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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyAmdinocillin
Identification
- Name
- Amdinocillin
- Accession Number
- DB01163 (APRD00789)
- Type
- Small Molecule
- Groups
- Investigational, Withdrawn
- Description
Amidinopenicillanic acid derivative with broad spectrum antibacterial action. It is poorly absorbed if given orally and is used in urinary infections and typhus. Amdinocillin is not available in the United States.
- Structure
Structure for Amdinocillin (DB01163)
- Synonyms
- Amdinocillin
- Mecilinamo
- Mecillinam
- Mecillinamum
- Penicillin HX
- External IDs
- FL 1060 / FL-1060 / RO 10-9070 / RO-10-9070
- International/Other Brands
- Coactin / Selexid (Leo)
- Categories
- Amides
- Anti-Bacterial Agents
- Anti-Infective Agents
- Anti-Infective Agents, Urinary
- Antibacterials for Systemic Use
- Antiinfectives for Systemic Use
- Beta-Lactam Antibacterials
- beta-Lactams
- Heterocyclic Compounds, Fused-Ring
- Lactams
- Penicillins
- Penicillins With Extended Spectrum
- Renal Agents
- Sulfur Compounds
- UNII
- V10579P3QZ
- CAS number
- 32887-01-7
- Weight
- Average: 325.426
Monoisotopic: 325.146012307 - Chemical Formula
- C15H23N3O3S
- InChI Key
- BWWVAEOLVKTZFQ-ISVUSNJMSA-N
- InChI
- InChI=1S/C15H23N3O3S/c1-15(2)11(14(20)21)18-12(19)10(13(18)22-15)16-9-17-7-5-3-4-6-8-17/h9-11,13H,3-8H2,1-2H3,(H,20,21)/b16-9+/t10-,11+,13-/m1/s1
- IUPAC Name
- (2S,5R,6R)-6-[(azepan-1-ylmethylidene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
- SMILES
- [H]C(=N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@]12[H])N1CCCCCC1
Pharmacology
- Indication
Used in the treatment of urinary tract infections caused by some strains of E. coli and klebsiella and enterobacter species. Used mainly against Gram negative organisms.
- Pharmacodynamics
Amdinocillin is a novel, semisynthetic penicillin effective against many gram-negative bacteria. The antibacterial activity of amdinocillin is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Co-administration of probenecid results in markedly elevated plasma levels of amdinocillin and delays its excretion.
- Mechanism of action
Amdinocillin is a stong and specific antagonist of Penicillin Binding Protein-2 (PBP 2). It is active against gram negative bacteria, preventing cell wall synthesis by inhibiting the activity of PBP2. PBP2 is a peptidoglycan elongation initiating enzyme. Peptidoglycan is a polymer of sugars and amino acids that is the main component of bacterial cell walls.
Target Actions Organism APenicillin-binding protein 2a inhibitorStreptococcus pneumoniae (strain ATCC BAA-255 / R6) APenicillin-binding protein 2 inhibitorEscherichia coli (strain K12) APenicillin-binding protein 3 inhibitorStreptococcus pneumoniae APenicillin-binding protein 1A inhibitorStreptococcus pneumoniae (strain ATCC BAA-255 / R6) APenicillin-binding protein 2B inhibitorStreptococcus pneumoniae (strain ATCC BAA-255 / R6) APenicillin-binding protein 1b inhibitorStreptococcus pneumoniae (strain ATCC BAA-255 / R6) - Absorption
Poorly absorbed if given orally.
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
- Not Available
- Half life
Approximately 1 hour in patients with normal renal function. Increases to 3 to 6 hours in anephric patients.
- Clearance
- Not Available
- Toxicity
- Not Available
- Affected organisms
- Gram-negative Bacteria
- Staphylococcus saprophyticus
- Escherichia coli
- Proteus mirabilis
- 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.
Drug Interaction Unlock Additional Data(R)-warfarin Amdinocillin may increase the anticoagulant activities of (R)-warfarin. (S)-Warfarin Amdinocillin may increase the anticoagulant activities of (S)-Warfarin. 4-hydroxycoumarin Amdinocillin may increase the anticoagulant activities of 4-hydroxycoumarin. Acemetacin Acemetacin may decrease the excretion rate of Amdinocillin which could result in a higher serum level. Acenocoumarol Amdinocillin may increase the anticoagulant activities of Acenocoumarol. Alcuronium The therapeutic efficacy of Alcuronium can be increased when used in combination with Amdinocillin. Amikacin The serum concentration of Amikacin can be decreased when it is combined with Amdinocillin. Apramycin The serum concentration of Apramycin can be decreased when it is combined with Amdinocillin. Arbekacin The serum concentration of Arbekacin can be decreased when it is combined with Amdinocillin. Atracurium The therapeutic efficacy of Atracurium can be increased when used in combination with Amdinocillin. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Not Available
References
- Synthesis Reference
U.S. Patent 3,957,764.
