Patent IL-120267-A (IL)
Title: Use of estrogen antagonists and estrogen agonists in the preparation of a medicament for treating pathological conditions
IPC: A61K31/445
Filed: 1997-02-20
Abstract: The use of an effective amount of a compound, as defined below in the preparation of a medicament for treating or preventing pathological conditions which are susceptible or partially susceptible to inhibition by an estrogen, antiestrogen or estrogen agonist, selected from the group consisting of Alzheimer's disease, premenstrual syndrome, peri-menopausal syndrome, a deficiency of thrombomodulin, uterine fibrosis, excessive myeloperoxidase activity, excessive thrombin, autoimmune disease, reperfusion damage of ischemic myocardium and insufficient testosterone; said compound being of the formula wherein: A is selected from CH2 and NR; B, D and E are independently selected from CH and N; Y is (a) phenyl, optionally substituted with 1-3 3135 ה' בכסלו התשס" ג - November 10, 2002 substituents independently selected from R4; (b) naphthyl, optionally substituted with 1-3 substituents independently selected from R4; (c) C3-C8 cycloalkyl, optionally substituted with 1-2 substituents independently selected from R4; (d) C3-C8 cycloalkenyl, optionally substituted with 1-2 substituents independently selected from R4; (e) a five membered heterocycle containing up to two heteroatoms selected from the group consisting of -O-, -NR2- and -S(O)n-, optionally substituted with 1-3 substituents independently selected from R4; (f) a six membered heterocycle containing up to two heteroatoms selected from the group consisting of -O-, -NR2- and -S(O)n- optionally substituted with 1-3 substituents independently selected from R4; or (g) a bicylic ring system consisting of a five or six membered heterocyclic ring fused to a phenyl ring, said heterocyclic ring containing up to two heteroatoms selected from the group consisting of -O-, -NR2-, and -S(O)n-, optionally substituted with 1-3 substituents independently selected from R4; Z1 is -(CH2)p W(CH2)q-; -O(CH2)pCR5R6-; -O(CH2)pW(CH2)q; -OCHR2CHR3-; or -SCHR2CHR3-; G is (a) -NR7R8; (b) wherein n is 0, 1 or 2; m is 1, 2 or 3; Z2 is -NH-, -O-, -S-, or -CH2-; optionally fused on adjacent carbon atoms with one or two phenyl rings and, optionally independently substituted on carbon with one to three substituents and, optionally, independently on nitrogen with a chemically suitable substituent selected from R4; or (c) a bicyclic amine containing five to twelve carbon atoms, either bridged or fused and optionally substituted with 1-3 substituents independently selected from R4; Z1 and G in combination may be W is -CH2-;-CH=CH-;-NR2-;-S(O)n-; 3136 ה' בכסלו התשס" ג - November 10, 2002 -CR2(OH)-; -CONR2-; -NR2CO-; -C=C-; R is hydrogen or C1-C6 alkyl; R2 and R3 are independently hydrogen; or C1-C4 alkyl; R4 is hydrogen; halogen; C1-C6 alkyl; C1-C4 alkoxy; C1-C4 acyloxy; C1-C4 alkylthio; C1-C4 alkylsulfinyl; C1-C4 alkylsulfonyl; hydroxy (C1-C4) alkyl; aryl (C1-C4) alkyl; -CO2H; -CN;-CONHOR;-SO2NHR;-NH2; C1-C4 alkylamino; -NHSO2R;-NO2;-aryl; or-OH R5 and R6 are independently C1-C8 alkyl or together form a C3-C10 carbocyclic ring; R7 and R8 are independently phenyl; a C3-C10 carbocylic ring, saturated or unsaturated; a C3-C10 heterocyclic ring containing up to two heteroatoms, selected from -O-, -N- and -S-; H; C1-C6 alkyl; or form a 3 to 8 membered nitrogen containing ring with R5 or R6; R7 and R8 in either linear or ring form may optionally be substituted with up to three substituents independently selected from C1-C6 alkyl, halogen, alkoxy, hydroxy and carboxy; a ring formed by R7 and R8 may be optionally fused to a phenyl ring; e is 0, 1 or 2; m is 1, 2 or 3; n is 0, 1 or 2; p is 0, 1, 2 or 3; q is 0, 1, 2 or 3; and optical and gemoeteric isomers thereof, and non toxic pharmacologically acceptable acid addition salts, N-oxides, esters, and quaternary ammonium salts thereof, substantially as described in the specification. 3137 ה' בכסלו התשס" ג - November 10, 2002