Novel analogues

Other examples of spirocyclic 2-amino-4(5//)-oxazolones have been prepared and evaluated for their CNS activity and as potential antiviral agents. " In these reports, cyclization of the appropriate ot-hydroxy ester with guanidine afforded the novel analogues 93, albeit in low-to-modest yields. Representative examples are shown in Table 6.4 (Fig. 6.10). 

Very early studies by other workers19-22,88 described the higher potency of arteether relative to artemisinin (1). This had forecast the selective reduction of the lactone of our novel analogues as a routine method, with the likely potential to increase antimalarial activity. Previous transformations of artemisinin are summarized in Scheme 10. 

Anand R, Somasundaram S, Doble M, Paramasivan C (2011) Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA mutants of Mycobacterium tuberculosis. BMC Struct Biol 11 47... 

Claus RA, Wtistholz A, Muller S, Bockmeyer CL, Riedel NH, Kinscherf R, Deigner HP. Synthesis and antiapoptotic activity of a novel analogue of the neutral sphingomyelinase inhibitor scyphostatin. ChemBioChem 2005 6 726-737. 

In a systematic search for novel analogues of the anti-inflammatory indole-3-acetic acid derivative indomethacin (216), scientists at the Pierrel Laboratories in Milan reasoned that substitution of an azido group for the 4-chloro substituent on the A-benzoyl ring might represent an effective bioisosteric replacement, and thus confer interesting biological properties to the molecule [266]. l-(4-Azidobenzoyl)-5-methoxy-2-methyl-l/f-indole-3-acetic acid (zidometacin) (217) was synthesized and evaluated for its... 

Figure 28-21 Themoleculei-thyroxine. 7. binds to prealbumin, a protein found in blood. Based on x-ray data of the >-thyroxine-prealbumin complex, the binding affinity of novel analogues was prediaed by using a molecular modeling approach.

The completion of the total synthesis of 7,ll-e/ /-thyrsiferol (140), a novel analogue of the thyrsiferol family of compounds, prompted us to investigate its potential anticancer properties. To examine the pharmacological profile of 140, we selected sea urchin embryos as a biological system for the in vitro evaluation of antimitotic activity [76]. 

Nucleoside Pyrophosphates. - 2.2.1 Nucleoside Diphosphate Analogues. The enzymatic regeneration of 3 -phosphoadenosine-5 -phosphosulfate (76) catalysed by the rat liver sulfotransferase IV enzyme has been reported to provide useful quantities of the cofactor for enzyme kinetic experiments. The first thio-nucleotide analogues of adenosine 5 -phosphosulfate (77a) and of 3 -phosphoadenosine 5 -phosphosulfate (77b) have been synthesised in enantio-merically pure forms. Using these novel analogues, the sulfuryl transfer reaction to adenosine 5 -triphosphate was shown to proceed with inversion of configuration at the a-phosphorus. ... 

A novel class of non-isopolar but isosteric analogues of diadenosine polyphosphates (124) has been prepared from A, A, 0, 0 -tetrabenzoylade-nosine 3 -0-(2-thiono-l,3,2-oxathiaphospholane) and from tetrabenzoyladenosine. Treatment of the appropriate polyol with 7V, A, 0, 0 -tetrabenzoyladenosine 3 -0-(2-thiono-l,3,2-oxathiaphospho-lane) in the presence of DBU yielded (124). Alternatively, phosphorothioyla-tion of the polyol using 2-chloro-l,3,2-oxathiaphospholane followed by sulfurisation yielded an intermediate that was then condensed with A, A, 0, 0 -tetrabenzoyladenosine in the presence of DBU to yield the isosteric Ap A mimics. Only preliminary evaluations of these novel analogues... 

Cottney J, Rankovic Z, Morphy JR (1999) Synthesis of novel analogues of the delta opioid ligand SNC-80 using REM resin. Bioorg Med Chem Lett 9 1323-1328... 

Allen,J.D., van Loevezijn, A., Lakhai, J.M., van der Valk, M., van Tellingen, O., Reid, G., Schellens, J.H., Koomen, G.J. and Schinkel, A.H. (2002) Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Molecular Cancer Therapeutics, 1, 417 -25. 

Lin S, Khanolkar AD, Fan P, Goutopoulos A, Qin C, Papahadjis D, Makriyannis A (1998) Novel analogues of arachidonylethanolamide (anandamide) affinities for the CBl and CB2 cannabinoid receptors and metabolic stability. J Med Chem 41 5353-5361... 

Matsuda reported the synthesis of a series of 5 -modified novel analogues of the clinically useful immunosuppressant bredinin. These analogues, including the 5 -phosphate (16), were prepared via a novel photochemical imidazole ring cleavage reaction as the key step. ... 

Three novel analogues of cyclic-AMP have been reported. The cyclic phos-phinate ester (108) was prepared by using a double Arbuzov-type condensation of bis-trimethylsilyl phosphinite with a dibromo-sugar, which was subsequently treated with SnCh and adenine after appropriate acetylation. ... 

Since Nielsen et al introduced peptide nucleic acids (PNA), this area has received vast attention, and continues to do so. More recently, the main area of interest has been in novel analogues, and many new ones have been reported. The solid phase synthesis of DNA-3 -PNA chimeras have been described, in which the DNA is attached to the amino terminal of the PNA via the 3 -phosphate or thiophosphate. All chimeras were shown to have superior thermal stability towards either DNA or RNA than a DNA oligomer, and the phosphodiester linkage was more stable than the phosphorothioate. Hybridisation studies with PNA and PNA-DNA chimeras demonstrate that there is a sequence effect for the junction between PNA and DNA on duplex stability. A decamer pyrimidine bis-PNA oligomer, separated by a linker, when targeted to complementary dsDNA formed three distinct structures. One structure contained two bis-PNA units, and the other two were believed to be structural isomers. 

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