RUPINTRIVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H39FN4O7
Molecular Weight	598.6624
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)\C=C\[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@@H](CC(=O)[C@@H](NC(=O)C2=NOC(C)=C2)C(C)C)CC3=CC=C(F)C=C3

InChI

InChIKey=CAYJBRBGZBCZKO-BHGBQCOSSA-N

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

HIDE SMILES / InChI

Molecular Formula	C31H39FN4O7
Molecular Weight	598.6624
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11249711 | https://www.ncbi.nlm.nih.gov/pubmed/14638501 | https://www.ncbi.nlm.nih.gov/pubmed/24890597 | https://www.ncbi.nlm.nih.gov/pubmed/23295352

Rupintrivir is a peptide aldehyde that targets the human rhinovirus (HRV) 3C proteinase enzyme and has the potential for the treatment of the common cold. Rupintrivir is derived from AG-6084 - in order to develop human rhinovirus 3C protease inhibitors with improved pharmacological properties, Agouron replaced the backbone amide moiety of the series which yielded AG-6084, with a ketomethylene isostere. A phase II efficacy study has been completed in healthy patients infected with the rhinovirus. Ruprintrivir was well tolerated; blood-tinged mucus and nasal passage irritation were the most common adverse effects reported. Pharmacokinetic analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug residence with minimal systemic absorption. The fact that rupintrivir is active against noroviruses belonging to genogroup I (Norwalk virus), genogroup V (murine norovirus), and the recombinant 3C-like protease of a GII norovirus suggests that the drug exerts cross-genotypic anti-norovirus activity and will thus most likely be effective against the clinically relevant human norovirus strains. Rupintrivir is also a high affinity inhibitor of Enterovirus-71 3C protease.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
HRV-14 3C protease 1 Target ID: HRV-14 3C protease Sources: https://www.ncbi.nlm.nih.gov/pubmed/10197965 \| https://www.ncbi.nlm.nih.gov/pubmed/10508022	Inhibitor 8504	0.005 µM [EC50]
EV-A71 3C protease 1 Target ID: EV-A71 3C protease Sources: https://www.ncbi.nlm.nih.gov/pubmed/27668727 \| https://www.ncbi.nlm.nih.gov/pubmed/27645381	Inhibitor 8504	7.3 µM [IC50]
GII norovirus 3C-like protease 1 Target ID: GII norovirus 3C-like protease Sources: https://www.ncbi.nlm.nih.gov/pubmed/24890597	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Rhinovirus cold 2 Sources: http://adisinsight.springer.com/drugs/800010377 https://www.ncbi.nlm.nih.gov/pubmed/14638501	Primary	Phase II 1147	Unknown Approved Use Unknown
Hand foot and mouth disease 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27645381 https://www.ncbi.nlm.nih.gov/pubmed/27668727	Primary	Preclinical	Unknown Approved Use Unknown
Norovirus infections 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24890597	Primary	Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
0.46 ng/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	4 mg single, nasal dose: 4 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.75 ng/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	8 mg single, nasal dose: 8 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.44 ng/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	4 mg single, nasal dose: 4 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.46 ng/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	4 mg 1 times / day multiple, nasal dose: 4 mg route of administration: Nasal experiment type: MULTIPLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.67 ng/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	8 mg single, nasal dose: 8 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.18 ng/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	8 mg 1 times / day multiple, nasal dose: 8 mg route of administration: Nasal experiment type: MULTIPLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
5.94 ng × h/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	4 mg single, nasal dose: 4 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
10.09 ng × h/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	8 mg single, nasal dose: 8 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.58 ng × h/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	4 mg single, nasal dose: 4 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.46 ng × h/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	4 mg 1 times / day multiple, nasal dose: 4 mg route of administration: Nasal experiment type: MULTIPLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.3 ng × h/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	8 mg single, nasal dose: 8 mg route of administration: Nasal experiment type: SINGLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.48 ng × h/mL CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	8 mg 1 times / day multiple, nasal dose: 8 mg route of administration: Nasal experiment type: MULTIPLE co-administered:	RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.54 h CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	4 mg single, nasal dose: 4 mg route of administration: Nasal experiment type: SINGLE co-administered:		RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.77 h CLINICAL TRIAL https://journals.asm.org/doi/10.1128/aac.46.2.392-397.2002#T3	8 mg single, nasal dose: 8 mg route of administration: Nasal experiment type: SINGLE co-administered:		RUPINTRIVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
Axon MedChem	1571	https://www.axonmedchem.com/product/1571
BOC Sciences	223537-30-2	http://www.bocsci.com/description.asp?cas=223537-30-2
Chem Scene	CS-0025036	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0025036
Compound Cloud	6440352
eMolecules	207350898	https://orderbb.emolecules.com/search/#?query=207350898
Innovapharm	VT-00686288
mcule	MCULE-1649906808	https://mcule.com/MCULE-1649906808/
mcule	MCULE-3885677075	https://mcule.com/MCULE-3885677075/
MedChem Express	HY-106161	https://www.medchemexpress.com/search.html?q=HY-106161&ft=&fa=&fp=
Molnova	M13584	https://www.molnova.com/en/serch-list.html?keywords=M13584
MolPort	MolPort-006-170-056	https://www.molport.com/shop/molecule-link/MolPort-006-170-056
Toronto Research Chemicals	R701700	https://www.trc-canada.com/product-detail/?CatNum=R701700
Toronto Research Chemicals	R701702	https://www.trc-canada.com/product-detail/?CatNum=R701702

