Iclaprim
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MedKoo CAT#: 326859

CAS#: 192314-93-5

Description: Iclaprim, also known as AR-100; RO-48-2622; AR-100.001; RO-482622, 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 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.

Chemical Structure

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Iclaprim
CAS# 192314-93-5
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 326859
Name: Iclaprim
CAS#: 192314-93-5
Chemical Formula: C19H22N4O3
Exact Mass: 354.17
Molecular Weight: 354.410
Elemental Analysis: C, 64.39; H, 6.26; N, 15.81; O, 13.54

Price and Availability

Size Price Availability Quantity
1mg USD 380 2 Weeks
5mg USD 950 2 Weeks
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Synonym: AR-100; AR100; AR 100; RO-482622; RO 482622; RO482622; RO-48-2622; AR-100.001; Iclaprim.

IUPAC/Chemical Name: 5-((2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)methyl)pyrimidine-2,4-diamine

InChi Key: HWJPWWYTGBZDEG-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: NC1=NC=C(CC2=CC(OC)=C(OC)C3=C2C=CC(C4CC4)O3)C(N)=N1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
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Biological target: Iclaprim is a new selective bacterial Dihydrofolate inhibitor, which can inhibit the growth of S. aureus (MRSA) with an MIC90 of 0.06 μg/mL.
In vitro activity: Iclaprim, but not trimethoprim, potently increased expression of hla (Fig. 5c). However iclaprim was more effective at suppressing production of alpha haemolysin than the other antibiotics tested (Fig. 5d). Reference: J Med Microbiol. 2019 Mar;68(3):456-466. https://pubmed.ncbi.nlm.nih.gov/30676310/
In vivo activity: In addition, there was a numerically lower incidence of septic arthritis among mice treated with iclaprim (10–19 % in treated mice compared with 29 % in the infected control) at day 3. Reference: Access Microbiol. 2019 Aug 20;1(7):e000052. https://pubmed.ncbi.nlm.nih.gov/32974543/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 30.0 84.65

Preparing Stock Solutions

The following data is based on the product molecular weight 354.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Bryant AE, Gomi S, Katahira E, Huang DB, Stevens DL. The effects of iclaprim on exotoxin production in methicillin-resistant and vancomycin-intermediate Staphylococcus aureus. J Med Microbiol. 2019 Mar;68(3):456-466. doi: 10.1099/jmm.0.000929. Epub 2019 Jan 24. PMID: 30676310; PMCID: PMC6580997. 2. Schneider P, Hawser S, Islam K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett. 2003 Dec 1;13(23):4217-21. doi: 10.1016/j.bmcl.2003.07.023. PMID: 14623005. 3. Huang DB, Noviello S, Gemmell CG. Iclaprim reduces the incidence and severity of Staphylococcus aureus-induced septic arthritis in a murine model. Access Microbiol. 2019 Aug 20;1(7):e000052. doi: 10.1099/acmi.0.000052. PMID: 32974543; PMCID: PMC7481738.
In vitro protocol: 1. Bryant AE, Gomi S, Katahira E, Huang DB, Stevens DL. The effects of iclaprim on exotoxin production in methicillin-resistant and vancomycin-intermediate Staphylococcus aureus. J Med Microbiol. 2019 Mar;68(3):456-466. doi: 10.1099/jmm.0.000929. Epub 2019 Jan 24. PMID: 30676310; PMCID: PMC6580997. 2. Schneider P, Hawser S, Islam K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett. 2003 Dec 1;13(23):4217-21. doi: 10.1016/j.bmcl.2003.07.023. PMID: 14623005.
In vivo protocol: 1. Huang DB, Noviello S, Gemmell CG. Iclaprim reduces the incidence and severity of Staphylococcus aureus-induced septic arthritis in a murine model. Access Microbiol. 2019 Aug 20;1(7):e000052. doi: 10.1099/acmi.0.000052. PMID: 32974543; PMCID: PMC7481738.

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1: Tahtaoui C, Demailly A, Guidemann C, Joyeux C, Schneider P. Enantioselective synthesis of iclaprim enantiomers--a versatile approach to 2-substituted chiral chromenes. J Org Chem. 2010 Jun 4;75(11):3781-5. doi: 10.1021/jo100566c. PubMed PMID: 20446707.

2: Laue H, Valensise T, Seguin A, Lociuro S, Islam K, Hawser S. In vitro bactericidal activity of iclaprim in human plasma. Antimicrob Agents Chemother. 2009 Oct;53(10):4542-4. doi: 10.1128/AAC.00766-09. Epub 2009 Aug 3. PubMed PMID: 19651909; PubMed Central PMCID: PMC2764211.

3: Oefner C, Parisi S, Schulz H, Lociuro S, Dale GE. 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. Acta Crystallogr D Biol Crystallogr. 2009 Aug;65(Pt 8):751-7. doi: 10.1107/S0907444909013936. Epub 2009 Jul 10. PubMed PMID: 19622858.

4: Entenza JM, Haldimann A, Giddey M, Lociuro S, Hawser S, Moreillon P. Efficacy of iclaprim against wild-type and thymidine kinase-deficient methicillin-resistant Staphylococcus aureus isolates in an in vitro fibrin clot model. Antimicrob Agents Chemother. 2009 Sep;53(9):3635-41. doi: 10.1128/AAC.00325-09. Epub 2009 Jun 29. PubMed PMID: 19564362; PubMed Central PMCID: PMC2737851.

