Patent NZ-514821-A (NZ)
Title: Methods for assessing, improving, or maintaining urogenital health in postmenopausal women
Inventor: DAY WESLEY WARREN
IPC: A61K31/40
Filed: 2001-10-15
Abstract: An estrogen agonist/antagonist is used for the preparation of a medicament for improving or maintaining urogenital health, lowering vaginal pH, treating an urinary tract infection, treating vaginal dryness, treating vaginal itching, treating undesired vaginal spasms, vaginitis, a vaginal yeast or bacterial infection, vulvar atrophy, urethrocele, cystocele, rectocele, enterocele prolapse, urinary or anal incontinence, undesired urinary frequency or urgency or increasing the frequency of intensity of organisms in a female patient. The agonists is the compound of formula (I) wherein: A is CH2 or NR; B, D and E are CH or N; Y is phenyl, optionally substituted; naphthyl, optionally substituted; C3-C8 cycloalkyl, optionally substituted; C3-C8 cycloalkenyl, optionally substituted; a five membered heterocycle containing up to two heteroatoms selected from the group consisting of -O-, -NR2- and -S(O)n-, optionally substituted; a six membered heterocycle containing up to two heteroatoms selected from the group consisting of -O-, -NR2- and -S(O)n- optionally substituted; 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; Z1 is -(CH2)pW(CH2)q-; -O(CH2)pCR5R6; -O(CH2)pW(CH2)q-; -OCHR2CHR3-; or -SCHR2CHR3; G is -NR7R8; formula (a) wherein 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; or a bicyclic amine containing five to twelve carbon atoms, either bridged or fused and optionally substituted with 1-3 substituents; or Z1and G in combination formula (b); W is -CH2-; -CH=CH-; -O-; -NR2-; -S(O)n-; -C(O)-; -CR2(OH)-; -CONR2-; -NR2CO-; formula (c); -C=C-; R is hydrogen or C1-C6 alkyl; R2 and R3 are hydrogen; or C1-C4 alkyl; R5 and R6 are independently C1-C8 alkyl or together form a C3-C10 carbocyclic ring; R7 and R8 are 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; 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; or an optical or geometric isomer thereof; or a pharmaceutically acceptable salt, N-oxide, ester, quaternary ammonium salt or prodrug thereof. Or is selected from tamoxifen, 4-hydroxy tamoxifen, raloxifene, droloxifene, toremifene, centchroman, idoxifene, 6-(4-hydroxy-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-ol, {4-[2-(2-aza-bicyclo[2.2.1]hept-2-yl)-ethoxy]-phenyl}-[6-hydroxy-2-(4-hydroxy-phenyl)benzo[b]thiophen-3-yl]-methanone, GW 5638, GW 7604, and optical or geometric isomers thereof; and pharmaceutically acceptable salts, N-oxides, esters, quaternary ammonium salts, and prodrugs thereof; or the compounds of formulas V, VI, TSE-424 of formula Va, EM-652 of formula III and EM-800 of formula IV. Provided that when the agonist/antagonist is raloxifene the medicament is not for vulvar atrophy and the when the condition to be treated is urinary incontinence the medicament is not for co-administration with a nitric oxide synthase substrate.