817210-65-4Relevant academic research and scientific papers
NOVEL CYCLOPENTANE DERIVATIVES
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Page/Page column 40-41, (2010/12/29)
The invention relates to a compound of formula (I) wherein A1 and R1 to R5 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.
Potent, plasmodium-selective farnesyltransferase inhibitors that arrest the growth of malaria parasites: Structure-activity relationships of ethylenediamine-analogue scaffolds and homology model validation
Fletcher, Steven,Cummings, Christopher G.,Rivas, Kasey,Katt, William P.,Hornéy, Carrie,Buckner, Frederick S.,Chakrabarti, Debopam,Sebti, Sa?d M.,Gelb, Michael H.,Van Voorhis, Wesley C.,Hamilton, Andrew D.
supporting information; experimental part, p. 5176 - 5197 (2009/07/01)
New chemotherapeutics are urgently needed to combat malaria. We previously reported on a novel series of antimalarial, ethylenediamine-based inhibitors of protein farnesyltransferase (PFT). In the current study, we designed and synthesized a series of second generation inhibitors, wherein the core ethylenediamine scaffold was varied in order to examine both the homology model of Plasmodium falciparum PFT (PfPFT) and our predicted inhibitor binding mode. We identified several PfPFT inhibitors (PfPFTIs) that are selective for PfPFT versus the mammalian isoform of the enzyme (up to 136-fold selectivity), that inhibit the malarial enzyme with IC50 values down to 1 nM, and that block the growth of P. falciparum in infected whole cells (erythrocytes) with ED50 values down to 55 nM. The structure-activity data for these second generation, ethylenediamine-inspired PFT inhibitors were rationalized by consideration of the X-ray crystal structure of mammalian PFT and the homology model of the malarial enzyme.
Chiral base route to functionalised cyclopentenyl amines: Formal synthesis of the cyclopentene core of nucleoside Q
Oxenford, Sally J.,O'Brien, Peter,Shipton, Mark R.
, p. 9053 - 9055 (2007/10/03)
A chiral base route to a range of highly functionalised amino cyclopentenes has been developed. The key asymmetric step involved the chiral lithium amide base-mediated rearrangement of a protected trans-4-hydroxy cyclopentene oxide to give an allylic alcohol (88% ee). Subsequent Overman rearrangement gave a protected trans-1,2-aminocyclopentenol whereas Mitsunobu substitution with BocNHNs gave a protected cis-amino cyclopentenol. Both are proven intermediates for natural product synthesis. The protected cis-aminocyclopentenol was transformed in a few steps into a precursor of the cyclopentene core of nucleoside Q, a natural product whose deficiency in animals is related to tumour growth.
Total synthesis of (±)-deoxypenostatin A. Approaches to the syntheses of penostatins A and B
Snider,Liu
, p. 8490 - 8498 (2007/10/03)
A short synthesis of (±)-deoxypenostatin A (28) has been carried out using the convergent coupling of dienal 11, epoxide 13, and methylenetriphenylphosphorane (17) to prepare trienol 19 in only two steps. The key step is the Yb(OTf)3-catalyzed intramolecular Diels-Alder reaction of hydrated trienyl glyoxylate 23, which gives lactone 24 stereoselectively. Elaboration of lactone 24 to enone 27 by an intramolecular Horner-Emmons Wittig reaction and epimerization completes the synthesis of 28. Modest yields of Diels-Alder adducts 45a and 46a could be prepared analogously from MEM ether 44c, but the sensitivity of several of the intermediates precluded the elaboration of 45a to penostatin A (1).
