FOSRAVUCONAZOLE L-LYSINE ETHANOLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H20F2N5O5PS.C6H14N2O2.C2H6O
Molecular Weight	739.727
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of FOSRAVUCONAZOLE L-LYSINE ETHANOLATE

Structure Search

SMILES

CCO.NCCCC[C@H](N)C(O)=O.C[C@@H](C1=NC(=CS1)C2=CC=C(C=C2)C#N)[C@@](CN3C=NC=N3)(OCOP(O)(O)=O)C4=CC=C(F)C=C4F

InChI

InChIKey=VOWYGLHOVNSCSA-NRVKWRQJSA-N

InChI=1S/C23H20F2N5O5PS.C6H14N2O2.C2H6O/c1-15(22-29-21(10-37-22)17-4-2-16(9-26)3-5-17)23(11-30-13-27-12-28-30,34-14-35-36(31,32)33)19-7-6-18(24)8-20(19)25;7-4-2-1-3-5(8)6(9)10;1-2-3/h2-8,10,12-13,15H,11,14H2,1H3,(H2,31,32,33);5H,1-4,7-8H2,(H,9,10);3H,2H2,1H3/t15-,23+;5-;/m00./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27904057 | https://clinicaltrials.gov/ct2/show/NCT00064311

Ravuconazole is a triazole with antifungal properties that inhibits cytochrome P450 sterol 14a-demethylase, an enzyme involved in sterol synthesis, resulting in lysis of the fungal cell wall and fungal cell death. It was investigated for the treatment of aspergillosis, candidiasis, and onychomycosis, but these studies were discontinued. Ravuconazole is now in phase II clinical trials to investigate efficacy in preventing fungal infections in patients undergoing chemotherapy and stem cell transplantation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
cytochrome P450 sterol 14a-demethylase 4 Target ID: cytochrome P450 sterol 14a-demethylase Sources: https://www.ncbi.nlm.nih.gov/pubmed/15989596	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Onychomycosis 18 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27904057	Curative	Phase II 1132	Unknown Approved Use Unknown
Fungal infection 21 Sources: https://clinicaltrials.gov/ct2/show/NCT00064311	Preventing	Phase II 1132	Unknown Approved Use Unknown
Invasive aspergillosis 14 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11083644	Curative	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 OCT2 647 CYP2B6 810 CYP2C19 1478 OAT1 599 CYP3A 214 OAT3 642 OATP1B1 788 P-gp 1461 OATP1B3 706 BCRP 699 MATE1 306 CYP1A2 1524 MATE2-K 9		CYP3A 129 CYP2B 32

