Faropenem medoxomil

Identification

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Name
Faropenem medoxomil
Accession Number
DB05659
Type
Small Molecule
Groups
Investigational
Description

Faropenem medoxomil is an ester prodrug derivative of the beta-lactam antibiotic faropenem. The prodrug form of faropenem offers dramatically improved oral bioavailability and leads to higher systemic concentrations of the drug. Faropenem medoxomil is a broad-spectrum antibiotic that is highly resistant to beta-lactamase degradation. It is being developed jointly by Replidyne, Inc. and Forest Laboratories, Inc.

Structure
Thumb
Synonyms
  • Faropenem daloxate
  • Faropenem medoxil
  • Faropenem medoxomil
External IDs
A 0026 / A-0026 / A0026 / BAY-56-6854 / SUN-A0026
International/Other Brands
Orapem
Categories
UNII
5OK523O4FU
CAS number
141702-36-5
Weight
Average: 397.4
Monoisotopic: 397.083137279
Chemical Formula
C17H19NO8S
InChI Key
JQBKWZPHJOEQAO-DVPVEWDBSA-N
InChI
InChI=1S/C17H19NO8S/c1-7(19)11-14(20)18-12(13(27-15(11)18)9-4-3-5-23-9)16(21)24-6-10-8(2)25-17(22)26-10/h7,9,11,15,19H,3-6H2,1-2H3/t7-,9-,11+,15-/m1/s1
IUPAC Name
(5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[(2R)-oxolan-2-yl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
SMILES
[H][C@]12SC(=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(=O)OCC1=C(C)OC(=O)O1)[C@@]1([H])CCCO1

Pharmacology

Indication

Investigated for use/treatment in bacterial infection, bronchitis, otitis media, and pediatric indications.

Pharmacodynamics

Faropenem has demonstrated excellent in vitro activity against common respiratory pathogens, many aerobic gram-positive organisms, and anaerobes. Activity against gram-negative organisms is more reserved. In vivo data suggest that faropenem is efficacious in treating community-acquired infections including uncomplicated skin and skin structure infections; however, more data may help to characterize faropenem's place in antimicrobial therapy.

Mechanism of action

Like other beta-lactam antibiotics, faropenem acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. It does this by binding to and competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidogylcan synthesis.

TargetActionsOrganism
UPenicillin-binding protein 1ANot AvailableStreptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
UPenicillin-binding protein 2BNot AvailableStreptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
UPeptidoglycan synthase FtsINot AvailableEscherichia coli O157:H7
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
  • Gram-positive Bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Gettig JP, Crank CW, Philbrick AH: Faropenem medoxomil. Ann Pharmacother. 2008 Jan;42(1):80-90. Epub 2007 Dec 19. [PubMed:18094341]
  2. Schurek KN, Wiebe R, Karlowsky JA, Rubinstein E, Hoban DJ, Zhanel GG: Faropenem: review of a new oral penem. Expert Rev Anti Infect Ther. 2007 Apr;5(2):185-98. [PubMed:17402834]
External Links
PubChem Compound
6918218
PubChem Substance
175427025
ChemSpider
5293428
ChEBI
134710
ChEMBL
CHEMBL1257070
Wikipedia
Faropenem

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentOtitis Media (OM)1
3TerminatedTreatmentChronic Bronchitis1

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 Solubility1.18 mg/mLALOGPS
logP0.64ALOGPS
logP0.23ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)14.85ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area111.6 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity95.39 m3·mol-1ChemAxon
Polarizability38.63 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7489
Blood Brain Barrier-0.8881
Caco-2 permeable-0.5799
P-glycoprotein substrateSubstrate0.5766
P-glycoprotein inhibitor INon-inhibitor0.7197
P-glycoprotein inhibitor IINon-inhibitor0.9655
Renal organic cation transporterNon-inhibitor0.8901
CYP450 2C9 substrateNon-substrate0.7947
CYP450 2D6 substrateNon-substrate0.8009
CYP450 3A4 substrateSubstrate0.5586
CYP450 1A2 substrateNon-inhibitor0.6407
CYP450 2C9 inhibitorNon-inhibitor0.6173
CYP450 2D6 inhibitorNon-inhibitor0.8494
CYP450 2C19 inhibitorNon-inhibitor0.5615
CYP450 3A4 inhibitorNon-inhibitor0.7569
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.757
Ames testNon AMES toxic0.724
CarcinogenicityNon-carcinogens0.8605
BiodegradationNot ready biodegradable0.6121
Rat acute toxicity2.3262 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9881
hERG inhibition (predictor II)Non-inhibitor0.8275
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 alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Penems / Thiazolecarboxylic acids and derivatives / Vinylogous thioesters / Carbonic acid diesters / Enoate esters / Heteroaromatic compounds / Tertiary carboxylic acid amides / Tetrahydrofurans / Thiazolines / Azetidines
show 12 more
Substituents
Alpha-amino acid or derivatives / Penem / Thiazolecarboxylic acid or derivatives / Carbonic acid diester / Vinylogous thioester / Beta-lactam / Tertiary carboxylic acid amide / Tetrahydrofuran / Thiazole / Meta-thiazoline
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Pharmacological action
Unknown
General Function
Penicillin binding
Specific Function
Cell wall formation.
Gene Name
ponA
Uniprot ID
Q04707
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
79757.96 Da
References
  1. Dalhoff A, Nasu T, Okamoto K: Target affinities of faropenem to and its impact on the morphology of gram-positive and gram-negative bacteria. Chemotherapy. 2003 Jul;49(4):172-83. [PubMed:12886052]
Kind
Protein
Organism
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Pharmacological action
Unknown
General Function
Penicillin binding
Specific Function
Not Available
Gene Name
penA
Uniprot ID
P0A3M5
Uniprot Name
Penicillin-binding protein 2B
Molecular Weight
73872.305 Da
References
  1. Dalhoff A, Nasu T, Okamoto K: Target affinities of faropenem to and its impact on the morphology of gram-positive and gram-negative bacteria. Chemotherapy. 2003 Jul;49(4):172-83. [PubMed:12886052]
Kind
Protein
Organism
Escherichia coli O157:H7
Pharmacological action
Unknown
General Function
Catalyzes cross-linking of the peptidoglycan cell wall at the division septum.
Specific Function
Penicillin binding
Gene Name
ftsI
Uniprot ID
P0AD69
Uniprot Name
Peptidoglycan D,D-transpeptidase FtsI
Molecular Weight
63876.925 Da
References
  1. Dalhoff A, Nasu T, Okamoto K: Target affinities of faropenem to and its impact on the morphology of gram-positive and gram-negative bacteria. Chemotherapy. 2003 Jul;49(4):172-83. [PubMed:12886052]

Drug created on November 18, 2007 11:26 / Updated on June 04, 2019 06:19