5579-63-5Relevant academic research and scientific papers
2-(Acyloxy)ethylphosphonate analogues of prenyl pyrophosphates: synthesis and biological characterization
Cermak, Diana M.,Wiemer, David F.,Lewis, Kriste,Hohl, Raymond J.
, p. 2729 - 2737 (2000)
2-(Acyloxy)ethylphosphonate analogues of geranyl, farnesyl, and geranylgeranyl pyrophosphate have been prepared. Horner-Wadsworth-Emmons condensation of different terpene aldehydes with an unsymmetrical bisphosphonate was the key step in syntheses of the phosphonates bearing α,β-unsaturated acyloxy groups. After preparation of the respective phosphonic acids through reaction with TMSBr, both acids and esters were tested for their effects on DNA synthesis in human-derived myeloid and lymphoid leukemia cell lines. The phosphonate esters varied substantially in their ability to impair proliferation of the different cell lines, but testing against one possible target, farnesyl protein transferase (FPTase), revealed little impact at concentrations ranging up to 10μM. Because the corresponding 2,3-dihydro compounds showed similar biological activity, conjugate addition would not appear to be involved in the toxicity. Copyright (C) 2000 Elsevier Science Ltd.
Bishomoisoprenoid triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase
Wills, Veronica S.,Metzger, Joseph I.,Allen, Cheryl,Varney, Michelle L.,Wiemer, David F.,Holstein, Sarah A.
, p. 2437 - 2444 (2017/04/03)
Protein geranylgeranylation reactions are dependent on the availability of geranylgeranyl diphosphate (GGDP), which serves as the isoprenoid donor. Inhibition of GGDP synthase (GGDPS) is of interest from a drug development perspective as GGDPS inhibition results in impaired protein geranylgeranylation, which in multiple myeloma, disrupts monoclonal protein trafficking and induces apoptosis. We have recently reported a series of isoprenoid triazole bisphosphonates and have demonstrated that a 3:1 mixture of homogeranyl and homoneryl isomers potently, and in a synergistic manner, inhibits GGDPS. We now present the synthesis and biological evaluation of a novel series of bishomoisoprenoid triazoles which furthers our understanding of the structure-function relationship of this class. These studies demonstrate the importance of chain length and olefin stereochemistry on inhibitory activity.
Synthesis of phosphatidylinositol 3-kinase (PI3K) inhibitory analogues of the sponge meroterpenoid liphagal
Pereira, Alban R.,Strangman, Wendy K.,Marion, Frederic,Feldberg, Larry,Roll, Deborah,Mallon, Robert,Hollander, Irwin,Andersen, Raymond J.
experimental part, p. 8523 - 8533 (2011/02/26)
Analogues of the sponge meroterpenoid liphagal (1) have been synthesized and evaluated for inhibition of PI3Kα and PI3Kα as part of a program aimed at developing new isoform-selective PI3K inhibitors. One of the analogues, compound 24, with IC50/sub
Squalene-hopene cyclase: Insight into the role of the methyl group on the squalene backbone upon the polycyclization cascade. Enzymatic cyclization products of squalene analogs lacking a 26-methyl group and possessing a methyl group at C(7) or C(11)
Nakano, Shin-Ichi,Ohashi, Shumi,Hoshino, Tsutomu
, p. 2012 - 2022 (2007/10/03)
To provide deep insight into the polycyclization reaction of squalene, some analogs were synthesized and incubated with the cell-free homogenates of the recombinant Escherichia coli encoding the wild-type squalene cyclase. The presence of C(6)-Me leads to an efficient polycyclization cascade. Substitution of the C(14)-H and the C(18)-H with a methyl group halted the polycylization reaction at the tricyclic ring stage having a 6/6/6-fused ring system and the tetracycle with a 6/6/6/6-fused ring, respectively, both of which were produced according to a Markovnikov closure. Replacement of the C(7)-H and the C(11)-H with a methyl group led to no cyclization. These results, in conjunction with our previous reports, indicated that the methyl positions are important for bringing to completion of the normal polycylization reaction and further demonstrated that the precise steric bulk size at the methyl positions of squalene is critical to the correct folding and the strong binding of the substrate to the squalene cyclase.
Asymmetric synthesis of rhopaloic acid a analogues and their biological properties
Nishitani, Hiroko,Sasaoka, Asami,Tokumasu, Munetaka,Ohkata, Katsuo
, p. 35 - 38 (2007/10/03)
Some of rhopaloic acid A analogues were synthesized and their bioactivity was investigated on the basis of the inhibition of gastrulation of sea urchin embryos.
Insect Juvenile Hormone Analogues: Part XI - Synthesis of Some Heteroaromatic Undecenyl and Geranyl Amides and Their Homologues
Vig, O. P.,Trehan, I. R.,Kad, G. L.,Bedi, Asha Lata,Ghose, J.
, p. 1052 - 1055 (2007/10/02)
Synthesis of some heteroaromatic long chain amides and the corresponding amines starting from undecenoic acid, 4,8-dimethyl-3(E),7-nonadienoic acid (III) and 5,9-dimethyl-4(E),8-decadienoic acid (V) and a few heteroaromatic amines are described.The compounds have been tested on common Indian red cotton bug for their JH activity.