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2B 40	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/16432271/	likely
CYP3A 298	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/16432271/	likely
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16432271/	moderate [Ki 1.1 uM]	weak (co-administration study) Comment: Increased Nelfinavir Cmax and AUC by 30.7%, 31.9% (day 2) and decreased by 7.9%, increased by 16.2% (day 29) Sources: https://pubmed.ncbi.nlm.nih.gov/16432271/
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
MATE2-K 9	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 1.14 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 1.51 uM]
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 2.28 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 2.69 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 2.8 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 7.12 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 7.49 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/24564525/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0024L2	https://www.1pchem.com/search?query=1P0024L2
AK Scientific	X5181	https://aksci.com/item_detail.php?cat=X5181
Alfa Chemistry	ACM170864296	http://www.alfa-chemistry.com/search.aspx?q=ACM170864296
Angene	AGN-PC-0QCAH4	http://www.angenechemical.com/productshow/AGN-PC-0QCAH4.html
AstaTech	43027	http://astatechinc.com/CPSResult.php?CRNO=43027
BOC Sciences	170864-29-6	http://www.bocsci.com/description.asp?cas=170864-29-6
BOC Sciences	182760-06-1	http://www.bocsci.com/description.asp?cas=182760-06-1
Capot Chemical	31958	https://www.capotchem.com/search.do?q=31958
Cayman Chemical	18750	http://www.caymanchem.com/app/template/Product.vm/catalog/18750
Chem Scene	CS-6927	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-6927
Hairui	FOSA04001	http://www.hairuichem.com/en/product/search.do?q=FOSA04001
MedChem Express	HY-14272	https://www.medchemexpress.com/search.html?q=HY-14272&ft=&fa=&fp=
MolPort	MolPort-005-935-605	https://www.molport.com/shop/molecule-link/MolPort-005-935-605
MolPort	MolPort-046-069-036	https://www.molport.com/shop/molecule-link/MolPort-046-069-036
MuseChem	R049436	https://www.musechem.com/product/R049436.html
ShangHai Biochempartner	BCP000635	http://www.biochempartner.com/search_BCP000635
ShangHai Biochempartner	BCP05803	http://www.biochempartner.com/search_BCP05803
TargetMol	T7152	https://www.targetmol.com/search?keyword=T7152
Tetrahedron	TS93450	http://www.thsci.com/search.do?q=TS93450
Toronto Research Chemicals	C986750	https://www.trc-canada.com/product-detail/?CatNum=C986750
Toronto Research Chemicals	R128000	https://www.trc-canada.com/product-detail/?CatNum=R128000
Wonderchem	WD05GK9	http://www.wonder-chem.com/search.html?text=WD05GK9
eMolecules	110046822	https://orderbb.emolecules.com/search/#?query=110046822
eMolecules	29936409	https://orderbb.emolecules.com/search/#?query=29936409
eMolecules	300463698	https://orderbb.emolecules.com/search/#?query=300463698
eMolecules	53926975	https://orderbb.emolecules.com/search/#?query=53926975
eNovation Chemicals	D154973	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D154973&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1506064001	https://mcule.com/MCULE-1506064001/
mcule	MCULE-9138248395	https://mcule.com/MCULE-9138248395/

PubMed

Title	Date	PubMed
In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.	1996 Oct	8891121
New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)-quinazolinones.	1998 May 21	9599237
In vitro activity of the new triazole BMS-207147 against Aspergillus species in comparison with itraconazole and amphotericin B.	2000 Feb	10639380
In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp.	2002 Jun	12019081
Synthesis of novel water soluble benzylazolium prodrugs of lipophilic azole antifungals.	2002 Oct 7	12217374
In vitro activity of ravuconazole against 923 clinical isolates of nondermatophyte filamentous fungi.	2005 Dec	16304186
Discovery of novel indazole-linked triazoles as antifungal agents.	2007 Jun 15	17433670
Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility.	2014 May 8	24564525

Patents

Sample Use Guides

In Vivo Use Guide

In an asceding oral dose study, single doses of ravuconazole (from 50 to 800 mg once daily)

Route of Administration: Oral

In Vitro Use Guide

Ravuconazole showed very potent in vitro anti-T. cruzi activity with minimal inhibitory concentrations (MIC) of 300 and 1 nM against the extracellular epimastigote and intracellular amastigote forms, respectively.

Name

Type

Language

FOSRAVUCONAZOLE L-LYSINE ETHANOLATE

Common Name

English

((1R,2R)-2-(4-(4-CYANOPHENYL)-2-THIAZOLYL)-1-(2,4-DIFLUOROPHENYL)-1-(1H-1,2,4-TRIAZOL-1-YLMETHYL)PROPOXY) METHYL ESTER COMPOUND WITH LYSINE, ETHANOLATE (1:1:1)

Systematic Name

English

FOSRAVUCONAZOLE L-LYSINE ETHANOLATE [MI]

Common Name

English

FOSRAVUCONAZOLE L-LYSINE ETHANOLATE [JAN]

Common Name

English

Fosravuconazole L-lysine ethanolate [WHO-DD]

Common Name

English

L-LYSINE, COMPD. WITH 4-(2-((1R,2R)-2-(2,4-DIFLUOROPHENYL)-1-METHYL-2-((PHOSPHONOOXY)METHOXY)-3-(1H-1,2,4-TRIAZOL-1-YL)PROPYL)-4-THIAZOLYL)BENZONITRILE AND ETHANOL (1:1:1)

Systematic Name

English

Code System Code Type Description

CAS

914361-45-8