NOVEL USE OF MIFEPRISTONE AND DERIVATIVES THEREOF AS HEDGEHOG PROTEIN SIGNALLING PATHWAY MODULATORS AND APPLICATIONS OF SAME

摘要

The use of estra-4,9-dien-3-one derivative steroid compounds (including D-homo-steroid analogs) (I) (i.e. mifepristone (Ia) and related compounds) as medicaments for modulating the hedgehog protein signaling pathway, and treating disorders involving tissue dysfunction associated with deregulation of the pathway, is new. The use of steroid or D-homo-steroid compounds of formula (I) or their salts is claimed in the production of medicaments for modulating (i.e. activating or inhibiting) the hedgehog protein signaling pathway and treating disorders involving tissue dysfunction associated with deregulation of the pathway. R1 = 1-18C organic group, containing at least one N, P or Si atom and bonded to the steroid nucleus via C; R2 = 1-8C hydrocarbyl; X = tri- or tetramethylene group (or unsaturated equivalent), completing a 5- or 6-membered, saturated or unsaturated ring, optionally substituted by one or more of Q1 (optionally substituted by one or more groups Q2) and/or Q2; Q1 = alkyl, alkenyl, aryl or aralkyl or up to 12C; Q2 = OH, CHO, COX1, OX2, COOX3, OCOX4, halo, SH, SX5, SOX6 or SO2X7; X1 - X7 = 1-8C alkyl, 2-8C alkenyl, 2-8C alkynyl, 6-15C aryl or 6-15C aralkyl; C = A = oxo (optionally in ketal-blocked form), CH-OH, CH-OY1, 'alkylcarboxylate -C(=H)(=O)-C(=O)-Y2' (sic), C=NOY3 or CH2; Y1 - Y3 = 1-8C alkyl or 7-15C aralkyl; A1 + A2 = additional C-C bond or -O- (epoxide).