You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameOlcegepant
Accession NumberDB04869
TypeSmall Molecule
GroupsInvestigational
DescriptionBoehringer Ingelheim Pharmaceuticals’ olcegepant (BIBN 4096) is a selective Calcitonin Gene-Related Peptide (CGRP) antagonist, a new class of drugs in development for the treatment of acute migraine attacks. Olcegepant is undergoing phase II trials in Europe and the US, with preliminary results suggesting that CGRP antagonists may represent a potential new approach to the treatment of migraine.
Structure
Thumb
SynonymsNot Available
External Identifiers
  • BIBN 4096
  • BIBN 4096 BS
  • BIBN-4096BS
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIWOA5J8TX6M
CAS number204697-65-4
WeightAverage: 869.645
Monoisotopic: 867.206690953
Chemical FormulaC38H47Br2N9O5
InChI KeyITIXDWVDFFXNEG-JHOUSYSJSA-N
InChI
InChI=1S/C38H47Br2N9O5/c39-29-21-25(22-30(40)34(29)50)23-33(45-37(53)48-15-10-28(11-16-48)49-24-26-5-1-2-6-31(26)44-38(49)54)35(51)43-32(7-3-4-12-41)36(52)47-19-17-46(18-20-47)27-8-13-42-14-9-27/h1-2,5-6,8-9,13-14,21-22,28,32-33,50H,3-4,7,10-12,15-20,23-24,41H2,(H,43,51)(H,44,54)(H,45,53)/t32-,33+/m0/s1
IUPAC Name
(2R)-N-[(2S)-6-amino-1-oxo-1-[4-(pyridin-4-yl)piperazin-1-yl]hexan-2-yl]-3-(3,5-dibromo-4-hydroxyphenyl)-2-({hydroxy[4-(2-hydroxy-3,4-dihydroquinazolin-3-yl)piperidin-1-yl]methylidene}amino)propanimidic acid
SMILES
[H][C@@](CCCCN)(N=C(O)[C@@]([H])(CC1=CC(Br)=C(O)C(Br)=C1)N=C(O)N1CCC(CC1)N1CC2=CC=CC=C2N=C1O)C(=O)N1CCN(CC1)C1=CC=NC=C1
Pharmacology
IndicationFor the treatment of migraine headaches.
Structured Indications Not Available
PharmacodynamicsOlcegepant is a calcitonin gene-related peptide (CGRP) antagonist. In preclinical studies, olcegepant attenuated arterial dilation induced by CGRP or electrical stimulation. In a phase II clinical trial, olcegepant reduced the severity of headache in 60% of migraine sufferers and met secondary endpoints including headache-free rate and rate of sustained response. Only mild-to-moderate transient adverse events were observed, with no adverse cardiovascular symptoms reported. The compound appears to be an effective anti-migraine medication that is well tolerated and does not display the vasoconstrictive effect that precludes the use of triptans and dihydroergotamine in certain patients.
Mechanism of actionMigraine involves dysfunction of brainstem pathways that normally modulate sensory input. The involvement of calcitonin gene-related peptide (CGRP) in migraine pathology is supported by both clinical and experimental evidence. The release of CGRP and other neuropeptides from trigeminal nerves is thought to mediate neurogeate inflammation within the meninges which contributes to the generation of severe cerebral pain experienced during migraine attack. CGRP antagonists such as olcegepant bind at CGRP receptors, blocking the effect CGRP and thus reducing inflammation.
TargetKindPharmacological actionActionsOrganismUniProt ID
Calcitonin gene-related peptide 1ProteinunknownNot AvailableHumanP06881 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Recober A, Russo AF: Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment. IDrugs. 2007 Aug;10(8):566-74. [PubMed:17665333 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9692
Blood Brain Barrier-0.8022
Caco-2 permeable-0.779
P-glycoprotein substrateSubstrate0.8342
P-glycoprotein inhibitor INon-inhibitor0.696
P-glycoprotein inhibitor IINon-inhibitor0.8823
Renal organic cation transporterNon-inhibitor0.8041
CYP450 2C9 substrateNon-substrate0.8591
CYP450 2D6 substrateNon-substrate0.7829
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8027
CYP450 2C9 inhibitorNon-inhibitor0.6565
CYP450 2D6 inhibitorNon-inhibitor0.808
CYP450 2C19 inhibitorNon-inhibitor0.6908
CYP450 3A4 inhibitorNon-inhibitor0.6928
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7051
Ames testNon AMES toxic0.6406
CarcinogenicityNon-carcinogens0.8528
BiodegradationNot ready biodegradable0.9946
Rat acute toxicity2.2550 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7242
hERG inhibition (predictor II)Inhibitor0.8525
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0316 mg/mLALOGPS
logP3.55ALOGPS
logP1.08ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)4.17ChemAxon
pKa (Strongest Basic)10.24ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area186.94 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity216.88 m3·mol-1ChemAxon
Polarizability84.67 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPeptides
Alternative Parents
Substituents
  • Alpha peptide
  • N-carbamoyl-alpha-amino acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-arylpiperazine
  • Pyridinylpiperazine
  • Alpha-amino acid amide
  • Quinazoline
  • Phenylpropylamine
  • Amphetamine or derivatives
  • N-substituted-alpha-amino acid
  • Piperidinecarboxylic acid
  • Piperidinecarboxamide
  • 1-piperidinecarboxamide
  • Dialkylarylamine
  • 2-bromophenol
  • 2-halophenol
  • Pyrimidone
  • Phenol
  • Halobenzene
  • Bromobenzene
  • Aminopyridine
  • 4-aminopiperidine
  • Fatty acyl
  • Benzenoid
  • Pyrimidine
  • Pyridine
  • Piperidine
  • Piperazine
  • Fatty amide
  • 1,4-diazinane
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl bromide
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Urea
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organobromide
  • Organohalogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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 neuromodulator role. It also elevates platelet cAMP.
Gene Name:
CALCA
Uniprot ID:
P06881
Molecular Weight:
13897.755 Da
References
  1. Recober A, Russo AF: Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment. IDrugs. 2007 Aug;10(8):566-74. [PubMed:17665333 ]
Comments
comments powered by Disqus
Drug created on October 20, 2007 04:10 / Updated on August 17, 2016 12:24