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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyThiorphan
Identification
- Name
- Thiorphan
- Accession Number
- DB08626 (DB01654)
- Type
- Small Molecule
- Groups
- Experimental
- Description
A potent inhibitor of membrane metalloendopeptidase (enkephalinase). Thiorphan potentiates morphine-induced analgesia and attenuates naloxone-precipitated withdrawal symptoms.
- Structure
Structure for DB08626 (Thiorphan)
- Synonyms
- Not Available
- Categories
- UNII
- B79L7B5X3Z
- CAS number
- 76721-89-6
- Weight
- Average: 253.317
Monoisotopic: 253.077264041 - Chemical Formula
- C12H15NO3S
- InChI Key
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N
- InChI
- InChI=1S/C12H15NO3S/c14-11(15)7-13-12(16)10(8-17)6-9-4-2-1-3-5-9/h1-5,10,17H,6-8H2,(H,13,16)(H,14,15)/t10-/m1/s1
- IUPAC Name
- 2-[(2S)-2-benzyl-3-sulfanylpropanamido]acetic acid
- SMILES
- [H][C@](CS)(CC1=CC=CC=C1)C(=O)NCC(O)=O
Pharmacology
- Indication
- Not Available
- Pharmacodynamics
- Not Available
- Mechanism of action
Target Actions Organism UNeprilysin inhibitorHuman - 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
Drug Interaction Drug group Abacavir The serum concentration of Abacavir can be decreased when it is combined with Thiorphan. Approved, Investigational Alfuzosin The serum concentration of Alfuzosin can be increased when it is combined with Thiorphan. Approved, Investigational Alprazolam The serum concentration of Alprazolam can be increased when it is combined with Thiorphan. Approved, Illicit, Investigational Ambroxol acefyllinate The serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Thiorphan. Experimental, Investigational Amineptine The serum concentration of Amineptine can be increased when it is combined with Thiorphan. Illicit, Withdrawn Aminophylline The serum concentration of Aminophylline can be decreased when it is combined with Thiorphan. Approved Amitriptyline The serum concentration of Amitriptyline can be increased when it is combined with Thiorphan. Approved Amitriptylinoxide The serum concentration of Amitriptylinoxide can be increased when it is combined with Thiorphan. Approved, Investigational Amoxapine The serum concentration of Amoxapine can be increased when it is combined with Thiorphan. Approved Boceprevir The serum concentration of Thiorphan can be decreased when it is combined with Boceprevir. Approved, Withdrawn Bromocriptine The serum concentration of Bromocriptine can be increased when it is combined with Thiorphan. Approved, Investigational Butriptyline The serum concentration of Butriptyline can be increased when it is combined with Thiorphan. Approved Cabergoline The serum concentration of Cabergoline can be increased when it is combined with Thiorphan. Approved Carbamazepine The metabolism of Thiorphan can be increased when combined with Carbamazepine. Approved, Investigational Clarithromycin The therapeutic efficacy of Clarithromycin can be decreased when used in combination with Thiorphan. Approved Clomipramine The serum concentration of Clomipramine can be increased when it is combined with Thiorphan. Approved, Investigational, Vet Approved Cyclophosphamide The risk or severity of adverse effects can be increased when Thiorphan is combined with Cyclophosphamide. Approved, Investigational Cyclosporine The serum concentration of Cyclosporine can be increased when it is combined with Thiorphan. Approved, Investigational, Vet Approved Delavirdine The serum concentration of Delavirdine can be decreased when it is combined with Thiorphan. Approved Desipramine The serum concentration of Desipramine can be increased when it is combined with Thiorphan. Approved, Investigational Dibenzepin The serum concentration of Dibenzepin can be increased when it is combined with Thiorphan. Experimental Diethylstilbestrol The serum concentration of Diethylstilbestrol can be decreased when it is combined with Thiorphan. Approved, Investigational Digoxin The serum concentration of Digoxin can be increased when it is combined with Thiorphan. Approved Dihydroergotamine The serum concentration of Dihydroergotamine can be increased when it is combined with Thiorphan. Approved, Investigational Diltiazem The metabolism of Diltiazem can be decreased when combined with Thiorphan. Approved, Investigational Dimetacrine The serum concentration of Dimetacrine can be increased when it is combined with Thiorphan. Approved, Withdrawn Dosulepin The serum concentration of Dosulepin can be increased when it is combined with Thiorphan. Approved Doxepin The serum concentration of Doxepin can be increased when it is combined with Thiorphan. Approved, Investigational Dyphylline The serum concentration of Dyphylline can be decreased when it is combined with Thiorphan. Approved Enfuvirtide The serum concentration of Enfuvirtide can be increased when it is combined with Thiorphan. Approved, Investigational Ergoloid mesylate The serum concentration of Ergoloid mesylate can be increased when it is combined with Thiorphan. Approved Ergonovine The serum concentration of Ergonovine can be increased when it is combined with Thiorphan. Approved Ergotamine The serum concentration of Ergotamine can be increased when it is combined with Thiorphan. Approved Estradiol The serum concentration of Estradiol can be decreased when it is combined with Thiorphan. Approved, Investigational, Vet Approved Estradiol cypionate The serum concentration of Estradiol cypionate can be decreased when it is combined with Thiorphan. Approved, Investigational, Vet Approved Estradiol valerate The serum concentration of Estradiol valerate can be decreased when it is combined with Thiorphan. Approved, Investigational, Vet Approved Ethinyl Estradiol The serum concentration of Ethinyl Estradiol can be decreased when it is combined with Thiorphan. Approved Etravirine The serum concentration of Etravirine can be decreased when it is combined