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)
Molecular Formula | C19H22N4O3 |
Molecular Weight | 354.403 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
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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Recently approved and investigational antibiotics for treatment of severe infections caused by Gram-positive bacteria. | 2005 Oct |
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Infections associated with orthopedic implants. | 2006 Aug |
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Antibacterial drug discovery and development--SRI's 11th Annual Summit. Antibacterial trends and current research. | 2006 Jun |
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Dihydrofolate reductase inhibitors as antibacterial agents. | 2006 Mar 30 |
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Gateways to clinical trials. | 2007 Dec |
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Effect of human plasma on the antimicrobial activity of iclaprim in vitro. | 2007 Dec |
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Investigational treatments for postoperative surgical site infections. | 2007 Feb |
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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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Current and novel antibiotics against resistant Gram-positive bacteria. | 2008 |
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[New antimicrobials against Gram-positive organisms]. | 2008 |
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What's new and not so new on the antimicrobial horizon? | 2008 Dec |
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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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Registered and investigational drugs for the treatment of methicillin-resistant Staphylococcus aureus infection. | 2008 Jan |
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Gateways to clinical trials. | 2008 Jun |
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Evidence based approach to the treatment of community-associated methicillin-resistant Staphylococcus aureus. | 2009 |
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The determinants of the antibiotic resistance process. | 2009 |
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Bench-to-bedside review: Understanding the impact of resistance and virulence factors on methicillin-resistant Staphylococcus aureus infections in the intensive care unit. | 2009 |
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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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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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Regulatory watch: Non-inferiority-trial discussions impact new drug applications. | 2009 Jan |
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Antimicrobial development in the era of emerging resistance. | 2009 Jul |
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Iclaprim, a novel diaminopyrimidine for the treatment of resistant gram-positive infections. | 2009 Jun |
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New antibiotics for antibiotic-resistant bacteria. | 2009 May 28 |
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[New antibiotics: small or big advances?]. | 2009 Oct |
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New treatments for methicillin-resistant Staphylococcus aureus. | 2009 Oct |
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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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Enantioselective synthesis of iclaprim enantiomers--a versatile approach to 2-substituted chiral chromenes. | 2010 Jun 4 |
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Mechanisms of resistance to antimicrobial drugs in pathogenic Gram-positive cocci. | 2010 Sep |
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
Substance Class |
Chemical
Created
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admin
on
Edited
Thu Jul 06 22:57:17 UTC 2023
by
admin
on
Thu Jul 06 22:57:17 UTC 2023
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Record UNII |
42445HUU0O
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Validated (UNII)
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NCI_THESAURUS |
C258
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J01EA03
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514415
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QJ01EA03
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NCI_THESAURUS |
C2153
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Iclaprim
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Related Record | Type | Details | ||
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ENANTIOMER -> RACEMATE |
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TARGET ORGANISM->INHIBITOR |
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ENANTIOMER -> RACEMATE |
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TARGET ORGANISM->INHIBITOR |
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ACTIVE MOIETY |
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