You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameAmdinocillin
Accession NumberDB01163  (APRD00789)
TypeSmall Molecule
GroupsWithdrawn
DescriptionAmidinopenicillanic 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
Thumb
Synonyms
Mecillinam
Penicillin HX
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CoactinNot Available
SelexidLeo
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIV10579P3QZ
CAS number32887-01-7
WeightAverage: 325.426
Monoisotopic: 325.146012307
Chemical FormulaC15H23N3O3S
InChI KeyBWWVAEOLVKTZFQ-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
IndicationUsed 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.
Structured Indications Not Available
PharmacodynamicsAmdinocillin 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 actionAmdinocillin 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Penicillin-binding protein 2aProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)Q8DNB6 details
Penicillin-binding protein 2Proteinyes
inhibitor
Escherichia coli (strain K12)P0AD65 details
Penicillin-binding protein 3Proteinyes
inhibitor
Streptococcus pneumoniaeQ75Y35 details
Penicillin-binding protein 1AProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)Q8DR59 details
Penicillin-binding protein 2BProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)P0A3M6 details
Penicillin-binding protein 1bProteinyes
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)Q7CRA4 details
Related Articles
AbsorptionPoorly absorbed if given orally.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeApproximately 1 hour in patients with normal renal function. Increases to 3 to 6 hours in anephric patients.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Gram-negative Bacteria
  • Staphylococcus saprophyticus
  • Escherichia coli
  • Proteus mirabilis
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcenocoumarolAmdinocillin may increase the anticoagulant activities of Acenocoumarol.Approved
AclarubicinThe serum concentration of Aclarubicin can be decreased when it is combined with Amdinocillin.Investigational
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Amdinocillin.Approved, Vet Approved
AmrubicinThe serum concentration of Amrubicin can be decreased when it is combined with Amdinocillin.Approved, Investigational
annamycinThe serum concentration of annamycin can be decreased when it is combined with Amdinocillin.Investigational
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Amdinocillin.Experimental, Vet Approved
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Amdinocillin.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Amdinocillin.Investigational
ChlortetracyclineThe therapeutic efficacy of Amdinocillin can be decreased when used in combination with Chlortetracycline.Approved, Vet Approved
DaunorubicinThe serum concentration of Daunorubicin can be decreased when it is combined with Amdinocillin.Approved
DemeclocyclineThe therapeutic efficacy of Amdinocillin can be decreased when used in combination with Demeclocycline.Approved
DicoumarolAmdinocillin may increase the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinThe serum concentration of Dihydrostreptomycin can be decreased when it is combined with Amdinocillin.Vet Approved
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Amdinocillin.Approved, Investigational
DoxycyclineThe therapeutic efficacy of Amdinocillin can be decreased when used in combination with Doxycycline.Approved, Investigational, Vet Approved
EpirubicinThe serum concentration of Epirubicin can be decreased when it is combined with Amdinocillin.Approved
Ethyl biscoumacetateAmdinocillin may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneAmdinocillin may increase the anticoagulant activities of Fluindione.Investigational
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Amdinocillin.Approved
GeneticinThe serum concentration of Geneticin can be decreased when it is combined with Amdinocillin.Experimental
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Amdinocillin.Approved, Vet Approved
GENTAMICIN C1AThe serum concentration of GENTAMICIN C1A can be decreased when it is combined with Amdinocillin.Experimental
Hygromycin BThe serum concentration of Hygromycin B can be decreased when it is combined with Amdinocillin.Vet Approved
IdarubicinThe serum concentration of Idarubicin can be decreased when it is combined with Amdinocillin.Approved
INNO-206The serum concentration of INNO-206 can be decreased when it is combined with Amdinocillin.Investigational
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Amdinocillin.Approved, Vet Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Amdinocillin.Approved
MetrizamideThe serum concentration of Metrizamide can be decreased when it is combined with Amdinocillin.Approved
MinocyclineThe therapeutic efficacy of Amdinocillin can be decreased when used in combination with Minocycline.Approved, Investigational
Mycophenolic acidThe serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Amdinocillin resulting in a loss in efficacy.Approved
NeamineThe serum concentration of Neamine can be decreased when it is combined with Amdinocillin.Experimental
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Amdinocillin.Approved, Vet Approved
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Amdinocillin.Approved
OxytetracyclineThe therapeutic efficacy of Amdinocillin can be decreased when used in combination with Oxytetracycline.Approved, Vet Approved
ParomomycinThe serum concentration of Paromomycin can be decreased when it is combined with Amdinocillin.Approved, Investigational
PhenindioneAmdinocillin may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonAmdinocillin may increase the anticoagulant activities of Phenprocoumon.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Amdinocillin.Approved
PirarubicinThe serum concentration of Pirarubicin can be decreased when it is combined with Amdinocillin.Investigational
PlicamycinThe serum concentration of Plicamycin can be decreased when it is combined with Amdinocillin.Approved, Withdrawn
ProbenecidThe serum concentration of Amdinocillin can be increased when it is combined with Probenecid.Approved
PuromycinThe serum concentration of Puromycin can be decreased when it is combined with Amdinocillin.Experimental
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Amdinocillin.Approved
SisomicinThe serum concentration of Sisomicin can be decreased when it is combined with Amdinocillin.Investigational
SP1049CThe serum concentration of SP1049C can be decreased when it is combined with Amdinocillin.Investigational
SpectinomycinThe serum concentration of Spectinomycin can be decreased when it is combined with Amdinocillin.Approved, Vet Approved
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Amdinocillin.Approved, Vet Approved
StreptozocinThe serum concentration of Streptozocin can be decreased when it is combined with Amdinocillin.Approved
TetracyclineThe therapeutic efficacy of Amdinocillin can be decreased when used in combination with Tetracycline.Approved, Vet Approved
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Amdinocillin.Approved, Investigational
ValrubicinThe serum concentration of Valrubicin can be decreased when it is combined with Amdinocillin.Approved
WarfarinAmdinocillin may increase the anticoagulant activities of Warfarin.Approved
ZorubicinThe serum concentration of Zorubicin can be decreased when it is combined with Amdinocillin.Experimental
Food InteractionsNot Available
References
Synthesis Reference

