Synthetic compounds for treatment of inflammation

#The subject invention pertains to compounds which are useful as anti-inflammatory agents and to compositions containing such compounds as active ingredients. More particularly, the invention concerns novel uses for biologically active bis-heterocyclic compounds, e.g. bis-indoles, and to pharmaceutical compositions containing these compounds. The novel use of the compounds relates to the anti-inflammatory properties of the disclosed bis-heterocyclic compounds. Specifically exemplified herein are the compounds identified as soritin A, HB-238, Bis(3,3′indolyl)methane, HB-236, 2-Bis(3,3′indolyl) acetaldehyde, HB-237, and their salts, analogs and derivatives.

#The prevention and control of inflammation is of prime importance to man, and much research has been devoted to development of compounds having anti-inflammatory properties. Certain methods and chemical compositions have been developed which aid in inhibiting or controlling inflammation, but additional anti-inflammatory methods and compositions are needed.

#Bis-heterocyclic compounds such as bis-indoles have been previously described as having antimicrobial, antitumor or antiviral activity. Specifically, the bis-indole compounds known as topsentins are disclosed in U.S. Pat. No. 4,866,084. Dragmacidin and its related compounds isolated from the marine sponge of the Dragmacidon sp. are disclosed in U.S. Pat. No. 4,970,226. These patents are herein incorporated by reference. These compounds as well as the homocarbonyl topsentins and hamacanthins have also been described as having inhibitory activity against cellular inflammatory responses. See U.S. Pat. Nos. 5,290,777 and 5,464,835 which are also hereby incorporated by reference. The present invention provides compounds having advantageous potent anti-inflammatory activity.

#FIG. 1 shows the dose response for soritin A (HB-238) as measured by percent inhibition of edema in the PMA-induced mouse ear anti-inflammatory assay.

#FIG. 2 shows the dose response for soritin A (HB-238) as measured by percent inhibition of edema in the RTX-induced mouse ear anti-inflammatory assay.

#The subject invention pertains to a novel use as an anti-inflammatory agent of bis-heterocyclic compounds and compositions comprising the bis-heterocyclic compounds. Surprisingly, the bis-heterocycle compounds of the subject invention can be highly effective in inhibiting immunogenic and neurogenic inflammation.

#In one example, compounds useful according to the subject invention have the following formula:

#R1-10 are the same or different selected from —H, —OH, halogen, —COOH, —COOR, C1-C8 alkyl , C1-C8 alkoxyl, mesyl, tosyl, —OCOR, or NZ1Z2 (wherein the Zs can be the same or different);