nirmatrelvir   Click here for help

GtoPdb Ligand ID: 11503

Synonyms: example E61 [WO2021250648A1] | Paxlovid® (nirmatrelvir + ritonavir) | PF-07321332 | PF07321332
Approved drug
nirmatrelvir is an approved drug (UK MHRA (2021), EMA (2022))
Compound class: Synthetic organic
Comment: PF-07321332 (nirmatrelvir) is an oral antiviral clinical lead. It is a covalent inhibitor of SARS-CoV-2 Mpro (main protease, 3CLpro) that binds to cysteine145 within the enzyme's catalytic domain [4]. Mpro is essential for coronavirus replication. Inhibiting Mpro actvity blocks replication at an early stage in the virus' life cycle. Due to structural similarities between the Mpro's of other coronavirusus, PF-07321332 offers the potential of pan-coronavirus activity. In vitro it is suggested to inhibit replication of CoV-2 variants including delta and omicron.

PF-07321332 is structurally similar to ML1000. Prior to peer-reviewed name-to-structure disclosure, we obtained the structure represented here from an online report by Dr Bethany Halford who attended a session by Dafydd Owen (Pfizer) at the ACS Spring 2021 meeting (@beth_halford image on Twitter) which rendered the SMILES string N#C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H]1N(C[C@H]2[C@@H]1C2(C)C)C(=O)[C@H](C(C)(C)C)NC(=O)C(F)(F)F. PF-07321332's chemical structure was formally disclosed in Owen et al's Science article in November 2021 [3], and this confirmed the structure that was obtained from the ACS meeting.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 131.4
Molecular weight 499.24
XLogP 1.39
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES N#C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H]1N(C[C@H]2[C@@H]1C2(C)C)C(=O)[C@H](C(C)(C)C)NC(=O)C(F)(F)F
Isomeric SMILES N#C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H]1N(C[C@H]2[C@@H]1C2(C)C)C(=O)[C@H](C(C)(C)C)NC(=O)C(F)(F)F
InChI 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
References
1. Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, Baniecki M, Hendrick VM, Damle B, Simón-Campos A et al.. (2022)
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.
N Engl J Med, [Epub ahead of print]. DOI: 10.1056/NEJMoa2118542 [PMID:35172054]
2. Luttens A, Gullberg H, Abdurakhmanov E, Vo DD, Akaberi D, Talibov VO, Nekhotiaeva N, Vangeel L, De Jonghe S, Jochmans D et al.. (2022)
Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses.
J Am Chem Soc, [Epub ahead of print]. DOI: 10.1021/jacs.1c08402 [PMID:35142215]
3. Owen DR, Allerton CMN, Anderson AS, Aschenbrenner L, Avery M, Berritt S, Boras B, Cardin RD, Carlo A, Coffman KJ et al.. (2021)
An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19.
Science, 374 (6575): 1586-1593. [PMID:34726479]
4. Owen DR, Pettersson MY, Reese MR, Sammons MF, Tuttle JB, Verhoest PR, Wei L, Yang Q, Yang X. (2021)
Nitrile-containing antiviral compounds.
Patent number: WO2021250648A1. Assignee: Pfizer Inc.. Priority date: 03/09/2021. Publication date: 16/12/2021.