Details
Stereochemistry | RACEMIC |
Molecular Formula | C19H22N4O3.CH4O3S |
Molecular Weight | 450.509 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.COC1=CC(CC2=C(N)N=C(N)N=C2)=C3C=CC(OC3=C1OC)C4CC4
InChI
InChIKey=BQCQVDMEHSONNK-UHFFFAOYSA-N
InChI=1S/C19H22N4O3.CH4O3S/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;1-5(2,3)4/h5-6,8-10,14H,3-4,7H2,1-2H3,(H4,20,21,22,23);1H3,(H,2,3,4)
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 |
---|---|---|
Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. | 2003 Dec 1 |
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Dihydrofolate reductase inhibitors as antibacterial agents. | 2006 Mar 30 |
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In vitro activity of the novel diaminopyrimidine, iclaprim, in combination with folate inhibitors and other antimicrobials with different mechanisms of action. | 2007 Dec |
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Effect of human plasma on the antimicrobial activity of iclaprim in vitro. | 2007 Dec |
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Alternatives to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. | 2007 Sep 15 |
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Current and novel antibiotics against resistant Gram-positive bacteria. | 2008 |
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Investigational antimicrobial drugs for bloodstream infections. | 2008 Aug |
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A review of telavancin in the treatment of complicated skin and skin structure infections (cSSSI). | 2008 Feb |
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Registered and investigational drugs for the treatment of methicillin-resistant Staphylococcus aureus infection. | 2008 Jan |
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Gateways to clinical trials. | 2008 Oct |
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New antimicrobial molecules and new antibiotic strategies. | 2009 Apr |
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Increased hydrophobic interactions of iclaprim with Staphylococcus aureus dihydrofolate reductase are responsible for the increase in affinity and antibacterial activity. | 2009 Apr |
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New antimicrobial agents for methicillin-resistant Staphylococcus aureus. | 2009 Dec |
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[Update on antimicrobial chemotherapy]. | 2010 Mar |
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Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options. | 2010 Nov |
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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ACTIVE MOIETY
SUBSTANCE RECORD