Disclosed is a method of treating osteoarthritis. The method comprises administering a therapeutic amount of debromohymenialdisine to an individual or animal with osteoarthritis. Debromohymenialdisine is able to slow the joint deterioration and cartilage degradation associated with the disease.
The present invention provides Wondonin A of general formula (I), which is extracted from a two-sponge association of phylum Porifera (sponge) and has antiangiogenic activity, and a process for preparing the same. Wondonin A has no cytotoxicity, but has an inhibitory activity against angiogenesis which is one of the crucial mechanisms of cancer cell metastasis, thus, it can be applied not only as an anticancer drug but also as a therapeutic agent of angiogenesis-associated diseases such as cardiac ischemia, rheumatoid arthritis, and diabetes mellitus. ##STR1##
A method for making debromohymenialdisine (DBH) 2 and analogs thereof is described. One embodiment of the present method first comprises forming hymenin 4, and then converting hymenin into DBH 2 as described herein. One such embodiment first comprises providing a compound having Formula 3 ##STR1## where R is independently selected from the group consisting of hydrogen and lower aliphatic, and X is independently selected from the group consisting of hydrogen and halogen. A compound having Formula 3, such as Compound 10 with R and X as hydrogen, is then converted to DBH 2 or an analog thereof. An alternative embodiment of the method comprises forming Compound 30 or Compound 32, which are then directly converted to DBH 2. Alternatively, Compound 30 can be converted to Compound 10, which is then subsequently converted to DBH 2 by reaction with a halogen in the presence of an acid. The method of the present invention can be used to make analogs of DBH 2, including alkoxy derivatives, such as Compound 12, and conjugated diene derivatives, such as Compound 14.
Disclosed is a method of treating an individual or animal with osteoarthritis. The method comprises administering to the individual or animal a therapeutically effective amount of a protein tyrosine kinase inhibitor.
The synthesis and biological activity of indoloazepines and acid amine salts thereof which are structurally related to naturally-occurring hymenialdisine is disclosed. Naturally-occurring hymenialdisine obtained from the sponge is a potent inhibitor of production of cytokines interleukin-2 (IL-2) and tumor necrosis factor-.alpha. (TNF-.alpha.). The chemically-synthesized indoloazepines of the invention also inhibit production of IL-2 and TNF-.alpha.. The indoloazepines are useful for treating inflammatory diseases, particularly diseases associated with kinases NF-.kappa.B or GSK-3.beta. activation or NF-.kappa.B activated gene expression products. The indoloazepines are useful for the treatment of cancer by the inhibition of kinases CHK1 and CHK2.
The synthesis and biological activity of indoloazepines and acid amine salts thereof which are structurally related to naturally-occurring hymenialdisine is disclosed. Naturally-occurring hymenialdisine obtained from the sponge is a potent inhibitor of production of cytokines interleukin-2 (IL-2) and tumor necrosis factor-.alpha. (TNF-.alpha.). The chemically-synthesized indoloazepines of the invention also inhibit production of IL-2 and TNF-.alpha.. The indoloazepines are useful for treating inflammatory diseases, particularly diseases associated with kinases NF-.kappa.B or GSK-3.beta. activation or NF-.kappa.B activated gene expression products. The indoloazepines are useful for the treatment of cancer by the inhibition of kinases CHK1 and CHK2.
