139727-68-7Relevant academic research and scientific papers
Structure-activity relationships of the antimalarial agent artemisinin. 8. Design, synthesis, and CoMFA studies toward the development of artemisinin-based drugs against leishmaniasis and malaria
Avery, Mitchell A.,Muraleedharan, Kannoth M.,Desai, Prashant V.,Bandyopadhyaya, Achintya K.,Furtado, Marise M.,Tekwani, Babu L.
, p. 4244 - 4258 (2007/10/03)
Artemisinin (1) and its analogues have been well studied for their antimalarial activity. Here we present the antimalarial activity of some novel C-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. Further, antileish
ARTEMISININ-BASED PEROXIDE COMPOUNDS AS BROAD SPECTRUM ANTI-INFECTIVE AGENTS
-
Page/Page column 22, (2010/02/07)
Described herein is the synthesis, bioassay results and utility of new C-9 and C-10 substituted artemisinin derivatives with easily functionalizable groups attached to the artemisinin skeleton through carbon chain or heteroatoms. Described also is the demonstration of this class of compounds for their broad-spectrum anti-parasitic activity. Certain of these analogs possess noticeable cytotoxicity deliberately focused on treatment of cancerous diseases.
Structure-activity relationships of the antimalarial agent artemisinin. 7. Direct modification of (+)-artemisinin and in vivo antimalarial screening of new, potential preclinical antimalarial candidates
Avery, Mitchell A.,Alvim-Gaston, Maria,Vroman, Jeffrey A.,Wu, Baogen,Ager, Arba,Peters, Wallace,Robinson, Brian L.,Charman, William
, p. 4321 - 4335 (2007/10/03)
On the basis of earlier reported quantitative structure-activity relationship studies, a series of 9β-16-(arylalkyl)-10-deoxoartemisinins were proposed for synthesis. Several of the new compounds 7 and 10-14 were synthesized employing the key synthetic intermediate 23. In a second approach, the natural product (+)-artemisinic acid was utilized as an acceptor for conjugate addition, and the resultant homologated acids were subjected to singlet oxygenation and acid treatment to provide artemisinin analogues. Under a new approach, we developed a one step reaction for the interconversion of artemisinin 1 into artemisitene 22 that did not employ selenium-based reagents and found that 2-arylethyliodides would undergo facile radical-induced conjugate addition to the exomethylene lactone of 22 in good yield. The lactone carbonyls were removed sequentially by diisobutylaluminum hydride reduction followed directly by a second reduction (BF3-etherate/Et3SiH) to afford the desired corresponding pyrans. Six additional halogen-substituted aromatic side chains were installed via 22 furnishing the bioassay candidates 15-20. The analogues were examined for in vitro antimalarial activity in the W-2 and D-6 clones of Plasmodium falciparum and were additionally tested in vivo in Plasmodium berghei- and/or Plasmodium yoelii-infected mice. Several of the compounds emerged as highly potent orally active candidates without obvious toxicity. Of these, two were chosen for pharmacokinetic evaluation, 14 and 17.
Copper(I) catalyzed conjugate addition of Grignard reagents to acrylic acids: Homologation of artemisinic acid and subsequent conversion to 9-substituted artemisinin analogs
Vroman, Jeffrey A.,Khan, Ikhlas A.,Avery, Mitchell A.
, p. 6173 - 6176 (2007/10/03)
A new route to novel 9-substituted-10-deoxoartemisinin analogs (13, 14) was developed employing photoxygenation of homologated derivatives of artemisinic acid (9, 10). Conjugate addition to the acrylate moiety of artemisinic acid 2 was made possible by in situ protection as a silyl ester, Cu(I)-catalyzed 1,4-addition of RMgX, and deprotection.
Structure-Activity Relationships of the Antimalarial Agent Artemisinin. 1. Synthesis and Comparative Molecular Field Analysis of C-9 Analogs of Artemisinin and 10-Deoxoartemisinin
Avery, Mitchell A.,Gao, Fenglan,Chong, Wesley K. M.,Mehrotra, Sanjiv,Milhous, Wilbur K.
, p. 4264 - 4275 (2007/10/02)
A series of C-9 β-substituted artemisinin analogs (2-21) were synthesized via dianion alkylation of the total synthetic intermediate 57 followed by subsequent ozonolysis/acidification, or by alkylation of the enolate derived from (+)-9-desmethylartemisini
