Patent Number: 6,251,920

Title: Prevention and treatment of cardiovascular pathologies

Abstract: A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (I): ##STR1## wherein Z is C.dbd.O or a covalent bond; Y is H or O(C.sub.1 -C.sub.4)alkyl, R.sup.1 and R.sup.2 are individually (C.sub.1 -C.sub.4)alkyl or together with N are a saturated heterocyclic group, R.sup.3 is ethyl or chloroethyl, R.sup.4 is H or together with R.sup.3 is --CH.sub.2 --CH.sub.2 -- or --S--, R.sup.5 is I, O(C.sub.1 -C.sub.4)alkyl or H and R.sup.6 is I, O(C.sub.1 -C.sub.4)alkyl or H with the proviso that when R.sup.4, R.sup.5, and R.sup.6 are H, R.sup.3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to activate or stimulate production of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene and salts thereof. Further provided is a method for identifying a compound that is a TGF-beta activator or production stimulator is provided. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifen or structural analogs thereof, including compounds of formula (I).

Inventors: Grainger; David J. (Cambridge, GB), Metcalfe; James C. (Cambridge, GB), Weissberg; Peter L. (Cambridge, GB)

Assignee: NeoRx Corporation

International Classification: A61K 9/00 (20060101); A61K 31/135 (20060101); A61K 31/00 (20060101); A61K 31/138 (20060101); A61K 47/48 (20060101); A61K 31/407 (20060101); A61K 31/40 (20060101); A61K 31/403 (20060101); A61K 31/337 (20060101); A61K 31/4035 (20060101); A61K 31/4025 (20060101); A61K 31/38 (20060101); C07K 14/435 (20060101); C07K 16/18 (20060101); C07K 16/22 (20060101); C07K 14/71 (20060101); A61K 031/445 (); A61K 031/40 (); A61K 031/38 (); A61K 031/135 ()

Expiration Date: 06/26/2018