Synthetic studies on the furan ring of wortmannin

Norman, Bryan H.; Paschal, Jonathan W.; Vlahos, Chris J.

doi:10.1016/0960-894x(95)00191-u

Cited by 25 publications

(53 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pattern of inhibition of PI3K we obtained was consistent with the observations of Norman. 13, 12 Norman obtained an IC 50 of 80 nM for a Wm reacted at C20 with the secondary amine, diethylamine, compared to an IC 50 of 36.7 nM we obtained for Wm reacted with the secondary amine, 6-(N-methylamino)-hexanoic acid, see Table 3 (2a). Norman obtained an IC 50 of greater than 500 nM for Wm reacted at C20 with the primary amine, ethylamine, which compared well with the IC 50 of greater than 1000 nM we obtained for Wm reacted with the primary amine 6-aminohexanoic acid (2b).…”

Section: Discussionmentioning

confidence: 94%

Wortmannin-C20 Conjugates Generate Wortmannin

et al. 2005

View full text Add to dashboard Cite

We report on C20-6-(N-methylamino)hexanoic conjugates of wortmannin featuring a tertiary enamine attached to the C20 that inhibit phosphoinositol-3-OH kinase (PI3K) by producing wortmannin (Wm) through an intramolecular attack. The generation of Wm by these conjugates permits the design of Wm based PI3K inhibitors that need not fit into the ATP pocket of PI3K, including Wm conjugates of BSA, IgG, or beads. Wm generating WmC20-N(Me)-hexanoate conjugates offer an approach to the design of targeted or slow release forms of Wm which may inhibit PI3K in tissues more selectively than the parent Wm, a compound which has desirable anti-inflammatory and anti-proliferative activities but which also has a variety of toxic effects.

show abstract

Section: Discussionmentioning

confidence: 94%

Wortmannin-C20 Conjugates Generate Wortmannin

et al. 2005

View full text Add to dashboard Cite

show abstract

“…An analogous epimerisation via an oxazole was observed by Griehl et al during their synthesis of Boc-AlaSer-OH using the carbodiimide method. [26] The antiangiogenesis activity of analogues 4 and 5 was evaluated by the rat aortic ring test. [27] The IC 50 values found (20 to 30 nM) are of the same magnitude as those for the cytotoxic effect of these molecules measured in the L1210 cell line.…”

Section: Resultsmentioning

confidence: 99%

“…13 28.18 (C-6), 27.41 (C-4 or C-5), 26.17 (C-3), 22.96 (CH 3 CHCH 3 ), 22.33 (C-5ЈЈ) ppm. MS (ES, Na): m/z ϭ 393.…”

mentioning

confidence: 98%

The Synthesis of Two Furan‐Based Analogues of the α′,β′‐Epoxy Ketone Proteasome Inhibitor Eponemycin

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Highly electrophilic C-21 position of wortmannin was suggested to be responsible for its activity. 12,14 Till today, several wortmannin analogues (Fig. 2) were synthesized to be used as reporters for detection of PI3-kinase, especially two [ 125 I] radiolabeled compounds 2b and 3 were reported as probes that can be used to monitor the reactivity of wortmannin analogues with proteins in SDS–PAGE.…”

Section: Introductionmentioning

confidence: 99%