Arterolane

{{Short description|Chemical compound}}

{{Drugbox

| verifiedrevid = 451552022

| IUPAC_name = [(N-(2-amino-2-methylpropyl)-2-cis-dispiro(adamantane-2,3'-[1,2,4]trioxolane-5',1"-cyclohexan)-4"-yl]acetamide

| image = Arterolane.svg

| tradename =

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| legal_US =

| legal_status =

| routes_of_administration = Oral

| bioavailability =

| protein_bound =

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| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 664338-39-0

| ATC_prefix = P01

| ATC_suffix = BX02

| ATC_supplemental = (combination with piperaquine)

| PubChem = 10475633

| ChEBI = 136054

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 25069705

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 3N1TN351VB

| C=22 | H=36 | N=2 | O=4

| 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

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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-

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = VXYZBLXGCYNIHP-SSPKTAKCSA-N

}}

Arterolane, also known as OZ277 or RBx 11160, is an antimalarial compound marketed by Ranbaxy Laboratories.{{cite web | vauthors = Unnikrishnan CH | url = http://www.livemint.com/2007/09/21011423/Blow-to-Ranbaxy-drugresearch.html | archive-url = https://web.archive.org/web/20070925033703/https://www.livemint.com/2007/09/21011423/blow-to-ranbaxy-drugresearch.html | archive-date = 25 September 2007 | title = Blow to Ranbaxy drug research plans | work = LiveMint.com | date = 21 September 2007 }} It was discovered by US and European scientists coordinated by the Medicines for Malaria Venture (MMV).{{cite journal | vauthors = Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN | display-authors = 6 | title = Identification of an antimalarial synthetic trioxolane drug development candidate | journal = Nature | volume = 430 | issue = 7002 | pages = 900–4 | date = August 2004 | pmid = 15318224 | doi = 10.1038/nature02779 | bibcode = 2004Natur.430..900V | s2cid = 4320974 }} Its molecular structure is uncommon for pharmacological compounds in that it has both an ozonide (trioxolane) group and an adamantane substituent.{{cite journal |display-authors=6 |vauthors=Dong Y, Wittlin S, Sriraghavan K, Chollet J, Charman SA, Charman WN, Scheurer C, Urwyler H, Santo Tomas J, Snyder C, Creek DJ, Morizzi J, Koltun M, Matile H, Wang X, Padmanilayam M, Tang Y, Dorn A, Brun R, Vennerstrom JL |date=January 2010 |title=The structure-activity relationship of the antimalarial ozonide arterolane (OZ277) |journal=Journal of Medicinal Chemistry |volume=53 |issue=1 |pages=481–91 |doi=10.1021/jm901473s |pmid=19924861}}{{cite web | url = https://www.science.org/content/blog-post/ozonides-drugs-what-will-they-think-next | work = In the Pipeline | title = Ozonides As Drugs: What Will They Think Of Next? | first = Derek | last = Lowe | name-list-style = vanc | date = 23 November 2009 | access-date = 17 November 2015 | publisher = Sciencemag.org }}

Initial results were disappointing, and in 2007 MMV withdrew support, after having invested $20M in the research; Ranbaxy said at the time that it intended to continue developing arterolane in combination with another drug. In 2009, Ranbaxy started a Phase II clinical trial of arterolane in combination with piperaquine, and it was published in 2015.{{cite web | title = 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 | work = India Clinical trials registry | url = http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=734 }}{{cite journal | vauthors = Toure OA, Rulisa S, Anvikar AR, Rao BS, Mishra P, Jalali RK, Arora S, Roy A, Saha N, Iyer SS, Sharma P, Valecha N | display-authors = 6 | title = 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 | journal = Malaria Journal | volume = 14 | pages = 469 | date = November 2015 | pmid = 26608469 | pmc = 4660726 | doi = 10.1186/s12936-015-0982-y | doi-access = free }}

In 2012, Ranbaxy obtained approval to market an arterolane/piperaquine combination drug in India, under the brand name Synriam.{{cite web | first = Akshat | last = Rathi | name-list-style = vanc | work = Chemistry World | date = 3 May 2012 | url = http://www.rsc.org/chemistryworld/2012/05/ranbaxy-launches-new-anti-malarial-synriam | title = Ranbaxy launches new anti-malarial Synriam }} In 2014, the product was also approved in Nigeria, Uganda, Senegal, Cameroon, Guinea, Kenya and Ivory Coast.{{cite news | author = Staff | work = Business Standard | date = 16 December 2014 | url = http://www.business-standard.com/content/b2b-pharma/ranbaxy-receives-approval-for-malaria-drug-synriam-from-7-african-countries-114121700050_1.html | title = Ranbaxy receives approval for malaria drug Synriam from 7 African countries }}