Asimadoline

Identification

Name
Asimadoline
Accession Number
DB05104
Type
Small Molecule
Groups
Investigational
Description

Asimadoline is a proprietary small molecule therapeutic, originally discovered by Merck KGaA of Darmstadt, Germany. Asimadoline was originally developed to treat peripheral pain such as arthritis. Asimadoline is an orally administered agent that acts as a kappa opioid receptor agonist. It has shown encouraging clinical efficacy for the treatment of IBS in a barostat study in IBS patients and has the potential for treating other gastrointestinal diseases.

Structure
Thumb
Synonyms
Not Available
External IDs
EMD 61753
Categories
UNII
D0VK52NV5M
CAS number
153205-46-0
Weight
Average: 414.5393
Monoisotopic: 414.230728214
Chemical Formula
C27H30N2O2
InChI Key
JHLHNYVMZCADTC-LOSJGSFVSA-N
InChI
InChI=1S/C27H30N2O2/c1-28(25(21-11-5-2-6-12-21)20-29-18-17-24(30)19-29)27(31)26(22-13-7-3-8-14-22)23-15-9-4-10-16-23/h2-16,24-26,30H,17-20H2,1H3/t24-,25+/m0/s1
IUPAC Name
N-[(1S)-2-[(3S)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-N-methyl-2,2-diphenylacetamide
SMILES
CN([[email protected]](CN1CC[[email protected]](O)C1)C1=CC=CC=C1)C(=O)C(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

Investigated for use/treatment in irritable bowel syndrome (IBS).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Asimadoline is an orally administered agent that acts as a kappa opioid receptor agonist. Kappa opioid receptors are found mostly in the digestive tract and are believed to play an important role in control of visceral pain and bowel motility. As such, kappa opioid agonists are ideal candidates to relieve the pain, discomfort an impaired motility common to IBS and other gastrointestinal disorders.

TargetActionsOrganism
UKappa-type opioid 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. Delvaux M, Beck A, Jacob J, Bouzamondo H, Weber FT, Frexinos J: Effect of asimadoline, a kappa opioid agonist, on pain induced by colonic distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2004 Jul 15;20(2):237-46. [PubMed:15233705]
  2. Delgado-Aros S, Chial HJ, Camilleri M, Szarka LA, Weber FT, Jacob J, Ferber I, McKinzie S, Burton DD, Zinsmeister AR: Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans. Am J Physiol Gastrointest Liver Physiol. 2003 Apr;284(4):G558-66. [PubMed:12631557]
  3. Szarka LA, Camilleri M, Burton D, Fox JC, McKinzie S, Stanislav T, Simonson J, Sullivan N, Zinsmeister AR: Efficacy of on-demand asimadoline, a peripheral kappa-opioid agonist, in females with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2007 Nov;5(11):1268-75. Epub 2007 Sep 27. [PubMed:17900994]
  4. Schreiber R, Bartoszyk GD, Kunzelmann K: The kappa-opioid receptor agonist asimadoline inhibits epithelial transport in mouse trachea and colon. Eur J Pharmacol. 2004 Oct 25;503(1-3):185-90. [PubMed:15496313]
External Links
PubChem Compound
179340
PubChem Substance
175426945
ChemSpider
156107
BindingDB
50366356
ChEMBL
CHEMBL1190199

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
2CompletedTreatmentAtopic Dermatitis (AD) / Pruritus1
2CompletedTreatmentIrritable Bowel Syndrome (IBS)2
2TerminatedTreatmentPost-Operative Ileus (POI)1
3CompletedTreatmentDiarrhoea Predominant Irritable Bowel Syndrome1

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
Water Solubility0.0112 mg/mLALOGPS
logP3.66ALOGPS
logP3.99ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)14.85ChemAxon
pKa (Strongest Basic)8.17ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area43.78 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity124.81 m3·mol-1ChemAxon
Polarizability46.08 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.991
Blood Brain Barrier+0.8327
Caco-2 permeable+0.5588
P-glycoprotein substrateSubstrate0.7863
P-glycoprotein inhibitor IInhibitor0.6416
P-glycoprotein inhibitor IINon-inhibitor0.5923
Renal organic cation transporterInhibitor0.6376
CYP450 2C9 substrateNon-substrate0.669
CYP450 2D6 substrateNon-substrate0.6546
CYP450 3A4 substrateSubstrate0.6221
CYP450 1A2 substrateNon-inhibitor0.9447
CYP450 2C9 inhibitorNon-inhibitor0.8552
CYP450 2D6 inhibitorInhibitor0.5443
CYP450 2C19 inhibitorNon-inhibitor0.5587
CYP450 3A4 inhibitorNon-inhibitor0.8641
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8761
Ames testNon AMES toxic0.8548
CarcinogenicityNon-carcinogens0.9519
BiodegradationNot ready biodegradable0.8859
Rat acute toxicity2.4203 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7947
hERG inhibition (predictor II)Inhibitor0.5233
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 diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Phenylacetamides / Aralkylamines / N-alkylpyrrolidines / Tertiary carboxylic acid amides / Trialkylamines / Secondary alcohols / Amino acids and derivatives / 1,2-aminoalcohols / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Diphenylmethane / Phenylacetamide / Aralkylamine / N-alkylpyrrolidine / Pyrrolidine / Tertiary carboxylic acid amide / 1,2-aminoalcohol / Amino acid or derivatives / Carboxamide group / Secondary alcohol
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 15:35