Details
Stereochemistry | RACEMIC |
Molecular Formula | C19H22N4O3 |
Molecular Weight | 354.403 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(CC2=C(N)N=C(N)N=C2)=C3C=CC(OC3=C1OC)C4CC4
InChI
InChIKey=HWJPWWYTGBZDEG-UHFFFAOYSA-N
InChI=1S/C19H22N4O3/c1-24-15-8-11(7-12-9-22-19(21)23-18(12)20)13-5-6-14(10-3-4-10)26-16(13)17(15)25-2/h5-6,8-10,14H,3-4,7H2,1-2H3,(H4,20,21,22,23)
Iclaprim is an investigational broad-spectrum diaminopyrimidine antibiotic in development for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Iclaprim acts on bacterial cells by competitively inhibiting dihydrofolate reductase (DHFR), a key enzyme in the folate cycle; the same mode of inhibition is exerted by trimethoprim. Iclaprim resistance is mainly determined by point mutations in the dfr gene as studied in S. aureus and S. pneumoniae. Surveillance studies demonstrate that the spectrum of activity of iclaprim includes many
organisms indicated in cSSSI including S. aureus and S. pyogenes. Iclaprim is bactericidal in vitro, generally at concentrations equal to the MIC that are maintained in human plasma for several hours after a therapeutic dose. Bactericidal activity is primarily time-dependent and concentration independent. Due to its structural similarity with trimethoprim, iclaprim is synergistic with
sulfonamides against a broad spectrum of bacterial species. The antimicrobial mechanism of action of iclaprim is mediated by competitive inhibition of
bacterial DHFR, the same mode of inhibition exerted by TMP. The activity of iclaprim against TMP-R mutants of S. aureus and S. pneumoniae is attributable to additional hydrophobic interaction between iclaprim and the enzyme. The same mechanism of action of iclaprim, competitive inhibition with the natural substrate DHF, is seen against both TMP-S and -R enzymes. Iclaprim is well suited for use as a first-line empiric monotherapy in patients with ABSSSI who are comorbid with renal impairment for the following reasons. n July 2015, the U.S. Food and Drug Administration, or FDA, designated the IV formulation of iclaprim as a Qualified Infectious Disease Product (QIDP) for ABSSSI and HABP. QIDP status grants iclaprim regulatory Fast Track designation, Priority Review and, if approved, a five-year extension to the statutory market exclusivity period in the United States, resulting in 10 years of market exclusivity from the date of approval.
Originator
Approval Year
PubMed
Title | Date | PubMed |
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Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. | 2003 Dec 1 |
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Effect of human plasma on the antimicrobial activity of iclaprim in vitro. | 2007 Dec |
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Iclaprim. | 2007 Sep |
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Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men. | 2007 Sep |
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Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic-resistant staphylococcal infections. | 2008 Feb |
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Inhibitory properties and X-ray crystallographic study of the binding of AR-101, AR-102 and iclaprim in ternary complexes with NADPH and dihydrofolate reductase from Staphylococcus aureus. | 2009 Aug |
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New antibiotics for healthcare-associated pneumonia. | 2009 Feb |
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Treatments for skin and soft-tissue and surgical site infections due to MDR Gram-positive bacteria. | 2009 Sep |
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[Update on antimicrobial chemotherapy]. | 2010 Mar |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02600611
Skin Structures and Soft Tissue Infections treatment: Iclaprim 80 mg intravenous every 12 hours
Route of Administration:
Intravenous
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C2153
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Iclaprim
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)