144328-54-1Relevant articles and documents
Synthesis and complement inhibitory activity of B/C/D-Ring analogues of the fungal metabolite 6,7-diformyl-3′,4′,4a′,5′,6′,7′,8 ′,8a′-octahydro-4,6′,7′-trihydroxy-2′, 5′,5′,8a′-tetramethylspiro[1′(2′H)- naphthalene-2(3H)-benzofuran]
Bradbury, Barton J.,Bartyzel, Piotr,Kaufman, Teodoro S.,Nieto, Marcelo J.,Sindelar, Robert D.,Scesney, Susanne M.,Gaumond, Bruce R.,Marsh Jr., Henry C.
, p. 2697 - 2705 (2007/10/03)
This paper reports the synthesis and the bioassay of 4-methoxy- and 4-hydroxyspiro[benzofuran2(3H)-cyclohexane] partial analogues (5) of the complement inhibitory sesquiterpene fungal metabolite 6,7-diformyl-3′,4′,4a′,5′,6′,7′, 8′,8a′-octahydro-4,6′,7′-trihydroxy-2′, 5′,5′,8a′-tetramethylspiro[1′(2′H)- naphthalene-2 (3H)-benzofuran] (1a, K-76) and its silver oxide oxidized product (lb, K-76COOH). The described target compounds represent spirobenzofuran B/C/D-ring analogues lacking the A-ring component of the prototype structure. The target compounds were evaluated by the inhibition of total hemolytic complement activity in human serum. It was observed that the structurally simplified analogue 4-methoxyspiro[benzofuran-2(3H)cyclohexane]-6-carboxylic acid (5a) exhibited an IC50 = 0.53 mM similar to the IC50 = 0.57 mM that was observed for the natural product derivative 1b. Exhibiting an IC50 = 0.16 mM, the three-ringed partial structure 6-carboxy-7-formyl-4-methoxyspiro[benzofuran-2(3H)-cyclohexane] (5k)was found to be the most potent target compound. Like the natural product, 5k appears to inhibit primarily at the C5 activation step and inhibits both the classical and alternative human complement pathways. Several other analogues inhibited complement activation in vitro at concentrations similar to those required for inhibition by the natural product 1b.
Compounds which inhibit complement and/or suppress immune activity
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, (2008/06/13)
The present invention is directed to compounds which suppress immune responses and/or selectively inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the phamaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activites, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.
Compounds which inhibit complement and/or suppress immune activity
-
, (2008/06/13)
The present invention is directed to compounds which suppress immune responses and/or selectively inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the pharmaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activities, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.
