PF-07321332

PF-07321332 is an orally bioavailable inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), also known as 3C-like protease (3CLpro), with a Ki value of 3.11 nM. It also inhibits Mpro from other members of the Betacoronavirus genus, including SARS-CoV-1, HKU1-CoV, OC43-CoV, and MERS-CoV (Kis = 4.94, 189, 36.4, and 187 nM, respectively), as well as Mpro from NL-63-CoV and 229E CoV (Kis = 226 and 44.4 nM, respectively), which are members of the Alphacoronavirus genus. PF-07321332 is selective for these enzymes over several other proteases, including human and HIV-1 proteases (IC50s = >100 µM for all), as well as a panel of G protein-coupled receptors, kinases, and transporters (IC50s = >100 µM for all). It inhibits SARS-CoV-2 replication in A549 cells (EC50 = 77.9 nM) and reduces the cytopathic effect of SARS-CoV-2 in infected Vero E6 cells (EC50 = 74.5 nM) with a 50% cytotoxic concentration (CC50) value of greater than 100 µM. PF-07321332 (300 and 1,000 mg/kg) reduces lung viral titers and the severity of pulmonary lesions in mice infected with the mouse-adapted SARS-CoV-2 MA10 variant. Formulations containing PF-07321332 have been used in the treatment of COVID-19.Formal Name: (1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxo-3-pyrrolidinyl]ethyl]-3-[(2S)-3,3-dimethyl-1-oxo-2-[(2,2,2-trifluoroacetyl)amino]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide. CAS Number: 2628280-40-8. Synonyms: Nirmatrelvir. Molecular Formula: C23H32F3N5O4. Formula Weight: 499.5. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMF: 2 mg/ml, DMSO: 5 mg/ml, Ethanol: 15 mg/ml, PBS (pH 7.2): insol. SMILES: FC(F)(F)C(N[C@@H](C(C)(C)C)C(N1C[C@@](C2(C)C)([H])[C@@]2([H])[C@H]1C(N[C@H](C#N)C[C@H]3C(NCC3)=O)=O)=O)=O. InChi Code: InChI=1S/C23H32F3N5O4/c1-21(2,3)16(30-20(35)23(24,25)26)19(34)31-10-13-14(22(13,4)5)15(31)18(33)29-12(9-27)8-11-6-7-28-17(11)32/h11-16H,6-8,10H2,1-5H3,(H,28,32)(H,29,33)(H,30,35)/t11-,12-,13-,14-,15-,16+/m0/s1. InChi Key: LIENCHBZNNMNKG-OJFNHCPVSA-N.