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Identification
NameAsimadoline
Accession NumberDB05104
TypeSmall Molecule
GroupsInvestigational
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
SynonymsNot Available
External Identifiers
  • EMD 61753
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
CategoriesNot Available
UNIID0VK52NV5M
CAS number153205-46-0
WeightAverage: 414.5393
Monoisotopic: 414.230728214
Chemical FormulaC27H30N2O2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Phenylacetamide
  • Phenylpropylamine
  • Aralkylamine
  • N-alkylpyrrolidine
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Carboxamide group
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in irritable bowel syndrome (IBS).
PharmacodynamicsNot Available
Mechanism of actionAsimadoline 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.
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 organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot 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 synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates th...
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24