Iclaprim

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Systematic (IUPAC) name
(RS)-5-[(2- cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)methyl]pyrimidine-2,4-diamine
Clinical data
Legal status	Investigational
Routes of administration	Oral, intravenous
Pharmacokinetic data
Bioavailability	Good (oral)
Identifiers
CAS Number	192314-93-5 Y
ATC code	J01EA03 (WHO)
PubChem	CID: 213043
ChemSpider	184736 N
UNII	42445HUU0O N
KEGG	D08337 Y
ChEBI	CHEBI:131724
ChEMBL	CHEMBL134561 N
Chemical data
Formula	C19H22N4O3
Molecular mass	354.403 g/mol
SMILES COC1=C(C2=C(C=CC(O2)C3CC3)C(=C1)CC4=CN=C(N=C4N)N)OC
InChI 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) N Key:HWJPWWYTGBZDEG-UHFFFAOYSA-N N
NY (what is this?)  (verify)

Iclaprim (INN), codenamed AR-100 and RO-48-2622, is a diaminopyrimidine dihydrofolate reductase (DHFR)-inhibiting extended-spectrum antibiotic active against gram positive organisms being developed for the treatment of complicated skin and soft tissue infections caused by antibiotic-resistant bacteria. It is structurally related to trimethoprim. In Phase III clinical trials, intravenously-administered iclaprim was found to be as effective as and better tolerated than linezolid in people with skin and soft tissue infections, many caused by methicillin-resistant Staphylococcus aureus (MRSA). In vitro, iclaprim is highly active against MRSA, vancomycin-resistant Staphylococcus aureus (VRSA), strains of Streptococcus pneumoniae resistant to several common antibiotics, and some Gram-negative bacteria.

A new drug application for iclaprim was filed with the U.S. Food and Drug Administration in March 2008, and a marketing authorisation application (MAA) was accepted by the European Medicines Agency on August 21, 2008. Phase II clinical trials are being conducted to assess whether iclaprim can be taken by mouth as well as intravenously and whether it is effective for the treatment of hospital-acquired pneumonia.

Iclaprim was granted fast track status by the FDA, but approval of the drug was eventually declined in 2009 and no further development has taken place since then.

In Jan 2015, Motif BioSciences gained rights to iclaprim and planned to continue its development. In 2016 phase 3 trials began.

File:Staphylococcus aureus F98Y DHFR complexed with iclaprim and NADPH.gif

Iclaprim & NADPH bound to DHFR. PDB entry: 3FRA. The different amino acids are color coded.