OPC-28326

Identification

Name
OPC-28326
Accession Number
DB05461
Type
Small Molecule
Groups
Investigational
Description

At low doses, OPC 28326 selectively vasodilates the femoral arterial bed due to its inhibitory action at alpha-2-adrenoceptors while having minimal action on systemic blood pressure, heart rate and coronary, carotid, vertebral, renal, and mesenteric blood flows. It is the only clinical compound with this profile. It is currently being investigated in the treatment of peripheral vascular diseases and Raynaud's syndrome.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
FR0M0E7AZM
CAS number
Not Available
Weight
Average: 476.051
Monoisotopic: 475.260169804
Chemical Formula
C26H38ClN3O3
InChI Key
QRNMKZJPTYRAIL-UHFFFAOYSA-N
InChI
InChI=1S/C26H35N3O2.ClH.H2O/c1-5-24(30)27-25-19(2)17-22(18-20(25)3)26(31)29-15-12-23(13-16-29)28(4)14-11-21-9-7-6-8-10-21;;/h6-10,17-18,23H,5,11-16H2,1-4H3,(H,27,30);1H;1H2
IUPAC Name
N-(2,6-dimethyl-4-{4-[methyl(2-phenylethyl)amino]piperidine-1-carbonyl}phenyl)propanamide hydrate hydrochloride
SMILES
O.Cl.CCC(=O)NC1=C(C)C=C(C=C1C)C(=O)N1CCC(CC1)N(C)CCC1=CC=CC=C1

Pharmacology

Indication

Investigated for use/treatment in peripheral vascular disease and raynaud's disease.

Pharmacodynamics

At low doses, OPC 28326 selectively vasodilates the femoral arterial bed due to its inhibitory action at alpha-2-adrenoceptors while having minimal action on systemic blood pressure, heart rate and coronary, carotid, vertebral, renal, and mesenteric blood flows.

Mechanism of action

At low doses, OPC 28326 selectively vasodilates the femoral arterial bed due to its inhibitory action at alpha-2C-adrenoceptors. Other studies have also reported selectivity for a-2B-adrenoceptors.

TargetActionsOrganism
U5-hydroxytryptamine receptor 2BNot AvailableHumans
UAlpha-2C adrenergic receptorNot AvailableHumans
UAlpha-2B adrenergic receptorNot AvailableHumans
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

10 mg and 40 mg was well tolerated during clinical trials with Raynaud's patients

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Sumi M, Sata M, Hashimoto A, Imaizumi T, Yanaga K, Ohki T, Mori T, Nagai R: OPC-28326, a selective femoral arterial vasodilator, augments ischemia induced angiogenesis. Biomed Pharmacother. 2007 May;61(4):209-15. Epub 2006 Dec 28. [PubMed:17223008]
  2. Wise RA, Wigley FM, White B, Leatherman G, Zhong J, Krasa H, Kambayashi J, Orlandi C, Czerwiec FS: Efficacy and tolerability of a selective alpha(2C)-adrenergic receptor blocker in recovery from cold-induced vasospasm in scleroderma patients: a single-center, double-blind, placebo-controlled, randomized crossover study. Arthritis Rheum. 2004 Dec;50(12):3994-4001. [PubMed:15593189]
  3. Orito K, Imaizumi T, Yoshida K, Kishi M, Fujiki H, Mori T: Effect of oral OPC-28326, a selective femoral arterial vasodilator, on hindlimb subcutaneous tissue temperature in conscious dogs under buprenorphine sedation. Jpn J Pharmacol. 2002 Jan;88(1):119-22. [PubMed:11855671]
  4. Orito K, Kishi M, Imaizumi T, Nakazawa T, Hashimoto A, Mori T, Kambe T: alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator. Br J Pharmacol. 2001 Oct;134(4):763-70. [PubMed:11606316]
  5. Orito K, Imaizumi T, Yoshida K, Fujiki H, Kishi M, Teramoto S, Tanaka M, Shimizu H, Tominaga M, Kimura Y, Kambayashi J, Mori T: Mechanisms of action of OPC-28326, a selective hindlimb vasodilator. J Pharmacol Exp Ther. 1999 Nov;291(2):604-11. [PubMed:10525078]
  6. Sun B, Lockyer S, Li J, Chen R, Yoshitake M, Kambayashi JI: OPC-28326, a selective femoral vasodilator, is an alpha2C-adrenoceptor-selective antagonist. J Pharmacol Exp Ther. 2001 Nov;299(2):652-8. [PubMed:11602678]
External Links
PubChem Compound
15942713
PubChem Substance
175427011
ChemSpider
11252547

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP4.28ChemAxon
pKa (Strongest Acidic)13.85ChemAxon
pKa (Strongest Basic)9.71ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.65 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity129.32 m3·mol-1ChemAxon
Polarizability49.91 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9443
Blood Brain Barrier+0.7873
Caco-2 permeable+0.5571
P-glycoprotein substrateSubstrate0.8063
P-glycoprotein inhibitor IInhibitor0.5728
P-glycoprotein inhibitor IIInhibitor0.6503
Renal organic cation transporterNon-inhibitor0.7533
CYP450 2C9 substrateNon-substrate0.78
CYP450 2D6 substrateNon-substrate0.7391
CYP450 3A4 substrateSubstrate0.6819
CYP450 1A2 substrateNon-inhibitor0.8663
CYP450 2C9 inhibitorNon-inhibitor0.8942
CYP450 2D6 inhibitorNon-inhibitor0.7815
CYP450 2C19 inhibitorNon-inhibitor0.8995
CYP450 3A4 inhibitorNon-inhibitor0.6302
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9468
Ames testNon AMES toxic0.7529
CarcinogenicityNon-carcinogens0.7755
BiodegradationNot ready biodegradable0.9713
Rat acute toxicity2.5675 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9302
hERG inhibition (predictor II)Inhibitor0.7769
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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 1-benzoylpiperidines. These are compounds containing a piperidine ring substituted at the 1-position with a benzoyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoyl derivatives
Direct Parent
1-benzoylpiperidines
Alternative Parents
N-benzoylpiperidines / Acylaminobenzoic acid and derivatives / Phenethylamines / Anilides / Benzamides / m-Xylenes / N-arylamides / Aminopiperidines / Aralkylamines / Tertiary carboxylic acid amides
show 9 more
Substituents
N-benzoylpiperidine / 1-benzoylpiperidine / Acylaminobenzoic acid or derivatives / Phenethylamine / Anilide / N-acyl-piperidine / Benzoic acid or derivatives / Benzamide / N-arylamide / Xylene
show 24 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da

Drug created on November 18, 2007 11:25 / Updated on March 01, 2020 19:32

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