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Details

Stereochemistry ACHIRAL
Molecular Formula C31H35F6N4O5P
Molecular Weight 688.5976
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSNETUPITANT

SMILES

CN(C(=O)C(C)(C)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C2=C(C=C(N=C2)N3CC[N+](C)(COP(O)([O-])=O)CC3)C4=C(C)C=CC=C4

InChI

InChIKey=HZIYEEMJNBKMJH-UHFFFAOYSA-N
InChI=1S/C31H35F6N4O5P/c1-20-8-6-7-9-24(20)25-17-27(40-10-12-41(5,13-11-40)19-46-47(43,44)45)38-18-26(25)39(4)28(42)29(2,3)21-14-22(30(32,33)34)16-23(15-21)31(35,36)37/h6-9,14-18H,10-13,19H2,1-5H3,(H-,43,44,45)

HIDE SMILES / InChI

Molecular Formula C31H35F6N4O5P
Molecular Weight 688.5976
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity ( + / - )

Description

Fosnetupitant is a prodrug form of netupitant. Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK-1) receptors. Upon intravenous administration, fosnetupitant is converted by phosphatases to its active form. It competitively binds to and blocks the activity of NK-1 receptors in the central nervous system, by inhibiting binding of substance P (SP) to NK-1 receptors. This prevents delayed emesis, which is associated with SP secretion. AKYNZEO® is a combination of palonosetron, a serotonin-3 receptor antagonist, and netupitant (capsules for oral use) or fosnetupitant (injections for intravenous use). AKYNZEO® for injection is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

CNS Activity

Approval Year

TargetsConditions

Conditions

PubMed

PubMed

TitleDatePubMed
Novel neurokinin-1 antagonists as antiemetics for the treatment of chemotherapy-induced emesis.
2006 Apr 1
Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists.
2006 Mar 1
Efficient synthesis of novel NK1 receptor antagonists: selective 1,4-addition of grignard reagents to 6-chloronicotinic acid derivatives.
2006 Mar 3
A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy.
2014 Jul
Differential and additive suppressive effects of 5-HT3 (palonosetron)- and NK1 (netupitant)-receptor antagonists on cisplatin-induced vomiting and ERK1/2, PKA and PKC activation.
2015 Apr
Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy.
2018 Jul 1
Patents

Sample Use Guides

In Vivo Use Guide
One AKYNZEO (netupitant and palonosetron) capsule administered approximately 1 hour prior to the start of chemotherapy with dexamethasone 12 mg administered orally 30 minutes prior to chemotherapy on day 1 and 8 mg orally once daily on days 2 to 4 (for highly emetogenic chemotherapy, including cisplatin based chemotherapy) or on day 1 with not necessary administration of dexamethasone on days 2 to 4 (for anthracyclines and cyclophosphamide based chemotherapy and chemotherapy not considered highly emetogenic)
Route of Administration: Oral
In Vitro Use Guide
HEK-293 cells were incubated with 5 nM [3H]-netupitant for 40 min at room temperature.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:03:45 UTC 2019
Edited
by admin
on Mon Oct 21 23:03:45 UTC 2019
Record UNII
T672P80L2S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSNETUPITANT
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
FOSNETUPITANT [INN]
Common Name English
FOSNETUPITANT [WHO-DD]
Common Name English
07-PNET
Code English
FOSNETUPITANT [USAN]
Common Name English
PIPERAZINIUM, 4-(5-((2-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-2-METHYL-1-OXOPROPYL)METHYLAMINO)-4-(2-METHYLPHENYL)-2-PYRIDINYL)-1-METHYL-1-((PHOSPHONOOXY)METHYL)-
Systematic Name English
PIPERAZINIUM, 4-(5-((2-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-2-METHYL-1-OXOPROPYL)METHYLAMINO)-4-(2-METHYLPHENYL)-2-PYRIDINYL)-1-METHYL-1-((PHOSPHONOOXY)METHYL)-, INNER SALT
Systematic Name English
Code System Code Type Description
CAS
1703748-89-3
Created by admin on Mon Oct 21 23:03:45 UTC 2019 , Edited by admin on Mon Oct 21 23:03:45 UTC 2019
PRIMARY
INN
10146
Created by admin on Mon Oct 21 23:03:45 UTC 2019 , Edited by admin on Mon Oct 21 23:03:45 UTC 2019
PRIMARY
PUBCHEM
71544786
Created by admin on Mon Oct 21 23:03:45 UTC 2019 , Edited by admin on Mon Oct 21 23:03:45 UTC 2019
PRIMARY
CAS
1431216-59-9
Created by admin on Mon Oct 21 23:03:45 UTC 2019 , Edited by admin on Mon Oct 21 23:03:45 UTC 2019
ALTERNATIVE
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC INJECTION ADMINISTRATION

Tmax PHARMACOKINETIC INJECTION ADMINISTRATION