PubMed

Title	Date	PubMed
In vitro resistance study of rupintrivir, a novel inhibitor of human rhinovirus 3C protease.	2007-12	17908951
Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors.	2005-11-03	16250632
Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic alpha,beta-unsaturated esters.	2005-09-01	15994085
Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhinovirus 3C protease inhibitor.	2005-02	15673742
Structural variations in keto-glutamines for improved inhibition against hepatitis A virus 3C proteinase.	2004-07-16	15203137
Pharmacokinetics and safety of an antirhinoviral agent, ruprintrivir, in healthy volunteers.	2002-02	11796347
Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors.	2001-10-22	11591501
In vitro activity of pleconaril and AG7088 against selected serotypes and clinical isolates of human rhinoviruses.	2000-09	10974374
Inhibition of human rhinovirus-induced cytokine production by AG7088, a human rhinovirus 3C protease inhibitor.	2000-05	10770757
In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease.	1999-10	10508022
Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes.	1999-09-28	10500114
Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements.	1999-04-08	10197965

Patents

Sample Use Guides

In Vivo Use Guide

8 mg two or five times daily for 5 days.

Route of Administration: Nasal

In Vitro Use Guide

In H1-HeLa or MRC-5 cell protection assays, AG7088 was active against all four picornaviruses tested (CAV 21, CVB 3, EV 11, ETV 70), with EC50 ranging from 0.007 to 0.183 uM and EC90 ranging from 0.033 to 0.340 uM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:27:20 GMT 2025` Edited by `admin` on `Mon Mar 31 18:27:20 GMT 2025`
Record UNII	RGE5K1Q5QW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AG-7088

Preferred Name

English

RUPINTRIVIR

Official Name

English

Ethyl (2E,4S)-4-[[(2R,5S)-2-(4-fluorobenzyl)-6-methyl-5-[[(5-methylisoxazol-3-yl)carbonyl]amino]-4-oxoheptanoyl]amino]-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate

Common Name

English

RUPINTRIVIR [USAN]

Common Name

English

2-PENTENOIC ACID, 4-(((2R,5S)-2-((4-FLUOROPHENYL)METHYL)-6-METHYL-5-(((5-METHYL-3-ISOXAZOLYL)CARBONYL)AMINO)-1,4-DIOXOHEPTYL)AMINO)-5-((3S)-2-OXO-3-PYRROLIDINYL)-, ETHYLESTER, (2E,4S)-

Common Name

English

AG7088

Code

English

rupintrivir [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C783