with Thiorphan. Approved Garlic The serum concentration of Thiorphan can be decreased when it is combined with Garlic. Approved, Nutraceutical Imipramine The serum concentration of Imipramine can be increased when it is combined with Thiorphan. Approved Iprindole The serum concentration of Iprindole can be increased when it is combined with Thiorphan. Experimental Lofepramine The serum concentration of Lofepramine can be increased when it is combined with Thiorphan. Experimental Lovastatin The serum concentration of Lovastatin can be increased when it is combined with Thiorphan. Approved, Investigational Melitracen The serum concentration of Melitracen can be increased when it is combined with Thiorphan. Experimental, Investigational Mestranol The serum concentration of Mestranol can be decreased when it is combined with Thiorphan. Approved Methylergometrine The serum concentration of Methylergometrine can be increased when it is combined with Thiorphan. Approved Midazolam The serum concentration of Midazolam can be increased when it is combined with Thiorphan. Approved, Illicit Nefazodone The serum concentration of Nefazodone can be increased when it is combined with Thiorphan. Approved, Withdrawn Nortriptyline The serum concentration of Nortriptyline can be increased when it is combined with Thiorphan. Approved Opipramol The serum concentration of Opipramol can be increased when it is combined with Thiorphan. Investigational Pethidine The risk or severity of adverse effects can be increased when Thiorphan is combined with Pethidine. Approved Protriptyline The serum concentration of Protriptyline can be increased when it is combined with Thiorphan. Approved Riociguat The serum concentration of Riociguat can be increased when it is combined with Thiorphan. Approved Sildenafil The serum concentration of Sildenafil can be increased when it is combined with Thiorphan. Approved, Investigational Simvastatin The serum concentration of Simvastatin can be increased when it is combined with Thiorphan. Approved St. John's Wort The metabolism of Thiorphan can be increased when combined with St. John's Wort. Approved, Investigational, Nutraceutical Tacrolimus The metabolism of Tacrolimus can be decreased when combined with Thiorphan. Approved, Investigational Temsirolimus The risk or severity of adverse effects can be increased when Thiorphan is combined with Temsirolimus. Approved Theophylline The serum concentration of Theophylline can be decreased when it is combined with Thiorphan. Approved Tianeptine The serum concentration of Tianeptine can be increased when it is combined with Thiorphan. Approved, Investigational Tipranavir The serum concentration of Thiorphan can be decreased when it is combined with Tipranavir. Approved, Investigational Triazolam The serum concentration of Triazolam can be increased when it is combined with Thiorphan. Approved, Investigational Trimipramine The serum concentration of Trimipramine can be increased when it is combined with Thiorphan. Approved Valproic Acid The serum concentration of Valproic Acid can be decreased when it is combined with Thiorphan. Approved, Investigational Verapamil The metabolism of Verapamil can be decreased when combined with Thiorphan. Approved Zidovudine The serum concentration of Zidovudine can be decreased when it is combined with Thiorphan. Approved - Food Interactions
- Not Available
References
- Synthesis Reference
Mohammad R. Masjedizadeh, Shao-Yong Wu, "PROCESS FOR SYNTHESIS OF TRITIATED AND DEUTERATED THIORPHAN AND ACETORPHAN." U.S. Patent US20110319656, issued December 29, 2011.
US20110319656- General References
- Not Available
- External Links
- PDB Entries
- 1zdp / 5v48
Clinical Trials
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
Property Value Source Water Solubility 0.445 mg/mL ALOGPS logP 1.78 ALOGPS logP 1.46 ChemAxon logS -2.8 ALOGPS pKa (Strongest Acidic) 4.02 ChemAxon pKa (Strongest Basic) -1.8 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 66.4 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 67.15 m3·mol-1 ChemAxon Polarizability 25.93 Å3 ChemAxon Number of Rings 1 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.937 Blood Brain Barrier + 0.806 Caco-2 permeable - 0.6428 P-glycoprotein substrate Non-substrate 0.7192 P-glycoprotein inhibitor I Non-inhibitor 0.9402 P-glycoprotein inhibitor II Non-inhibitor 0.9827 Renal organic cation transporter Non-inhibitor 0.9466 CYP450 2C9 substrate Non-substrate 0.838 CYP450 2D6 substrate Non-substrate 0.8369 CYP450 3A4 substrate Non-substrate 0.8005 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.923 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.9223 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9729 Ames test Non AMES toxic 0.5567 Carcinogenicity Non-carcinogens 0.9183 Biodegradation Not ready biodegradable 0.5448 Rat acute toxicity 1.6959 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9862 hERG inhibition (predictor II) Non-inhibitor 0.927
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids. These are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- N-acyl-alpha amino acids
- Alternative Parents
- Fatty amides / Benzene and substituted derivatives / Secondary carboxylic acid amides / Monocarboxylic acids and derivatives / Carboxylic acids / Alkylthiols / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- N-acyl-alpha-amino acid / Monocyclic benzene moiety / Fatty amide / Fatty acyl / Benzenoid / Carboxamide group / Secondary carboxylic acid amide / Alkylthiol / Carboxylic acid / Monocarboxylic acid or derivatives show 10 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
Targets
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptide...
- Gene Name
- MME
- Uniprot ID
- P08473
- Uniprot Name
- Neprilysin
- Molecular Weight
- 85513.225 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Drug created on September 15, 2010 15:33 / Updated on June 02, 2018 08:09