5: Sincak CA, Schmidt JM. Iclaprim, a novel diaminopyrimidine for the treatment of resistant gram-positive infections. Ann Pharmacother. 2009 Jun;43(6):1107-14. doi: 10.1345/aph.1L167. Epub 2009 May 12. Review. PubMed PMID: 19435963.

6: Krievins D, Brandt R, Hawser S, Hadvary P, Islam K. Multicenter, randomized study of the efficacy and safety of intravenous iclaprim in complicated skin and skin structure infections. Antimicrob Agents Chemother. 2009 Jul;53(7):2834-40. doi: 10.1128/AAC.01383-08. Epub 2009 May 4. PubMed PMID: 19414572; PubMed Central PMCID: PMC2704699.

7: Sader HS, Fritsche TR, Jones RN. Potency and bactericidal activity of iclaprim against recent clinical gram-positive isolates. Antimicrob Agents Chemother. 2009 May;53(5):2171-5. doi: 10.1128/AAC.00129-09. Epub 2009 Mar 16. PubMed PMID: 19289528; PubMed Central PMCID: PMC2681558.

8: Morgan A, Cofer C, Stevens DL. Iclaprim: a novel dihydrofolate reductase inhibitor for skin and soft tissue infections. Future Microbiol. 2009 Mar;4(2):131-44. doi: 10.2217/17460913.4.2.131. Review. PubMed PMID: 19257839.

9: Jones RN, Biedenbach DJ, Sader HS. In vitro activity of iclaprim and comparison agents tested against Neisseria gonorrhoeae including medium growth supplement effects. Diagn Microbiol Infect Dis. 2009 Mar;63(3):339-41. doi: 10.1016/j.diagmicrobio.2008.04.002. PubMed PMID: 19216944.

10: Oefner C, Bandera M, Haldimann A, Laue H, Schulz H, Mukhija S, Parisi S, Weiss L, Lociuro S, Dale GE. Increased hydrophobic interactions of iclaprim with Staphylococcus aureus dihydrofolate reductase are responsible for the increase in affinity and antibacterial activity. J Antimicrob Chemother. 2009 Apr;63(4):687-98. doi: 10.1093/jac/dkp024. Epub 2009 Feb 11. PubMed PMID: 19211577.

11: Zhanel GG, Karlowsky JA. In vitro activity of Iclaprim against respiratory and bacteremic isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2009 Apr;53(4):1690-2. doi: 10.1128/AAC.01388-08. Epub 2009 Jan 12. PubMed PMID: 19139284; PubMed Central PMCID: PMC2663069.

12: Morrissey I, Maher K, Hawser S. Activity of iclaprim against clinical isolates of Streptococcus pyogenes and Streptococcus agalactiae. J Antimicrob Chemother. 2009 Feb;63(2):413-4. doi: 10.1093/jac/dkn505. Epub 2008 Dec 4. PubMed PMID: 19059943.

13: Peppard WJ, Schuenke CD. Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic-resistant staphylococcal infections. Curr Opin Investig Drugs. 2008 Feb;9(2):210-25. PubMed PMID: 18246524.

14: Laue H, Weiss L, Bernardi A, Hawser S, Lociuro S, Islam K. In vitro activity of the novel diaminopyrimidine, iclaprim, in combination with folate inhibitors and other antimicrobials with different mechanisms of action. J Antimicrob Chemother. 2007 Dec;60(6):1391-4. Epub 2007 Oct 25. PubMed PMID: 17962215.

15: Laue H, Valensise T, Seguin A, Hawser S, Lociuro S, Islam K. Effect of human plasma on the antimicrobial activity of iclaprim in vitro. J Antimicrob Chemother. 2007 Dec;60(6):1388-90. Epub 2007 Oct 19. PubMed PMID: 17951265.

16: Kohlhoff SA, Sharma R. Iclaprim. Expert Opin Investig Drugs. 2007 Sep;16(9):1441-8. Review. Erratum in: Expert Opin Investig Drugs. 2007 Nov;16(11):1867. PubMed PMID: 17714029.

17: Morrissey I, Hawser S. Activity of iclaprim against Legionella pneumophila. J Antimicrob Chemother. 2007 Oct;60(4):905-6. Epub 2007 Aug 6. PubMed PMID: 17681977.

18: Andrews J, Honeybourne D, Ashby J, Jevons G, Fraise A, Fry P, Warrington S, Hawser S, Wise R. 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. J Antimicrob Chemother. 2007 Sep;60(3):677-80. Epub 2007 Jul 10. PubMed PMID: 17623694.

19: Kohlhoff SA, Roblin PM, Reznik T, Hawser S, Islam K, Hammerschlag MR. In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C. pneumoniae. Antimicrob Agents Chemother. 2004 May;48(5):1885-6. PubMed PMID: 15105151; PubMed Central PMCID: PMC400585.

20: Schneider P, Hawser S, Islam K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett. 2003 Dec 1;13(23):4217-21. PubMed PMID: 14623005.