RAVUCONAZOLE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H17F2N5OS
Molecular Weight	437.465
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=OPAHEYNNJWPQPX-RCDICMHDSA-N

InChI=1S/C22H17F2N5OS/c1-14(21-28-20(10-31-21)16-4-2-15(9-25)3-5-16)22(30,11-29-13-26-12-27-29)18-7-6-17(23)8-19(18)24/h2-8,10,12-14,30H,11H2,1H3/t14-,22+/m0/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 8504

Conditions

Condition	Modality	Highest Phase	Product
Onychomycosis 18 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27904057	Curative	Phase II 1147	Unknown Approved Use Unknown
Fungal infection 21 Sources: https://clinicaltrials.gov/ct2/show/NCT00064311	Preventing	Phase II 1147	Unknown Approved Use Unknown
Invasive aspergillosis 15 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11083644	Curative	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1052 ng/mL CLINICAL TRIAL https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005283462	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: nelfinavir	nelfinavir	RAVUCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9133 ng/mL CLINICAL TRIAL https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005283462	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: nelfinavir	nelfinavir	RAVUCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
13872 ng × h/mL CLINICAL TRIAL https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005283462	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: nelfinavir	nelfinavir	RAVUCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
153561 ng × h/mL CLINICAL TRIAL https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005283462	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: nelfinavir	nelfinavir	RAVUCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
192 h CLINICAL TRIAL https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1177/0091270005283462	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: nelfinavir	nelfinavir	RAVUCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% CLINICAL TRIAL https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1468-3083.2005.01212.x	200 mg single, topical dose: 200 mg route of administration: Topical experiment type: SINGLE co-administered:		RAVUCONAZOLE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 OCT2 779 CYP2B6 926 CYP2C19 2057 OAT1 725 CYP3A 227 OAT3 747 OATP1B1 1079 P-gp 1741 OATP1B3 961 BCRP 910 MATE1 415 CYP1A2 2153 MATE2-K 77		CYP3A 142 CYP2B 32

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2B 41	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/16432271/	likely
CYP3A 317	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/16432271/	likely
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
MATE2-K 77	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	no
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 1.14 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 1.51 uM]
CYP3A 317	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 2.28 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 2.69 uM]
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 2.8 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 7.12 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29768713/	yes [IC50 7.49 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16432271/	yes [Ki 1.1 uM]	no (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/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
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
Hairui	FOSA04001	http://www.hairuichem.com/en/product/search.do?q=FOSA04001
mcule	MCULE-1506064001	https://mcule.com/MCULE-1506064001/
mcule	MCULE-9138248395	https://mcule.com/MCULE-9138248395/
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

PubMed

Title	Date	PubMed
Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility.	2014-05-08	24564525
Discovery of novel indazole-linked triazoles as antifungal agents.	2007-06-15	17433670
In vitro activity of ravuconazole against 923 clinical isolates of nondermatophyte filamentous fungi.	2005-12	16304186
Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi.	2003-08	12904365
Synthesis of novel water soluble benzylazolium prodrugs of lipophilic azole antifungals.	2002-10-07	12217374
In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp.	2002-06	12019081
Efficacy of ravuconazole in treatment of systemic murine histoplasmosis.	2002-03	11850289
Antifungals: what's in the pipeline.	2001-10	11587930
Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis.	2000-12	11083644
In vitro activity of the new triazole BMS-207147 against Aspergillus species in comparison with itraconazole and amphotericin B.	2000-02	10639380
New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)-quinazolinones.	1998-05-21	9599237
New azole antifungals. 2. Synthesis and antifungal activity of heterocyclecarboxamide derivatives of 3-amino-2-aryl-1-azolyl-2-butanol.	1998-05-21	9599236
Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis.	1996-10	8891122
In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.	1996-10	8891121

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

ravuconazole [INN]

Preferred Name

English

RAVUCONAZOLE

Official Name

English

Benzonitrile, 4-[2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-thiazolyl]-

Systematic Name

English

BMS-207147

Code

English

Benzonitrile, 4-[2-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-thiazolyl]-, [R-(R*,R*)]-

Systematic Name

English

RAVUCONAZOLE [MI]

Common Name

English

RAVUCONAZOLE [MART.]

Common Name

English

Ravuconazole [WHO-DD]

Common Name

English

4-[2-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-thiazolyl]benzonitrile

Systematic Name

English

ER-30346

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C514