Arterolan
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| Surname | Arterolan | |||||||||
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[ N - (2-Amino-2-methylpropyl) -2- cis -dispiro (adamantane-2,3 '- [1,2,4] trioxolane-5', 1 '' - cyclohexane) -4 '' - yl ] acetamide |
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| Molecular formula | C 22 H 36 N 2 O 4 | |||||||||
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| Molar mass | 392.53 g mol −1 | |||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||
Arterolan is a chemical compound from the group of ozonides and adamantanes .
It is a potential antimalarial agent developed by Medicines for Malaria Venture (MMV) and tested by Ranbaxy Laboratories . From a chemical as well as a pharmacological point of view, Arterolan has some special features, for example it contains a 1,2,4-trioxolane ring (ozonide) and an adamantane system attached to it. In combination with the bis-quinoline piperaquine, it has already advanced to clinical phase III. It works by inhibiting PfATP6 , a calcium ATPase of the malaria pathogen P. falciparum , which influences calcium transport in the endoplasmic reticulum of the muscles ( sarcoplasm ) .
According to Livemint, MMV decided to discontinue funding for the project after preliminary data presented at a conference in 2006 were not very satisfactory when compared to other drug candidates. At that point, Ranbaxy had spent around $ 16 million. Despite the discontinued support of MMV, Ranbaxy is continuing the development of the drug.
Extraction and presentation
The synthesis of Arterolan is based on the Gries coozonolysis of a mixture of adamantane-2-one- O- methyloxime and 4-carbomethoxycyclohexanone to form cis -adamantane-spiro-3'-8'-methoxycarbonylmethyl-1 ', 2', 4 '-trioxaspiro [4.5] decane. The latter is hydrolyzed to cis -adamantane-2-spiro-3'-8'-carboxymethyl-1 ', 2', 4'-trioxaspiro [4.5] decane, followed by mild amidation with the formation of an ozonide intermediate, which by treatment with 2-methylpropane-1,2-diamine finally gives the target compound.
Individual evidence
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ Hartwig, CL, Lauterwasser, EMW, Mahajan, SS, Hoke, JM, Cooper, RA, Renslo, AR Investigating the Antimalarial Action of 1,2,4-Trioxolanes with Fluorescent Chemical Probes. J.Med.Chem. 2011, 54, 8207-8213.
- ↑ CY Patil, MS Baig, SM Doifode, SS Katare: Fixed dose combination of arterolane and piperaquine: A newer prospect in antimalarial therapy. In: Annals of Medical and Health Sciences Research. 4, 2014, p. 466, doi: 10.4103 / 2141-9248.139270 .
- ↑ Anirudh Gautam, Tausif Ahmed, Pradeep Sharma, Brijesh Varshney, Monika Kothari, Nilanjan Saha, Arjun Roy, Joerg J. Moehrle, Jyoti Paliwal: Pharmacokinetics and Pharmacodynamics of Arterolane Maleate Following Multiple Oral Doses in Adult Patients With Malaria. In: The Journal of Clinical Pharmacology. 51, 2011, p. 1519, doi: 10.1177 / 0091270010385578 .
- ↑ Livemint: Blow to Ranbaxy drug research plans, September 21, 2007 , accessed July 25, 2015.
- ↑ Akshat Rathi: The story behind Ranbaxy's new anti-malarial drug, April 2012 , accessed on July 25, 2015.
- ↑ AO Terent'ev, DA Borisov, VA Vil ', VM Dembitsky: Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products. In: Beilstein J Org Chem. 10, 2014, pp. 34-114, PMID 24454562 PMC 3896255 (free full text).