Arterolane

Arterolane, also known as OZ277 or RBx 11160, is a substance that was tested for antimalarial activity[1] by Ranbaxy Laboratories.[2] It was discovered by US and European scientists who were coordinated by the Medicines for Malaria Venture (MMV).[3] Its molecular structure is uncommon for pharmacological compounds in that it has both an ozonide (trioxolane) group and an adamantane substituent.[4]

Arterolane
Clinical data
Routes of
administration		Oral
ATC code
Identifiers
IUPAC name
  • [(N-(2-amino-2-methylpropyl)-2-cis-dispiro(adamantane-2,3'-[1,2,4]trioxolane-5',1"-cyclohexan)-4"-yl]acetamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H36N2O4
Molar mass392.540 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)(N)CN=C(O)C[C@H]1CC[C@]2(CC1)OO[C@]1(O2)[C@H]2C[C@@H]3C[C@H](C2)C[C@H]1C3
InChI
  • InChI=1S/C22H36N2O4/c1-20(2,23)13-24-19(25)12-14-3-5-21(6-4-14)26-22(28-27-21)17-8-15-7-16(10-17)11-18(22)9-15/h14-18H,3-13,23H2,1-2H3,(H,24,25)/t14-,15-,16+,17-,18+,21+,22- Y
  • Key:VXYZBLXGCYNIHP-SSPKTAKCSA-N Y
  (verify)

Initial results were disappointing, and in 2007 MMV withdrew support, after having invested $20M in the research;[5] Ranbaxy said at the time that it intended to continue developing the drug combination on its own.[2] Ranbaxy started a Phase II clinical trial of arterolane, in combination with piperaquine in 2009 that published in 2015.[6][7]

In 2012, Ranbaxy obtained approval to market the arterolane/piperaquine combination drug in India, under the brand name Synriam,[5] and in 2014 received approval to market it in Nigeria, Uganda, Senegal, Cameroon, Guinea, Kenya and Ivory Coast; it had already received approval in Uganda.[8]

References
  1. Dong Y, Wittlin S, Sriraghavan K, Chollet J, Charman SA, Charman WN, et al. (January 2010). "The structure-activity relationship of the antimalarial ozonide arterolane (OZ277)". Journal of Medicinal Chemistry. 53 (1): 481–91. doi:10.1021/jm901473s. PMID 19924861.
  2. Unnikrishnan CH (21 September 2007). "Blow to Ranbaxy drug research plans". LiveMint.com. Archived from the original on 25 September 207.
  3. Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, et al. (August 2004). "Identification of an antimalarial synthetic trioxolane drug development candidate". Nature. 430 (7002): 900–4. Bibcode:2004Natur.430..900V. doi:10.1038/nature02779. PMID 15318224. S2CID 4320974.
  4. Lowe D (23 November 2009). "Ozonides As Drugs: What Will They Think Of Next?". In the Pipeline. Sciencemag.org. Retrieved 17 November 2015.
  5. Rathi A (3 May 2012). "Ranbaxy launches new anti-malarial Synriam". Chemistry World.
  6. "Phase II trial of dispersible fixed dose combination of arterolane (RBx 11160) maleate and piperaquine phosphate in pediatric patients with acute uncomplicated Plasmodium falciparum malaria". India Clinical trials registry.
  7. Toure OA, Rulisa S, Anvikar AR, Rao BS, Mishra P, Jalali RK, et al. (November 2015). "Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study". Malaria Journal. 14: 469. doi:10.1186/s12936-015-0982-y. PMC 4660726. PMID 26608469.
  8. Staff (16 December 2014). "Ranbaxy receives approval for malaria drug Synriam from 7 African countries". Business Standard.


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