Patent ID: 6780855
Filing Date: 2004-08-24
Classification: A61P,C07J

Abstract:
A 11&bgr;-Halogen-7&agr;-substituted estratriene of formula I whereinR3 is a hydrogen atom, a hydrocarbon radical with up to 8 carbon atoms, or a radical of partial formula R3â€²â€”C(O)â€”, R3â€² is a hydrogen atom or a hydrocarbon radical with up to 8 carbon atoms or a phenyl radical, R11 is a fluorine or chlorine atom, R17 is a hydrogen atom or a radical of partial formula R17â€²â€”C(O)â€”, R17 is a hydrogen atom or a hydrocarbon radical with up to 8 carbon atoms, R7 is a radical of formula â€”Aâ€”Bâ€”Zâ€”R20, A is a direct bond, a phenylene radical, or a benzylidene radical, whereby the methylene group is bonded to the 7-carbon atom of the base steroid structure, B is a straight-chain or branched-chain alkylene, alkenylene or alkinylene group with 3 to 14 carbon atoms, and Z is â€”NR21â€”, â€”SOx, or â€”NR31, when Z is â€”NR21â€”, R21 is a C1-C3 alkyl group, R20 is a hydrogen atom, a straight-chain or branched-chain alkyl, alkenyl or alkinyl group with up to 10 carbon atoms or one of groupings: â€”Dâ€”CnF2+1, â€”Lâ€”CH&boxH;CFâ€”CpF2p+1, â€”Dâ€”Oâ€”(CH2)q-aryl, â€”Dâ€”Oâ€”(CH2)râ€”CnF2n+1, or R20 and R21 with the nitrogen atom to which they are bonded form a saturated or unsaturated heterocycle with 5 or 6 chain links, which optionally contains one or two additional heteroatoms, selected from nitrogen, oxygen and sulfur, and optionally is substituted, D is a straight-chain or branched-chain alkylene, alkenylene or alkinylene group with up to 8 carbon atoms n is an integer from 1 to 8, L is a straight-chain or branched-chain alkylene, alkenylene or alkinylene group with 2 to 7 carbon atoms, p is an integer from 2 to 7, q is 0, 1, 2 or 3, aryl stands for a phenyl radical, 1- or 2-naphthyl radical or a heteroaryl radical that is optionally substituted in one or two places, r is an integer from 1 to 5, or when Z is â€”SOx x is for 0, 1 or 2, R20 is a straight-chain or branched-chain alkyl, alkenyl or alkinyl group with up to 10 carbon atoms, or one of groupings: â€”Dâ€”CnF2+1, â€”Lâ€”CH&boxH;CFâ€”CpF2p+1, â€”Dâ€”Oâ€”(CH2)q-aryl, â€”Dâ€”Oâ€”(CH2)râ€”CnF2n+1, D is a straight-chain or branched-chain alkylene, alkenylene or alkinylene group with up to 8 carbon atoms n is an integer from 1 to 8, L is a straight-chain or branched-chain alkylene, alkenylene or alkinylene group with 2 to 7 carbon atoms, p is an integer from 2 to 7, q is 0, 1, 2 or 3, aryl stands for a phenyl radical, 1- or 2-naphthyl radical or a heteroaryl radical optionally substituted in one or two places, and r stands for an integer from 1 to 5, when Z is â€”NR31, R20 is a straight-chain or branched-chain alkyl, alkenyl or alkinyl radical with up to 14 carbon atoms, which can be interrupted and/or partially fluorinated by one to three heteroatoms â€”Oâ€” and â€”Sâ€” and groupings â€”NR32â€”, R32 is a hydrogen atom or a C1-C3 alkyl radical, an aryl or heteroaryl radical that is optionally substituted in one or two places, a C3-C10 cycloalkyl radical that is optionally substituted in one or two places, a C4-C15 cycloalkylalkyl radical that is optionally substituted in one or two places, a C7-C20 aralkyl radical that is optionally substituted in one or two places, a heteroaryl-C1-C6 alkyl radical that is optionally substituted in one or two places or an optionally substituted aminoalkyl radical, R31 is a radical of formula â€”C(O)R33 or â€”CH2â€”R33, and R33 is a straight-chain or branched-chain, alkyl, alkenyl or alkinyl radical with up to 14 carbon atoms, which can be interrupted and/or partially fluorinated by.one to three heteroatoms â€”Oâ€” and â€”Sâ€” and groupings â€”NR32â€”, in which R32 is a hydrogen atom or a C1-C3 alkyl radical, an aryl or heteroaryl radical that is optionally substituted in one or two places, a C3-C10 cycloalkyl radical that is optionally substituted in one or two places, a C4-C15 cycloalkylalkyl radical that is optionally substituted in one or two places, a C7-C20 aralkyl radical that is optionally substituted in one or two places, a heteroaryl-C1-C6 alkyl radical that is optionally substituted in one or two places, an optionally substituted aminoalkyl radical or a biphenylene radical, excluding the compounds:11&bgr;-fluoro-7&agr;-{5-[N-methyl-N-3-(4,4,5,5,5-pentafluoropentylthio)-propylamino]-pentyl}-estra-1,3,5(10)-triene-3,17&bgr;-diol 11&bgr;-fluoro-7&agr;-{5-[2-(4,4,5,5,5-pentafluoropentylthiomethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-triene-3,17&bgr;-diol 11&bgr;-fluoro-7&agr;-{6-[N-methyl-N-3-(4,4,5,5,5-pentafluoropentylthio)-propylamino]-hexyl}-estra-1,3,5(10)-triene-3,17&bgr;-diol 11&bgr;-fluoro-7&agr;-{5-[(2S)-2-(4-trifluoromethylphenylthiomethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-triene-3,17&bgr;-diol 11&bgr;-fluoro-7&agr;-{5-[(2S)-2-(4,4,5,5,5-pentafluoropentylthiomethyl)-pyrrolidin-1-yl]-pentyl)-estra-1,3,5(10)-triene-3,170-diol 11&bgr;-fluoro-7&agr;-{5-[(2S)-2-(4,4,5,5,5-pentafluoropentanesulfinylmethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-triene-3,17&bgr;-diol 11&bgr;-fluoro-7&agr;-{5-[(2S)-2-(4,4,5,5,5-pentafluoropentanesulfonylmethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-triene-3,17&bgr;-diol.