Telcagepant

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Telcagepant
Accession Number
DB12228  (DB05760)
Type
Small Molecule
Groups
Investigational
Description

Telcagepant has been investigated for the treatment of Migraine. It is an antagonist of the receptor for calcitonin gene-related peptide (CGRP), a primary neuropeptide involved in the pathophysiology of migraine. CGRP and its receptors are found in areas of the central and peripheral nervous system that are important for the transmission of migraine pain. During migraine attacks, CGRP activates these receptors and facilitates the transmission of pain impulses.

Structure
Thumb
Synonyms
Not Available
External IDs
MK-0974 / MK0974
Product Ingredients
IngredientUNIICASInChI Key
Telcagepant potassiumL303VER2NG953077-35-5VESUVMGLUABQCA-LEVQAPRMSA-M
Categories
Not Available
UNII
D42O649ALL
CAS number
781649-09-0
Weight
Average: 566.523
Monoisotopic: 566.206479785
Chemical Formula
C26H27F5N6O3
InChI Key
CGDZXLJGHVKVIE-DNVCBOLYSA-N
InChI
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
IUPAC Name
N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-{2-hydroxy-1H-imidazo[4,5-b]pyridin-1-yl}piperidine-1-carboximidic acid
SMILES
[H][C@]1(CC[C@@]([H])(N=C(O)N2CCC(CC2)N2C(O)=NC3=C2C=CC=N3)C(=O)N(CC(F)(F)F)C1)C1=C(F)C(F)=CC=C1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Telcagepant blocks the binding of CGRP to receptors within the areas of the central and peripheral nervous system that are important for the transmission of migraine pain and thereby is believed to inhibit the transmission of pain signals that lead to migraine headaches.

TargetActionsOrganism
UCalcitonin gene-related peptide 1Not AvailableHuman
UCalcitonin gene-related peptide 2Not AvailableHuman
UCalcitonin gene-related peptide type 1 receptorNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Salvatore CA, Hershey JC, Corcoran HA, Fay JF, Johnston VK, Moore EL, Mosser SD, Burgey CS, Paone DV, Shaw AW, Graham SL, Vacca JP, Williams TM, Koblan KS, Kane SA: 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. J Pharmacol Exp Ther. 2008 Feb;324(2):416-21. Epub 2007 Nov 26. [PubMed:18039958]
  2. Paone DV, Shaw AW, Nguyen DN, Burgey CS, Deng JZ, Kane SA, Koblan KS, Salvatore CA, Mosser SD, Johnston VK, Wong BK, Miller-Stein CM, Hershey JC, Graham SL, Vacca JP, Williams TM: Potent, orally bioavailable calcitonin gene-related peptide receptor antagonists for the treatment of migraine: discovery of 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 (MK-0974). J Med Chem. 2007 Nov 15;50(23):5564-7. Epub 2007 Oct 11. [PubMed:17929795]
  3. Ho TW, Mannix LK, Fan X, Assaid C, Furtek C, Jones CJ, Lines CR, Rapoport AM: Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology. 2008 Apr 15;70(16):1304-12. Epub 2007 Oct 3. [PubMed:17914062]
  4. Link AS, Kuris A, Edvinsson L: Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system. J Headache Pain. 2008 Feb;9(1):5-12. doi: 10.1007/s10194-008-0011-4. Epub 2008 Jan 23. [PubMed:18217201]
External Links
PubChem Compound
11319053
PubChem Substance
347828507
ChemSpider
9494017
BindingDB
50224431
ChEMBL
CHEMBL236593
HET
N7R
Wikipedia
Telcagepant
PDB Entries
3n7r

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAngina Pectoris / Calcitonin Gene-related Peptide Receptor / Coronary Heart Disease (CHD)1
1CompletedTreatmentMigraine Disorders1
1CompletedTreatmentMigraines3
2CompletedTreatmentMigraines2
2TerminatedTreatmentMigraines1
2, 3CompletedTreatmentMigraines1
3CompletedTreatmentCerebrovascular Accidents / Heart Diseases / Migraine Disorders / Peripheral Vascular Disease (PVD) / Transient Ischaemic Attack (TIA) / Vascular Diseases1
3CompletedTreatmentMigraines4

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0191 mg/mLALOGPS
logP3.77ALOGPS
logP4ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)8.08ChemAxon
pKa (Strongest Basic)5.52ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area107.08 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity134.99 m3·mol-1ChemAxon
Polarizability53.2 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Imidazopyridines / Piperidinecarboxamides / Caprolactams / Fluorobenzenes / Azepanes / N-substituted imidazoles / Aryl fluorides / Pyridines and derivatives / Tertiary carboxylic acid amides / Heteroaromatic compounds
show 8 more
Substituents
Alpha-amino acid or derivatives / Imidazopyridine / Piperidinecarboxamide / 1-piperidinecarboxamide / Caprolactam / Azepane / Halobenzene / Fluorobenzene / Aryl fluoride / Aryl halide
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor binding
Specific Function
CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulato...
Gene Name
CALCA
Uniprot ID
P06881
Uniprot Name
Calcitonin gene-related peptide 1
Molecular Weight
13897.755 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Neuropeptide hormone activity
Specific Function
CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulato...
Gene Name
CALCB
Uniprot ID
P10092
Uniprot Name
Calcitonin gene-related peptide 2
Molecular Weight
13705.56 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Specific Function
Adrenomedullin receptor activity
Gene Name
CALCRL
Uniprot ID
Q16602
Uniprot Name
Calcitonin gene-related peptide type 1 receptor
Molecular Weight
52928.98 Da
References
  1. Chan KY, Edvinsson L, Eftekhari S, Kimblad PO, Kane SA, Lynch J, Hargreaves RJ, de Vries R, Garrelds IM, van den Bogaerdt AJ, Danser AH, Maassenvandenbrink A: Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries. J Pharmacol Exp Ther. 2010 Sep 1;334(3):746-52. doi: 10.1124/jpet.110.165993. Epub 2010 Jun 23. [PubMed:20573757]

Drug created on October 20, 2016 15:40 / Updated on November 02, 2018 09:04