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Details

Stereochemistry ABSOLUTE
Molecular Formula C16H15FN6OS
Molecular Weight 358.393
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FEZOLINETANT

SMILES

C[C@H]1N(CCN2C1=NN=C2C3=NC(C)=NS3)C(=O)C4=CC=C(F)C=C4

InChI

InChIKey=PPSNFPASKFYPMN-SECBINFHSA-N
InChI=1S/C16H15FN6OS/c1-9-13-19-20-14(15-18-10(2)21-25-15)23(13)8-7-22(9)16(24)11-3-5-12(17)6-4-11/h3-6,9H,7-8H2,1-2H3/t9-/m1/s1

HIDE SMILES / InChI
Molecular Formula C16H15FN6OS
Molecular Weight 358.393
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Fezolinetant (ESN-364) is an antagonist of the neurokinin-3 receptor. It suppresses the hypothalamic-pituitary-gonadal axis. Ogeda is developing fezolinetant for the treatment of hot flashes (vasomotor symptoms) in postmenopausal women.

CNS Activity

Originator

Approval Year

2023
455
Targets

Targets

Primary TargetPharmacologyConditionPotency
Neuromedin-K receptor
1
Target ID: P29371
Gene ID: 6870.0
Gene Symbol: TACR3
Target Organism: Homo sapiens (Human)
Antagonist
2778
 7.6 null [pKi]
PubMed

PubMed

TitleDatePubMed
Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II).
2015 Jul 9
Patents

Patents

US20170095472
1

Sample Use Guides

In Vivo Use Guide
Phase 2 study for the treatment of hot flashes (vasomotor symptoms) in postmenopausal women. The dose of ESN364 varies across 7 treatment groups, with groups receiving once a day or twice a day blinded study drug. Doses range from 30 mg to 180 mg total daily dosing for 12 weeks.
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Sat Dec 16 02:53:17 GMT 2023
Edited
by admin
on Sat Dec 16 02:53:17 GMT 2023
Record UNII
83VNE45KXX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FEZOLINETANT
INN   WHO-DD  
USAN   INN  
Official Name English
AS-3472693-00
Code English
(4-FLUOROPHENYL)((8R)-8-METHYL-3-(3-METHYL-1,2,4- THIADIAZOL-5-YL)-5,6-DIHYDRO-1,2,4-TRIAZOLO(4,3-A)PYRAZIN- 7(8H)-YL)METHANONE
Systematic Name English
FEZOLINETANT [USAN]
Common Name English
METHANONE, ((8R)-5,6-DIHYDRO-8-METHYL-3-(3-METHYL-1,2,4-THIADIAZOL-5-YL)-1,2,4-TRIAZOLO(4,3-A)PYRAZIN-7(8H)-YL)(4-FLUOROPHENYL)-
Systematic Name English
VEOZAH
Brand Name English
fezolinetant [INN]
Common Name English
ES-256364
Code English
A-2693
Code English
(4-FLUOROPHENYL)((8R)-5,6-DIHYDRO-8-METHYL-3-(3-METHYL-1,2,4-THIADIAZOL-5-YL)-(1,2,4)TRIAZOLO(4,3-A)PYRAZIN-7(8H)-YL)METHANONE
Systematic Name English
A2693
Code English
((8R)-5,6-DIHYDRO-8-METHYL-3-(3-METHYL-1,2,4-THIADIAZOL-5-YL)-1,2,4-TRIAZOLO(4,3-A)PYRAZIN-7(8H)-YL)(4-FLUOROPHENYL)METHANONE
Systematic Name English
AS3472693-00
Code English
ESN-364
Code English
Fezolinetant [WHO-DD]
Common Name English
ESN364
Code English
Code System Code Type Description
USAN
HI-226
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
NCI_THESAURUS
C171845
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
DRUG BANK
DB15669
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
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WIKIPEDIA
FEZOLINETANT
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
PUBCHEM
117604931
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
EPA CompTox
DTXSID601103615
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
SMS_ID
100000174631
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
CAS
1629229-37-3
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
FDA UNII
83VNE45KXX
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
INN
10205
Created by admin on Sat Dec 16 02:53:17 GMT 2023 , Edited by admin on Sat Dec 16 02:53:17 GMT 2023
PRIMARY
Related Record Type Details
NEUROMEDIN-K RECEPTOR
TARGET -> INHIBITOR
Related Record Type Details
Structure of FEZOLINETANT
ACTIVE MOIETY
INTERVENTION(S): In part 1 of the study, men received single oral doses of 3-180 mg or placebo. In part 2, men received placebo or 20, 60, or 180 mg each day for 10 days. In part 3, women received placebo or 20, 60, or 180 mg each day for 21 days, where dosing was initiated on day 3 +/- 2 after menses. RESULTS: ESN364 was well-tolerated and rapidly bioavailable with linear pharmacokinetics and no drug accumulation with repeated, daily oral administration. Drug treatment dose-dependently decreased basal LH, but not FSH, and consequently decreased estradiol and progesterone (in women) as well as testosterone (in men). The hormonal changes in women corresponded to delayed ovulation, decreased endometrial thickening, impeded follicular maturation, and prolongation of the menstrual cycle. Drug effects were rapidly reversible. CONCLUSIONS: Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women. These results suggest that ESN364 may offer therapeutic benefit in the treatment of women's health disorders with a mitigated risk of menopausal-like adverse events.
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