Nirmatrelvir MTBE Solvate

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H32F3N5O4.C5H12O
Molecular Weight	587.6747
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(C)(C)C.CC(C)(C)[C@H](NC(=O)C(F)(F)F)C(=O)N1C[C@H]2[C@@H]([C@H]1C(=O)N[C@@H](C[C@@H]3CCNC3=O)C#N)C2(C)C

InChI

InChIKey=DDJIAJAROZGFHS-PHOKCBTLSA-N

InChI=1S/C23H32F3N5O4.C5H12O/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;1-5(2,3)6-4/h11-16H,6-8,10H2,1-5H3,(H,28,32)(H,29,33)(H,30,35);1-4H3/t11-,12-,13-,14-,15-,16+;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C5H12O
Molecular Weight	88.1482
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C23H32F3N5O4
Molecular Weight	499.5265
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/35845944/

Nirmatrelvir (PF-07321332) is a new oral antiviral drug developed by Pfizer. Nirmatrelvir is a major bioavailable oral SARS-CoV-2 protease inhibitor with in vitro human coronavirus antiviral activity, and excellent selection of off-target and in vivo immune profiles. The combination of ritonavir and nirmatrelvir under the brand name Paxlovid was approved by the FDA on May 25, 2023, for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro), also referred to as 3C-like protease (3CLpro) or nonstructural protein 5 (nsp5) protease. Inhibition of SARS-CoV-2 Mpro renders it incapable of processing the viral polyproteins pp1a and pp1ab, preventing viral replication. Nirmatrelvir inhibited the activity of recombinant SARS-CoV-2 Mpro in a biochemical assay with a Ki value of 3.1 nM and an IC50 value of 19.2 nM. Nirmatrelvir was found to bind directly to the SARS-CoV-2 Mpro active site by X-ray crystallography.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Replicase polyprotein 1ab 2 Target ID: CHEMBL5118 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf\|https://pubmed.ncbi.nlm.nih.gov/36503248	Inhibitor 8504		3.1 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
COVID-19 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf	Primary		Approved 8583	PAXLOVID Approved Use PAXLOVID is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. Launch Date 2023

C_max

Value	Dose	Co-administered	Analyte	Population
1.6 μg/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.08 μg/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.21 μg/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.37 μg/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
14.46 μg × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17.91 μg × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
27.11 μg × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
44.04 μg × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.73 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.61 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.95 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.37 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.2688	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	NIRMATRELVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Analyte	Population
0.296% EXPERIMENT https://dmd.aspetjournals.org/content/dmd/50/5/576.full.pdf?with-ds=yes	0.3 μmol 1 times / day steady-state, unknown dose: 0.3 μmol route of administration: UNKNOWN experiment type: STEADY-STATE co-administered:	NIRMATRELVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.3% EXPERIMENT https://dmd.aspetjournals.org/content/dmd/50/5/576.full.pdf?with-ds=yes	1 μmol 1 times / day steady-state, unknown dose: 1 μmol route of administration: UNKNOWN experiment type: STEADY-STATE co-administered:	NIRMATRELVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.311% EXPERIMENT https://dmd.aspetjournals.org/content/dmd/50/5/576.full.pdf?with-ds=yes	3 μmol 1 times / day steady-state, unknown dose: 3 μmol route of administration: UNKNOWN experiment type: STEADY-STATE co-administered:	NIRMATRELVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.333% EXPERIMENT https://dmd.aspetjournals.org/content/dmd/50/5/576.full.pdf?with-ds=yes	10 μmol 1 times / day steady-state, unknown dose: 10 μmol route of administration: UNKNOWN experiment type: STEADY-STATE co-administered:	NIRMATRELVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438 inducer 440	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153 CYP2C8 1057 CYP2B6 926 Nav1.5 116 OCT1 620 Cav1.2 58 CYP3A5 136 P-gp 1741 MATE1 415	OAT3 391 OCT1 393 PEPT1 60 OATP1B1 503 CYP3A 220 P-gp 2052 MATE1 182 BCRP 697 MATE2K 6 NTCP 22 OAT1 395 OAT2 125 OCT2 434 OATP1B3 435 OATP2B1 122 OATP4C1 2	CYP2B6 669 CYP2C8 198

