Iclaprim

Structural formula
	Structural formula without stereochemistry
General
Non-proprietary name	Iclaprim
other names	( RS ) -5 - [(2-Cyclopropyl-7,8-dimethoxy-2 H -chromen-5-yl) methyl] pyrimidine-2,4-diamine IUPAC ; Iclaprimum Latin ; AR-100; Ro-48-2622;
Molecular formula	C 19 H 22 N 4 O 3 (iclaprim) ; C 20 H 26 N 4 O 6 S (iclaprim mesilate) ;
External identifiers / databases
EC number	606-269-6
ECHA InfoCard	100.130.860
PubChem	213043
ChemSpider	184736
DrugBank	DB06358
Wikidata	Q907480
Drug information
ATC code	J01 EA03
Drug class	Antibiotics
Mechanism of action	Inhibition of bacterial dihydrofolate reductase
properties
Molar mass	354.40 g · mol -1 (iclaprim) ; 450,51 g · mol -1 (iclaprim · mesylate) ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 361
	P: 280-308 + 313
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Iclaprim (intended trade name Iclaprim Arpida ^® ; manufacturer Arpida ) is an antibiotic and belongs to the group of diaminopyrimidines . Iclaprim is in the approval process and is to be approved for the treatment of complex skin and skin structure infections (cSSSI).

Clinical information

Areas of application and spectrum of activity

Iclaprim is an antibiotic and belongs to the group of diaminopyrimidines . It acts as a potent inhibitor of bacterial dihydrofolate reductase , like trimethoprim , another representative of this class of substances. Iclaprim, on the other hand, is still effective against many trimethoprim-resistant pathogen strains. In in vitro studies , Iclaprim shows a high level of effectiveness against the most clinically relevant gram-positive bacteria . The spectrum of activity includes resistant strains isolated from patients with severe MRSA and VRSA infections. Opposite anaerobes Iclaprim shows little effect.

Spectrum of sensitive germs

Staphylococci , including Staphylococcus aureus including multi-resistant strains (MRSA),
Enterococci including vancomycin-resistant strains (VRE),
Streptococci including penicillin-resistant strains.

Clinical application

Iclaprim is to be approved for the treatment of complex skin and skin structure infections (cSSSI).

Pharmacological properties

Mechanism of action (pharmacodynamics)

Iclaprim works by inhibiting bacterial dihydrofolate reductase without significantly inhibiting the human enzyme. As a result, there is an inhibition of the synthesis of DNA building blocks and cell death.

Absorption and distribution in the body (pharmacokinetics)

In clinical trials, Iclaprim is given either intravenously or orally . When administered orally, the bioavailability is about 40%. With the recommended dose of 160 mg and oral administration, the maximum plasma level of 0.5 µg / ml is reached 90 minutes after ingestion. With intravenous administration of 0.4 and 0.8 mg / kg body weight, plasma concentrations of 0.37 and 0.87 µg / ml are achieved. The plasma half-life is about two hours.

Other Information

Iclaprim was in the fast-track approval process of the American Food and Drug Administration (FDA); approval was not granted for the time being in January 2009.

Stereochemistry

Iclaprim contains a stereocenter and consists of two enantiomers. This is a racemate , i.e. a 1: 1 mixture of ( R ) - and ( S ) -form:

Enantiomers of phantolide
CAS number: 1208116-65-7	CAS number: 1208116-66-8

literature

Ernst Mutschler among others: Mutschler - drug effects textbook of pharmacology and toxicology . 9th edition. Scientific Verlagsgesellschaft, Stuttgart 2008, ISBN 978-3-8047-1952-1 .
P. Schneider, S. Hawser, K. Islam: Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria . In: Bioorg Med Chem Lett . tape 13 , no. December 23 , 2003, pp. 4217-4221 , PMID 14623005 ( tufts.edu [PDF]).

A. Morgan, C. Cofer, DL Stevens: Iclaprim: a novel dihydrofolate reductase inhibitor for skin and soft tissue infections. In: Future Microbiol. 4, March 2009, pp. 131-144, PMID 19257839 , doi: 10.2217 / 17460913.4.2.131 .

Individual evidence

↑ ^a ^b Registration dossier on 2,4-Pyrimidinediamine, 5 - [(2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-yl) methyl] - ( GHS section ) at the European Chemicals Agency (ECHA), accessed on June 10, 2020.
↑ WJ Peppard, CD Schuenke: Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic-resistant staphylococcal infections . In: Curr Opin Investig Drugs . tape 9 , no. 2 , February 2008, p. 210-25 , PMID 18246524 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Dihydrofolate Reductase - Learning and Teaching Materials

Staphylococci and MRSA - information from the Robert Koch Institute

[Registrierungsdossier-1] Registration dossier on 2,4-Pyrimidinediamine, 5 - [(2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-yl) methyl] - ( GHS section ) at the European Chemicals Agency (ECHA), accessed on June 10, 2020.

[2] WJ Peppard, CD Schuenke: Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic-resistant staphylococcal infections . In: Curr Opin Investig Drugs . tape 9 , no. 2 , February 2008, p. 210-25 , PMID 18246524 .