Patent NZ-514847-A (NZ)
Title: Method and kits for using tetrahydronaphthalene derivatives for treating myocardial infarction or stroke, vascular reactivity, coronary diseases or Raynaud? phenomenon
Inventor: DAY WESLEY WARREN
IPC: A61P35/00
Filed: 2001-10-16
Abstract: The estrogen agonist/antagonist of formula (I) wherein: A is selected from CH2 and NR; B, D and E are independently selected from CH and N; Y is phenyl, optionally substituted with 1-3 substituents independently selected from R4; naphthyl, optionally substituted with 1-3 substituents independently selected from R4; C3-C8 cycloalkyl, optionally substituted with 1-2 substituents independently selected from R4; C3-C8 cycloalkenyl, optionally substituted with 1-2 substituents independently selected from R4; 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;  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 a bicyclic 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 -NR7R8;  or formula (II) 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 a bicyclic amine containing five to twelve carbon atoms, either bridged or fused and optionally substituted with 1-3 substituents independently selected from R4; or Z1 and G in combination may be formula (III) W is -CH2-;  -CH=CH-;  -O-;  -NR2-;  -S(O)n-; formula (IV); -CR2(OH)-; -CONR2-; -NR2CO-; formula (V); or -CºC-; 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)alky);  -CO2H;  -CN; -CONHOR; -SO2NHR; -NH2; C1-C4 alkylamino; C1-C4 dialkylamino; -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 carbocyclic 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 R7and 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, 2or 3; q is 0, 1, 2or 3; or an optical or geometric isomer thereof; or a pharmaceutically acceptable salt, N-oxide, ester, quaternary ammonium salt or prodrug thereof. is useful in preventing myocardial infarction or stroke, maintaining or improving vascular reactivity, treating acute or chronic renal failure, peripheral arterial occlusive disease, coronary artery diseases or Raynaud's phenomenon