Drug as perpetrator

Target	Modality	Activity
MATE1 416	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/paxlovid-epar-public-assessment-report_en.pdf Page: 69.0	likely
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	no
CYP3A5 201	inhibitor 4027 Sources: https://mhraproducts4853.blob.core.windows.net/docs/2592340a78dc1cc5b892ac54dc66da76f7a8e1e1 Page: 16.0	no
OCT1 656	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/paxlovid-epar-public-assessment-report_en.pdf Page: 69.0	yes [IC50 138.1 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf \| https://www.ema.europa.eu/en/documents/assessment-report/paxlovid-epar-public-assessment-report_en.pdf#page=69 Page: 25.0	yes [IC50 70.6 uM]
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	yes
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	yes
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	yes
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 24.0	yes
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf \| https://mhraproducts4853.blob.core.windows.net/docs/2592340a78dc1cc5b892ac54dc66da76f7a8e1e1#page=16 Page: 24.0	yes

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
MATE2K 6	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
NTCP 22	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OAT1 395	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OAT2 125	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OAT3 391	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OATP2B1 122	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OATP4C1 2	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
PEPT1 60	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	no
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 8.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf Page: 25.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	inhibitor 2237 Sources: https://www.ema.europa.eu/en/documents/assessment-report/paxlovid-epar-public-assessment-report_en.pdf Page: 40.0
Nav1.5 119	inhibitor 2237 Sources: https://www.ema.europa.eu/en/documents/assessment-report/paxlovid-epar-public-assessment-report_en.pdf Page: 40.0
hERG 2263	inhibitor 2237 Sources: https://mhraproducts4853.blob.core.windows.net/docs/2592340a78dc1cc5b892ac54dc66da76f7a8e1e1 Page: 14.0

PubMed

Title	Date	PubMed
VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19.	2023-02-02	36577095
Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs.	2023-01-06	35245942
Recommendations for the Management of Drug-Drug Interactions Between the COVID-19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications.	2022-12	35567754
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.	2022-04-14	35172054
Nirmatrelvir Plus Ritonavir: First Approval.	2022-04	35305258

Patents

Sample Use Guides

In Vivo Use Guide

Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all 3 tablets taken together twice daily for 5 days.

Route of Administration: Oral

In Vitro Use Guide

Nirmatrelvir inhibited the activity of recombinant SARS-CoV-2 Mpro in a biochemical assay with a Ki value of 3.1 nM and an IC50 value of 19.2 nM.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 15:35:07 GMT 2025` Edited by `admin` on `Wed Apr 02 15:35:07 GMT 2025`
Record UNII	38642DG4UE
Record Status	`Validated (UNII)`
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Name

Type

Language

Nirmatrelvir MTBE Solvate

Common Name

English

PF-07321332 MTBE Solvate

Preferred Name

English

3-Azabicyclo[3.1.0]hexane-2-carboxamide, 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-, compd. with 2-methoxy-2-methylpropane (1:1), (1R,2S,5S)-

Systematic Name

English

Code System Code Type Description

CAS

2755812-44-1

Created by admin on Wed Apr 02 15:35:07 GMT 2025 , Edited by admin on Wed Apr 02 15:35:07 GMT 2025

PRIMARY

FDA UNII

38642DG4UE

Created by admin on Wed Apr 02 15:35:07 GMT 2025 , Edited by admin on Wed Apr 02 15:35:07 GMT 2025

PRIMARY

PUBCHEM

164971185

Created by admin on Wed Apr 02 15:35:07 GMT 2025 , Edited by admin on Wed Apr 02 15:35:07 GMT 2025

PRIMARY

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ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/35845944/

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217188s000lbl.pdf|https://pubmed.ncbi.nlm.nih.gov/35845944/

C_max

T_1/2

F_unbound

Drug as perpetrator