TELCAGEPANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H27F5N6O3
Molecular Weight	566.523
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=C(F)C(=CC=C1)[C@@H]2CC[C@@H](NC(=O)N3CCC(CC3)N4C(=O)NC5=C4C=CC=N5)C(=O)N(CC(F)(F)F)C2

InChI

InChIKey=CGDZXLJGHVKVIE-DNVCBOLYSA-N

InChI=1S/C26H27F5N6O3/c27-18-4-1-3-17(21(18)28)15-6-7-19(23(38)36(13-15)14-26(29,30)31)33-24(39)35-11-8-16(9-12-35)37-20-5-2-10-32-22(20)34-25(37)40/h1-5,10,15-16,19H,6-9,11-14H2,(H,33,39)(H,32,34,40)/t15-,19-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C26H27F5N6O3
Molecular Weight	566.523
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22816019
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800024645 http://www.medscape.com/viewarticle/735764_2

Telcagepant (MK-0974) is a calcitonin gene-related peptide receptor antagonist. Merck & Co was developing telcagepant for the treatment of pain. Telcagepant is an extremely potent CGRP antagonist with a Ki = 0.77 (0.07 nM). Telcagepant showed efficacy against acute migraines; however, different patient populations may show more beneficial effects with telcagepant versus triptans. In the acute treatment of migraine, Telcagepant was found to have equal potency to rizatriptan and zolmitriptan in two Phase III clinical trials. Merck & Co has now terminated development of the drug.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Calcitonin gene-related peptide type 1 receptor 7 Target ID: CHEMBL3798 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22816019	Antagonist 2778		2.2 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 103 Sources: https://clinicaltrials.gov/ct2/show/NCT00483704	Palliative		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
14.45 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.07 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.56 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.56 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.64 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.82 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
103.86 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
20.08 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.16 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.16 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
32.47 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
46.65 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20173082	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TELCAGEPANT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00G45S	https://www.1pchem.com/search?query=1P00G45S
AK Scientific	4093AH	https://aksci.com/item_detail.php?cat=4093AH
BLD Pharm	BD287701	http://www.bldpharm.com/search/Search.html?keyword=BD287701
Capot Chemical	23573	https://www.capotchem.com/search.do?q=23573
ChemShuttle	101177	https://www.chemshuttle.com/catalogsearch/result/?q=101177
Hairui	HR140864	http://www.hairuichem.com/en/product/search.do?q=HR140864
Matrix Scientific	143813	http://www.matrixscientific.com/143813.html
MedChem Express	HY-32709	https://www.medchemexpress.com/search.html?q=HY-32709&ft=&fa=&fp=
MolPort	MolPort-028-720-371	https://www.molport.com/shop/molecule-link/MolPort-028-720-371
Molnova	M15947	https://www.molnova.com/en/serch-list.html?keywords=M15947
ShangHai Biochempartner	BCP07257	http://www.biochempartner.com/search_BCP07257
eMolecules	275078827	https://orderbb.emolecules.com/search/#?query=275078827
eMolecules	300796429	https://orderbb.emolecules.com/search/#?query=300796429
eMolecules	44786291	https://orderbb.emolecules.com/search/#?query=44786291
mcule	MCULE-5387188033	https://mcule.com/MCULE-5387188033/
mcule	MCULE-5709493912	https://mcule.com/MCULE-5709493912/

PubMed

Title	Date	PubMed
Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine.	2008 Feb	18039958
A flexible and high throughput liquid chromatography-tandem mass spectrometric assay for the quantitation of telcagepant in human plasma.	2009 May 15	19346171

Patents

Sample Use Guides

In Vivo Use Guide

One telcagepant 140 mg or one 280 mg tablet, orally, twice daily for 12 weeks

Route of Administration: Oral

In Vitro Use Guide

Telcagepant (MK-0974) was very potent in E10 cell-based assay measuring inhibition of CGRP-stimulated cAMP production (IC50 = 2.2 nM), which was only shifted 5-fold (IC50 = 11 nM) in the presence of 50% human serum, suggesting a modest level of protein binding

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:31:28 UTC 2023` Edited by `admin` on `Fri Dec 15 16:31:28 UTC 2023`
Record UNII	D42O649ALL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TELCAGEPANT

Official Name

English

telcagepant [INN]

Common Name

English

N-((3R,6S)-6-(2,3-DIFLUOROPHENYL)-2-OXO-1-(2,2,2-TRIFLUOROETHYL)HEXAHYDRO-1H-AZEPIN-3- YL)-4-(2-OXO-2,3-DIHYDRO-1H-IMIDAZO(4,5-B)PYRIDIN-1-YL)PIPERIDINE-1-CARBOXAMIDE

Systematic Name

English

1-PIPERIDINECARBOXAMIDE, N-((3R,6S)-6-(2,3-DIFLUOROPHENYL)HEXAHYDRO-2-OXO-1-(2,2,2- TRIFLUOROETHYL)-1H-AZEPIN-3-YL)-4-(2,3-DIHYDRO-2-OXO-1H-IMIDAZO(4,5-B)PYRIDIN-1-YL)-

Systematic Name

English

TELCAGEPANT [MI]

Common Name

English

Telcagepant [WHO-DD]

Common Name

English

TELCAGEPANT [MART.]

Common Name

English

MK-0974

Code

English

MK0974

Code

English

TELCAGEPANT [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C241