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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
Structure of ICLAPRIM MESYLATE

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)

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Alternatives to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.
2007 Sep 15
Investigational antimicrobial drugs for bloodstream infections.
2008 Aug
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
Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic-resistant staphylococcal infections.
2008 Feb
Gateways to clinical trials.
2008 Oct
New antimicrobial molecules and new antibiotic strategies.
2009 Apr
Antimicrobial development in the era of emerging resistance.
2009 Jul
Treatments for skin and soft-tissue and surgical site infections due to MDR Gram-positive bacteria.
2009 Sep
Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options.
2010 Nov
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 Fri Dec 15 16:31:27 GMT 2023
Edited
by admin
on Fri Dec 15 16:31:27 GMT 2023
Record UNII
7U972CJ5AT
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ICLAPRIM MESYLATE
DASH   USAN  
USAN  
Official Name English
ICLAPRIM MESILATE [MART.]
Common Name English
ICLAPRIM MESYLATE [USAN]
Common Name English
5-[[(2RS)-2-Cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-yl]methyl]pyrimidine-2,4-diamine methanesulfonate
Systematic Name English
ICLAPRIMMONOMESILATE
WHO-DD  
Common Name English
2,4-PYRIMIDINEDIAMINE, 5-((2-CYCLOPROPYL-7,8-DIMETHOXY-2H-1-BENZOPYRAN-5-YL)METHYL)-, MONOMETHANESULFONATE
Systematic Name English
2,4-PYRIMIDINEDIAMINE, 5-((2-CYCLOPROPYL-7,8-DIMETHOXY-2H-1-BENZOPYRAN-5-YL)METHYL)-, MONOMETHANESULPHONATE
Systematic Name English
Iclaprimmonomesilate [WHO-DD]
Common Name English
ICLAPRIM METHANESULFONATE [MI]
Common Name English
ICLAPRIM MESILATE
MART.  
Common Name English
AR-100001
Code English
Code System Code Type Description
FDA UNII
7U972CJ5AT
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
PUBCHEM
24785689
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
SMS_ID
100000092701
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
NCI_THESAURUS
C167047
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
DRUG BANK
DBSALT002008
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
MERCK INDEX
m6196
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY Merck Index
EVMPD
SUB28993
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
CAS
474793-41-4
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
EPA CompTox
DTXSID10963854
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
ChEMBL
CHEMBL134561
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
USAN
UU-22
Created by admin on Fri Dec 15 16:31:27 GMT 2023 , Edited by admin on Fri Dec 15 16:31:27 GMT 2023
PRIMARY
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ACTIVE MOIETY