the treatment of other viral diseases including those caused by picornaviruses,^[6]^[7] norovirus,^[8] and coronaviruses, such as SARS and COVID-19.^[9]^[10]

References

^ Dragovich PS, Prins TJ, Zhou R, Webber SE, Marakovits JT, Fuhrman SA, et al. (April 1999). "Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements". Journal of Medicinal Chemistry. 42 (7): 1213–24. doi:10.1021/jm9805384. PMID 10197965.
^ Santos MM, Moreira R (October 2007). "Michael acceptors as cysteine protease inhibitors". Mini Reviews in Medicinal Chemistry. 7 (10): 1040–50. doi:10.2174/138955707782110105. PMID 17979807.
^ Yuan S, Fan K, Chen Z, Sun Y, Hou H, Zhu L (February 2020). "Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design". Virologica Sinica. 35 (4): 445–454. doi:10.1007/s12250-020-00196-4. PMC 7462945. PMID 32103448.
^ Patick AK, Binford SL, Brothers MA, Jackson RL, Ford CE, Diem MD, et al. (October 1999). "In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease". Antimicrobial Agents and Chemotherapy. 43 (10): 2444–50. doi:10.1128/AAC.43.10.2444. PMC 89498. PMID 10508022.
^ Jensen LM, Walker EJ, Jans DA, Ghildyal R (2015). "Proteases of human rhinovirus: role in infection". Rhinoviruses. Methods in Molecular Biology. Vol. 1221. pp. 129–41. doi:10.1007/978-1-4939-1571-2_10. ISBN 978-1-4939-1570-5. PMID 25261311.
^ Barnard DL (2006). "Current status of anti-picornavirus therapies". Current Pharmaceutical Design. 12 (11): 1379–90. doi:10.2174/138161206776361129. PMID 16611122.
^ De Palma AM, Vliegen I, De Clercq E, Neyts J (November 2008). "Selective inhibitors of picornavirus replication". Medicinal Research Reviews. 28 (6): 823–84. doi:10.1002/med.20125. PMID 18381747. S2CID 1575335.
^ Rocha-Pereira J, Nascimento MS, Ma Q, Hilgenfeld R, Neyts J, Jochmans D (August 2014). "The enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti-norovirus activity and clears cells from the norovirus replicon". Antimicrobial Agents and Chemotherapy. 58 (8): 4675–81. doi:10.1128/AAC.02546-13. PMC 4136040. PMID 24890597.
^ Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R (June 2003). "Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs". Science. 300 (5626): 1763–7. Bibcode:2003Sci...300.1763A. doi:10.1126/science.1085658. PMID 12746549.
^ Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, et al. (2020). "Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases". ACS Central Science. 6 (3): 315–331. doi:10.1021/acscentsci.0c00272. PMC 7094090. PMID 32226821.

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[1] Dragovich PS, Prins TJ, Zhou R, Webber SE, Marakovits JT, Fuhrman SA, et al. (April 1999). "Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements". Journal of Medicinal Chemistry. 42 (7): 1213–24. doi:10.1021/jm9805384. PMID 10197965.

[2] Santos MM, Moreira R (October 2007). "Michael acceptors as cysteine protease inhibitors". Mini Reviews in Medicinal Chemistry. 7 (10): 1040–50. doi:10.2174/138955707782110105. PMID 17979807.

[3] Yuan S, Fan K, Chen Z, Sun Y, Hou H, Zhu L (February 2020). "Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design". Virologica Sinica. 35 (4): 445–454. doi:10.1007/s12250-020-00196-4. PMC 7462945. PMID 32103448.

[4] Patick AK, Binford SL, Brothers MA, Jackson RL, Ford CE, Diem MD, et al. (October 1999). "In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease". Antimicrobial Agents and Chemotherapy. 43 (10): 2444–50. doi:10.1128/AAC.43.10.2444. PMC 89498. PMID 10508022.

[5] Jensen LM, Walker EJ, Jans DA, Ghildyal R (2015). "Proteases of human rhinovirus: role in infection". Rhinoviruses. Methods in Molecular Biology. Vol. 1221. pp. 129–41. doi:10.1007/978-1-4939-1571-2_10. ISBN 978-1-4939-1570-5. PMID 25261311.

[6] Barnard DL (2006). "Current status of anti-picornavirus therapies". Current Pharmaceutical Design. 12 (11): 1379–90. doi:10.2174/138161206776361129. PMID 16611122.

[7] De Palma AM, Vliegen I, De Clercq E, Neyts J (November 2008). "Selective inhibitors of picornavirus replication". Medicinal Research Reviews. 28 (6): 823–84. doi:10.1002/med.20125. PMID 18381747. S2CID 1575335.

[8] Rocha-Pereira J, Nascimento MS, Ma Q, Hilgenfeld R, Neyts J, Jochmans D (August 2014). "The enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti-norovirus activity and clears cells from the norovirus replicon". Antimicrobial Agents and Chemotherapy. 58 (8): 4675–81. doi:10.1128/AAC.02546-13. PMC 4136040. PMID 24890597.

[9] Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R (June 2003). "Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs". Science. 300 (5626): 1763–7. Bibcode:2003Sci...300.1763A. doi:10.1126/science.1085658. PMID 12746549.

[10] Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, et al. (2020). "Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases". ACS Central Science. 6 (3): 315–331. doi:10.1021/acscentsci.0c00272. PMC 7094090. PMID 32226821.

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See also

References