- General References
- Neu HC: Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death. Am J Med. 1983 Aug 29;75(2A):9-20. [PubMed:6311012]
- External Links
- KEGG Drug
- D02888
- PubChem Compound
- 36273
- PubChem Substance
- 46508450
- ChemSpider
- 33357
- RxNav
- 626
- ChEBI
- 51208
- ChEMBL
- CHEMBL530
- ZINC
- ZINC000003830206
- Therapeutic Targets Database
- DAP001176
- PharmGKB
- PA164754807
- Wikipedia
- Amdinocillin
- ATC Codes
- J01CA11 — Mecillinam
- MSDS
- Download (42.1 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Terminated Treatment Chlamydia Trachomatis Infection / Chlamydial Urethritis 1 4 Completed Treatment Acute Cystitis (Excl in Pregnancy) 1 4 Completed Treatment Pyelonephritis / Urinary Tract Infection 1 4 Recruiting Prevention Complications / Infection / Prostate Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 156 dec °C PhysProp water solubility 0.0103 mg/mL at 25 °C MEYLAN,WM et al. (1996) logP 1.3 Not Available - Predicted Properties
Property Value Source Water Solubility 0.979 mg/mL ALOGPS logP 1.41 ALOGPS logP -0.55 ChemAxon logS -2.5 ALOGPS pKa (Strongest Acidic) 3.3 ChemAxon pKa (Strongest Basic) 7.92 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 73.21 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 84.31 m3·mol-1 ChemAxon Polarizability 34.18 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption - 0.8439 Blood Brain Barrier - 0.9659 Caco-2 permeable - 0.6287 P-glycoprotein substrate Substrate 0.7402 P-glycoprotein inhibitor I Non-inhibitor 0.6666 P-glycoprotein inhibitor II Non-inhibitor 0.9677 Renal organic cation transporter Non-inhibitor 0.7438 CYP450 2C9 substrate Non-substrate 0.7291 CYP450 2D6 substrate Non-substrate 0.779 CYP450 3A4 substrate Substrate 0.5355 CYP450 1A2 substrate Non-inhibitor 0.8467 CYP450 2C9 inhibitor Non-inhibitor 0.8666 CYP450 2D6 inhibitor Non-inhibitor 0.9033 CYP450 2C19 inhibitor Non-inhibitor 0.7809 CYP450 3A4 inhibitor Non-inhibitor 0.8914 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9761 Ames test Non AMES toxic 0.7016 Carcinogenicity Non-carcinogens 0.8428 Biodegradation Not ready biodegradable 0.5648 Rat acute toxicity 1.5443 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9958 hERG inhibition (predictor II) Non-inhibitor 0.7974
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 LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-004i-0209000000-8ccc98a85688a2a0d3da
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
- Penams / Azepanes / Thiazolidines / Tertiary carboxylic acid amides / Azetidines / Azacyclic compounds / Thiohemiaminal derivatives / Propargyl-type 1,3-dipolar organic compounds / Carboxamidines / Monocarboxylic acids and derivatives show 8 more
- Substituents
- Alpha-amino acid or derivatives / Penam / Azepane / Beta-lactam / Tertiary carboxylic acid amide / Thiazolidine / Azetidine / Carboxamide group / Lactam / Amidine show 21 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- penicillin (CHEBI:51208)
Targets
- Kind
- Protein
- Organism
- Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transferase activity, transferring acyl groups
- Specific Function
- Not Available
- Gene Name
- pbp2a
- Uniprot ID
- Q8DNB6
- Uniprot Name
- Penicillin-binding protein 2a
- Molecular Weight
- 80797.94 Da
References
- Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type d-ala-d-ala carboxypeptidase activity
- Specific Function
- Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
- Gene Name
- mrdA
- Uniprot ID
- P0AD65
- Uniprot Name
- Penicillin-binding protein 2
- Molecular Weight
- 70856.1 Da
References
- Neu HC: Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death. Am J Med. 1983 Aug 29;75(2A):9-20. [PubMed:6311012]
- Licht J, Gally D, Henderson T, Young K, Cooper S: Effect of mecillinam on peptidoglycan synthesis during the division cycle of Salmonella typhimurium 2616. Res Microbiol. 1993 Jul-Aug;144(6):423-33. [PubMed:8190989]
- Kind
- Protein
- Organism
- Streptococcus pneumoniae
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type d-ala-d-ala carboxypeptidase activity
- Specific Function
- Not Available
- Gene Name
- pbp3
- Uniprot ID
- Q75Y35
- Uniprot Name
- Penicillin-binding protein 3
- Molecular Weight
- 45209.84 Da
References
- Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
- Kind
- Protein
- Organism
- Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Penicillin binding
- Specific Function
- Cell wall formation.
- Gene Name
- pbpA
- Uniprot ID
- Q8DR59
- Uniprot Name
- Penicillin-binding protein 1A
- Molecular Weight
- 79700.9 Da
References
- Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
- Kind
- Protein
- Organism
- Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- Penicillin binding
- Gene Name
- penA
- Uniprot ID
- P0A3M6
- Uniprot Name
- Penicillin-binding protein 2B
- Molecular Weight
- 73872.305 Da
References
- Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
- Kind
- Protein
- Organism
- Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Transferase activity, transferring acyl groups
- Specific Function
- Not Available
- Gene Name
- pbp1b
- Uniprot ID
- Q7CRA4
- Uniprot Name
- Penicillin-binding protein 1b
- Molecular Weight
- 89479.92 Da
References
- Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. [PubMed:7447421]
Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51
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