U.S. Patent 3,957,764.

General References
  1. 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
ATC CodesJ01CA11
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (42.1 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8439
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6287
P-glycoprotein substrateSubstrate0.7402
P-glycoprotein inhibitor INon-inhibitor0.6666
P-glycoprotein inhibitor IINon-inhibitor0.9677
Renal organic cation transporterNon-inhibitor0.7438
CYP450 2C9 substrateNon-substrate0.7291
CYP450 2D6 substrateNon-substrate0.779
CYP450 3A4 substrateSubstrate0.5355
CYP450 1A2 substrateNon-inhibitor0.8467
CYP450 2C9 inhibitorNon-inhibitor0.8666
CYP450 2D6 inhibitorNon-inhibitor0.9033
CYP450 2C19 inhibitorNon-inhibitor0.7809
CYP450 3A4 inhibitorNon-inhibitor0.8914
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9761
Ames testNon AMES toxic0.7016
CarcinogenicityNon-carcinogens0.8428
BiodegradationNot ready biodegradable0.5648
Rat acute toxicity1.5443 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9958
hERG inhibition (predictor II)Non-inhibitor0.7974
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 Properties
PropertyValueSource
melting point156 dec °CPhysProp
water solubility0.0103 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP1.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.979 mg/mLALOGPS
logP1.41ALOGPS
logP-0.55ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)3.3ChemAxon
pKa (Strongest Basic)7.92ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area73.21 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity84.31 m3·mol-1ChemAxon
Polarizability34.18 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Penam
  • Azepane
  • Thiazolidine
  • Tertiary carboxylic acid amide
  • Beta-lactam
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Organoheterocyclic compound
  • Dialkylthioether
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Hemithioaminal
  • Thioether
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid amidine
  • Amidine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors

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
Molecular Weight:
80797.94 Da
References
  1. 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
Molecular Weight:
70856.1 Da
References
  1. 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 ]
  2. 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
Molecular Weight:
45209.84 Da
References
  1. 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
Molecular Weight:
79700.9 Da
References
  1. 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:
Not Available
Gene Name:
penA
Uniprot ID:
P0A3M6
Molecular Weight:
73872.305 Da
References
  1. 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
Molecular Weight:
89479.92 Da
References
  1. 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 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23