Patent ID: 6228850
Filing Date: 2001-05-08
Classification: A61K,C07J,Y10S

Abstract:
A method of preventing, treating or inhibiting tumor associated angiogenesis in a patient, said method comprising administering an effective amount of betulinic acid derivative or a combination of betulinic acid and a betulinic acid derivative to a patient in need thereof, wherein the betulinic acid derivative is of the formula ##STR3##wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 independently or in combination represent the following groups:R is H;R.sub.1 is H, Br, Cl, F or I;when R.sub.2 is H, R.sub.3 is OH, OCOCH.sub.3, OCO(CH.sub.2).sub.n CH.sub.3 (where n=1 to 5),OCOC(CH.sub.3).sub.3,OCO(CH.sub.2).sub.n Cl (where n=1 to 10), OCOC.sub.6 H.sub.5, NH.sub.2,NHCH.sub.2 CH.sub.2 OCOCH.sub.3, OSO.sub.2 CH.sub.3, N.dbd.CHC.sub.6 H.sub.4 Br, N.dbd.CHC.sub.6 H.sub.4 Cl,N.dbd.CHC.sub.6 H.sub.4 NO.sub.2,NHCH.sub.2 CH.sub.2 OCH.sub.3, N.dbd.CHC.sub.6 H.sub.3 (CH.sub.3)CF.sub.3, N.dbd.CHC.sub.6 H.sub.4 CF.sub.3,N.dbd.CHC.sub.6 H.sub.3 Br.sub.2, N.dbd.CHC.sub.6 H.sub.3 Cl.sub.2,N.dbd.CHC.sub.6 H.sub.4 F, OCOC.sub.6 H.sub.4 Br, OCOC.sub.6 H.sub.4 Cl, OCOC.sub.6 H.sub.4 F,N.dbd.CHC.sub.6 H.sub.3 F.sub.2, OCOC.sub.6 H.sub.4 I, OCOC.sub.6 H.sub.3 Cl.sub.2, OCOC.sub.6 H.sub.3 F.sub.2,OCOC.sub.6 H.sub.2 Cl.sub.3, OCOCH(OCOCH.sub.3)CH.sub.3, OCOCH(OCOCH.sub.3)C.sub.6 H.sub.5,OCOCH.sub.2 C.sub.6 H.sub.5 or ##STR4##orR.sub.2 and R.sub.3 together are O, NNHC.sub.6 H.sub.5, HC.sub.6 H.sub.2 Cl.sub.3, NNHC.sub.6 H.sub.4 OCH.sub.3, NNHC.sub.6 H.sub.4 Br, NNHCH.sub.3 Cl.sub.2, NNHC.sub.6 H.sub.3 F.sub.2, NNHC.sub.6 H.sub.4 CF.sub.3, NNC.sub.6 H.sub.3 (CF.sub.3).sub.2, NNHC.sub.6 H.sub.4 OH, NNHC.sub.6 H.sub.3 (Br)(OCH.sub.3); N--OX (where X is H, COCH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or SO.sub.2 C.sub.6 H.sub.4 CH.sub.3), NNHCH.sub.2 C.sub.6 H.sub.5, NNHCH(OH)C.sub.6 H.sub.5, or NNHC.sub.6 H.sub.4 F;when R.sub.2 and R.sub.3 together is O, this represents a carbonyl group;R.sub.4 is O(CH.sub.2).sub.n COOCH.sub.3, O(CH.sub.2).sub.n COOC.sub.2 H.sub.5, O(CH.sub.2).sub.n COOH,O(CH.sub.2).sub.n COCl (where n=1 to 5), OCH.sub.2 CH.sub.2 OC.sub.2 H.sub.5, OCH.sub.2 CH.sub.2 OH,OCH.sub.2 CH.sub.2 OCOCH.sub.3, Cl, N.sub.3, NHNH.sub.2, HNNHC.sub.6 H.sub.4 OMe, orNHNHC.sub.6 H.sub.2 Cl.sub.3 ;R is H or Br;R is CH.sub.3, CH.sub.2 Br, CH.sub.2 OH, CHO, CH.sub.2 OCOCH.sub.3, COOH,COO(CH.sub.2).sub.n COOCH.sub.3,COO(CH.sub.2).sub.n COOC.sub.2 H.sub.5, COO(CH.sub.2).sub.n COOH (where n=1 to 5); orR.sub.5 and R.sub.6 together are X.dbd.CH.sub.2, or >CH --CH.sub.3.