Indolocarbazoles. 1. Total synthesis and protein kinase inhibiting characteristics of compounds related to K-252c.

McCombie, Stuart W.; Bishop, Robert W; Carr, Donna; Dobek, E.; Kirkup, Michael P.; Kirschmeier, Paul T.; Lin, Sue‐Ing; Petrin, Joanne; Rosinski, Karen; Shankar, B. B.; Wilson, Oswald

doi:10.1016/s0960-894x(00)80013-x

Cited by 33 publications

(17 citation statements)

References 28 publications

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“…SCH 47112 ( Fig. 1) is a further indolocarbazole derivative, a synthetic analogue of K-252a, that inhibits PKC in vitro at nanomolar concentrations (IC 50 = 1.7 nM, compared with IC 50 of 7 nM for staurosporine) [24,25].…”

Section: Introductionmentioning

confidence: 99%

SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin

Reynolds

McCombie²,

Shankar³

et al. 1997

Archives of Dermatological Research

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Protein kinase C (PKC) regulates keratinocyte growth and differentiation as well as inflammation in skin, processes which are abnormal in skin diseases such as psoriasis. 12-O-tetradecanoylphorbol-13-acetate (TPA) binds to and activates PKC. We investigated the effects of SCH 47112, a novel staurosporine derivative, which interacts with the catalytic domain of PKC, on TPA-induced inflammation and hyperplasia in hairless mouse skin and TPA-induced differentiation in cultured human keratinocytes. Dorsal mouse skin was treated with vehicle, TPA (2.0/ 2.5 nmol) or SCH 47112 followed by TPA. Epidermal thickness, and epidermal, upper dermal and deep dermal inflammation (assessed on an ordinal semiquantitative scale) were determined in biopsies taken 24 h and 48 h post-treatment. SCH 47112 (100 nmol) inhibited TPA-induced epidermal, upper dermal and deep dermal inflammation by 71%, 45% and 22%, respectively, at 24 h (n = 3, P < 0.05). TPA-induced epidermal hyperplasia was inhibited by SCH 47112 (400 nmol) by 38% at 48 h (n = 3, P < 0.05). In addition, in cultured human keratinocytes, SCH 47112 inhibited TPA induction of transglutaminase. I protein, which catalyzes the formation of crosslinked envelopes. These results indicate that SCH 47112 exhibits biological activity, inhibiting TPA-induced changes in hairless mouse skin in vivo and cultured human keratinocytes in vitro, and suggest that PKC inhibitors may have a therapeutic role in inflammatory skin diseases.

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Section: Introductionmentioning

confidence: 99%

SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin

Reynolds

McCombie²,

Shankar³

et al. 1997

Archives of Dermatological Research

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“…[14] The desired isomer of the two glycosylated indolocarbazoles was then deprotected using TFA and thioanisole to provide the target with a longest linear sequence of seven steps.…”

Section: Use Of Donor–acceptor Cyclopropanes As Intermediates In Natumentioning

confidence: 99%

Synthetic Applications and Methodological Developments of Donor−Acceptor Cyclopropanes and Related Compounds

O’Connor

Wood

Stoltz

2016

Israel Journal of Chemistry

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Donor–acceptor cyclopropanes are convenient precursors to reactive and versatile 1,3-dipoles, and have found application in the synthesis of a variety of carbo- and heterocyclic scaffolds. This perspective review details our laboratory’s use of donor–acceptor cyclopropanes as intermediates toward the total synthesis of various natural products. We also discuss our work in the development of novel cycloadditions and rearrangements of donor–acceptor cyclopropanes and aziridines, as well as an example of an aryne insertion proceeding via fragmentation of a transient donor–acceptor cyclobutane.

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“…Bayer, 1995 Winterfield, 1983Moody, 1990Magnus, 1984Prudhomme, 1992 Bergman, 1989 Gribble, 1992Steglich, 1980Weinreb, 1984Bergman, 1987McCombie, 1993 Kaneko/Clardy, 1985…”

Section: Motivation For the Chaptermentioning

confidence: 99%

“…It was not until 1995 that the first total synthesis of staurosporine (1) was reported by Danishefsky et al [40]. A central challenge in total synthesis by previous groups was that of constructing the two glycosidic bonds to weakly nucleophilic indolic nitrogens [41][42][43][44]. Danishefsky observed oxazolidinone glycal 27b to function as the glycosyl donor and bis(indolyl)maleimide 26 to function as the aglycon acceptor (Scheme 3).…”

Section: About This Pathwaymentioning

confidence: 99%

Strategies Towards the Synthesis of Staurosporine Indolocarbazole Alkaloid and Its Analogues

Rao¹,

Oliveira²,

Varala³

2016

Scope of Selective Heterocycles From Organic and Pharmaceutical Perspective

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Indolocarbazoles. 1. Total synthesis and protein kinase inhibiting characteristics of compounds related to K-252c.

Cited by 33 publications

References 28 publications

SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin

SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin

Synthetic Applications and Methodological Developments of Donor−Acceptor Cyclopropanes and Related Compounds

Strategies Towards the Synthesis of Staurosporine Indolocarbazole Alkaloid and Its Analogues

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