Selected derivatives of K-252a

Details Selected derivatives of K-252a Selected derivatives of K-252a

1997-06-02

2001-10-23

Scheiner, Laurie (Department: 1648)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S211070, C514S279000

Reexamination Certificate

active

06306849

ABSTRACT:

FIELD OF INVENTION
This invention features selected ring-substituted derivatives of K-252a and their use for treatment of neurological disorders.
BACKGROUND OF THE INVENTION
K-252a is a compound having an indolocarbazole skeleton represented by the following formula [Japanese Published Unexamined Patent Application No. 41489/85 (U.S. Pat. No. 4,555,402)].
It has been reported that K-252a strongly inhibits protein kinase C (PKC) which plays a central role in regulating cell functions, and has various activities such as the action of inhibiting smooth muscle contraction (Jpn. J. Pharmacol. 43(suppl.): 284, 1987), the action of inhibiting serotonin secretion (Biochem. Biophys. Res. Commun., 144: 35, 1987), the action of inhibiting elongation of neuraxone (J. Neuroscience, 8: 715, 1988), the action of inhibiting histamine release (Allergy, 43: 100, 1988), the action of inhibiting smooth muscle MLCK (I. Biol. Chem., 263: 6215, 1988), anti-inflammatory action (Acta Physiol. Hung., 80: 423, 1992), the activity of cell survival (J. Neurochemistry, 64: 1502, 1995), etc. It has also been disclosed in Experimental Cell Research, 193: 175-182, 1991 that K-252a has the activity of inhibiting IL-2 production. Also the complete synthesis of K-252a has been achieved (J. Am. Chem. Soc., 117: 10413, 1995).
On the other hand, it has been disclosed that derivatives of K-252a have PKC inhibitory activity, the activity of inhibiting histamine release (Japanese Published Unexamined Patent Application No. 295588/88), antitumor activity [Japanese Published Unexamined Patent Application No. 168689/89 (U.S. Pat. No. 4,877,776), WO 88/07045 (U.S. Pat. No. 4,923,986)] etc., the action of increasing blood platelets [WO94/06799 (EP 630898A)], vasodepressor activity (Japanese Published Unexamined Patent Application No. 120388/87), the action of accelerating cholinergic neuron functions [WO 94/02488 (U.S. Pat. No. 5,461,146)], curative effect on prostate cancer [WO 94/27982 (U.S. Pat. No. 5,516,771)], etc.
SUMMARY OF THE INVENTION
The present invention relates to selected derivatives of K-252a represented by the general formula:
Constituent members are disclosed in detail, infra. Preferred methods for preparing these compounds and methods for using them are also disclosed.
DETAILED DESCRIPTION


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