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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
Structure of ICLAPRIM

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)

HIDE SMILES / InChI

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.6 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria.
2003 Dec 1
Recently approved and investigational antibiotics for treatment of severe infections caused by Gram-positive bacteria.
2005 Oct
Infections associated with orthopedic implants.
2006 Aug
Antibacterial drug discovery and development--SRI's 11th Annual Summit. Antibacterial trends and current research.
2006 Jun
Dihydrofolate reductase inhibitors as antibacterial agents.
2006 Mar 30
Gateways to clinical trials.
2007 Dec
In vitro activity of the novel diaminopyrimidine, iclaprim, in combination with folate inhibitors and other antimicrobials with different mechanisms of action.
2007 Dec
Effect of human plasma on the antimicrobial activity of iclaprim in vitro.
2007 Dec
Investigational treatments for postoperative surgical site infections.
2007 Feb
Activity of iclaprim against Legionella pneumophila.
2007 Oct
Iclaprim.
2007 Sep
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
Alternatives to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.
2007 Sep 15
Current and novel antibiotics against resistant Gram-positive bacteria.
2008
[New antimicrobials against Gram-positive organisms].
2008
Investigational antimicrobial drugs for bloodstream infections.
2008 Aug
What's new and not so new on the antimicrobial horizon?
2008 Dec
A review of telavancin in the treatment of complicated skin and skin structure infections (cSSSI).
2008 Feb
Pharmacologic options for CNS infections caused by resistant Gram-positive organisms.
2008 Feb
Gateways to clinical trials.
2008 Jun
Gateways to clinical trials.
2008 Oct
Evidence based approach to the treatment of community-associated methicillin-resistant Staphylococcus aureus.
2009
The determinants of the antibiotic resistance process.
2009
Bench-to-bedside review: Understanding the impact of resistance and virulence factors on methicillin-resistant Staphylococcus aureus infections in the intensive care unit.
2009
Increased hydrophobic interactions of iclaprim with Staphylococcus aureus dihydrofolate reductase are responsible for the increase in affinity and antibacterial activity.
2009 Apr
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
New antimicrobial agents for methicillin-resistant Staphylococcus aureus.
2009 Dec
Future treatment options for Gram-positive infections--looking ahead.
2009 Dec
New antibiotics for healthcare-associated pneumonia.
2009 Feb
Activity of iclaprim against clinical isolates of Streptococcus pyogenes and Streptococcus agalactiae.
2009 Feb
Regulatory watch: Non-inferiority-trial discussions impact new drug applications.
2009 Jan
Iclaprim, a novel diaminopyrimidine for the treatment of resistant gram-positive infections.
2009 Jun
New antibiotics for antibiotic-resistant bacteria.
2009 May 28
[New antibiotics: small or big advances?].
2009 Oct
New treatments for methicillin-resistant Staphylococcus aureus.
2009 Oct
Treatments for skin and soft-tissue and surgical site infections due to MDR Gram-positive bacteria.
2009 Sep
Enantioselective synthesis of iclaprim enantiomers--a versatile approach to 2-substituted chiral chromenes.
2010 Jun 4
[Update on antimicrobial chemotherapy].
2010 Mar
Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options.
2010 Nov
Mechanisms of resistance to antimicrobial drugs in pathogenic Gram-positive cocci.
2010 Sep
Patents

Patents

Sample Use Guides

Skin Structures and Soft Tissue Infections treatment: Iclaprim 80 mg intravenous every 12 hours
Route of Administration: Intravenous
Against both MSSA and MRSA isolates, the MIC50 and MIC90 of iclaprim were 0.06 and 0.12 ug/mL, respectively. Iclaprim had variable activity against VISA and VRSA strains; iclaprim MICs ranged from 0.06 to > 8 ug/mL for 6 hVISA/VISA and VRSA isolates.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:35:24 GMT 2023
Edited
by admin
on Sat Dec 16 17:35:24 GMT 2023
Record UNII
42445HUU0O
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ICLAPRIM
INN   MART.   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
2,4-PYRIMIDINEDIAMINE, 5-((2-CYCLOPROPYL-7,8-DIMETHOXY-2H-1-BENZOPYRAN-5-YL)METHYL)-
Systematic Name English
ICLAPRIM [MART.]
Common Name English
RO-48-2622
Code English
AR-100.001
Code English
5-{[(2RS)-2-Cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-yl]methyl}pyrimidine-2,4-diamine
Systematic Name English
Iclaprim [WHO-DD]
Common Name English
ICLAPRIM [USAN]
Common Name English
AR-100
Code English
iclaprim [INN]
Common Name English
RO 48-2622
Code English
ICLAPRIM [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C258
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
WHO-ATC J01EA03
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
FDA ORPHAN DRUG 514415
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
WHO-VATC QJ01EA03
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
NCI_THESAURUS C2153
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
Code System Code Type Description
FDA UNII
42445HUU0O
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
INN
8315
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
EPA CompTox
DTXSID70870191
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
ChEMBL
CHEMBL134561
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
EVMPD
SUB32201
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
DRUG CENTRAL
4573
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
NCI_THESAURUS
C65877
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
CAS
192314-93-5
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
PUBCHEM
213043
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
MERCK INDEX
m6196
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY Merck Index
USAN
UU-105
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
DRUG BANK
DB06358
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
SMS_ID
100000124368
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
WIKIPEDIA
Iclaprim
Created by admin on Sat Dec 16 17:35:24 GMT 2023 , Edited by admin on Sat Dec 16 17:35:24 GMT 2023
PRIMARY
Related Record Type Details
ENANTIOMER -> RACEMATE
TARGET ORGANISM->INHIBITOR
ENANTIOMER -> RACEMATE
TARGET ORGANISM->INHIBITOR
SALT/SOLVATE -> PARENT
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ACTIVE MOIETY