TELCAGEPANT

Investigational

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

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	MOL RATIO 1 MOL RATIO (average)

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

Description

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 9	Antagonist 2,840		2.2 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 107	Palliative		Phase III 664	Unknown

C_max

Value	Dose	Analyte	Population
8.82 μM	400 mg single, oral	TELCAGEPANT plasma	Homo sapiens
7.56 μM	300 mg single, oral	TELCAGEPANT plasma	Homo sapiens
4.07 μM	200 mg single, oral	TELCAGEPANT plasma	Homo sapiens
5.64 μM	200 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens
7.56 μM	300 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens
14.45 μM	400 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
46.65 μM × h	400 mg single, oral	TELCAGEPANT plasma	Homo sapiens
35.16 μM × h	300 mg single, oral	TELCAGEPANT plasma	Homo sapiens
20.08 μM × h	200 mg single, oral	TELCAGEPANT plasma	Homo sapiens
32.47 μM × h	200 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens
35.16 μM × h	300 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens
103.86 μM × h	400 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
4.7 h	400 mg single, oral	TELCAGEPANT plasma	Homo sapiens
6.2 h	300 mg single, oral	TELCAGEPANT plasma	Homo sapiens
5.3 h	200 mg single, oral	TELCAGEPANT plasma	Homo sapiens
6.4 h	200 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens
6.2 h	300 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens
6 h	400 mg 2 times / day steady-state, oral	TELCAGEPANT plasma	Homo sapiens

Sourcing

Sourcing

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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

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PubMed

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Title	Date	PubMed
A flexible and high throughput liquid chromatography-tandem mass spectrometric assay for the quantitation of telcagepant in human plasma.	2009 May 15	19346171

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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
Record UNII	D42O649ALL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TELCAGEPANT

Official Name

English

MK-0974

Preferred 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

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