公开(公告)号：EP1254111A1

公开(公告)日：2002-11-06

申请号：EP01900108.0

申请日：2001-01-10

申请人： Leo Pharma A/S

发明人： HANSEN, Kai, Holst

IPC分类号： C07C401/00 ,  A61K31/59 ,  A61P19/10

CPC分类号： C07C401/00

摘要： Compounds of the formula (I) wherein X represents hydrogen or hydroxy; R?1 and R2¿, which may be the same or different, represent hydrogen, (C¿1?-C4)alkyl optionally substituted with one hydroxyl group or one or more fluorine atoms, or, together with the carbon atom to which they are attached, R?1 and R2¿ form a (C¿3?-C5)carbocyclic ring; R?3¿ represents (C¿1?-C4)alkyl, (C1-C4)alkoxy or a halogen atom, such as fluorine, chlorine, bromine, or iodine, and in-vivo hydrolyzable esters thereof with pharmaceutically acceptable acids, may be used in the prophylaxis and/or treatment of diseases characterized by abnormal cell differentiation and/or cell proliferation.

公开(公告)号：EP1556345B1

公开(公告)日：2010-12-15

申请号：EP03757738.4

申请日：2003-10-23

申请人： LEO PHARMA A/S

发明人： BINDERUP, Ernst, Torndal ,  HANSEN, Kai, Holst ,  BRETTING, Claus, Aage, Svensgaard ,  CALVERLEY, Martin, John

IPC分类号： C07C401/00 ,  A61K31/59 ,  A61P5/20

CPC分类号： C07C401/00 ,  A61K31/59 ,  A61K31/593

摘要： Compounds according to formula I: in which formula R1 and R2, which may be the same or different, represent halogen, (C1-C6) hydrocarbyl, optionally substituted with one or two hydroxyl group on one or more fluorine atoms, or, together with the carbon atom to which they are both attached, R1 and R2 form a (C3-C6)carbocyclic ring, or one of R1 and R2 taken together with R3 forms a direct bond, such that a triple bond is constituted, or R1 and R2 represent both hydrogen; R3 when not forming a direct bond with one of R1 and R2 represents hydrogen or (C1-C3)hydrocarbyl; X represents (E)-ethylene, (Z)-ethylene, ethynylene, or a bond; Y and Z independently represent hydrogen or methyl; the bond between C#16 and C#17 is depicted with a dotted line to illustrate that said bond may be either a single bond, in which case the projection of the ring substituents is beta, or a double bond; A represents hydroxyl, fluorine or hydrogen; B represents CH2 or H2; the configuration is the 3-position corresponds to the same configuration as in natural vitamine D3 (normal), or the configuration in the configuration in the 3-position is opposite to that of natural vitamin D3(epi); with the proviso that when X represents (E)-ethylene or (Z)-ethylene, one of R1 and R2 taken together with R3 may not form a direct bond, such that a triple bond is constituted; with the further proviso that when X represents a bond R1 ands R2 are nor hydrogen; with the further proviso that the compound of formula I is not 3(S)-hyroxy-9, 10-secocholesta-5(Z),7(E),10(19),22(E),24-penta-ene; and prodrugs and stereo isomeric forms thereof are provided together with their use in therapy, and their use in the manufacture of medicaments.

公开(公告)号：EP1556345A1

公开(公告)日：2005-07-27

申请号：EP03757738.4

申请日：2003-10-23

申请人： LEO PHARMA A/S

发明人： BINDERUP, Ernst, Torndal ,  HANSEN, Kai, Holst ,  BRETTING, Claus, Aage, Svensgaard ,  CALVERLEY, Martin, John

IPC分类号： C07C401/00 ,  A61K31/59 ,  A61P5/20

CPC分类号： C07C401/00 ,  A61K31/59 ,  A61K31/593

摘要： Compounds according to formula I: in which formula R1 and R2, which may be the same or different, represent halogen, (C1-C6) hydrocarbyl, optionally substituted with one or two hydroxyl group on one or more fluorine atoms, or, together with the carbon atom to which they are both attached, R1 and R2 form a (C3-C6)carbocyclic ring, or one of R1 and R2 taken together with R3 forms a direct bond, such that a triple bond is constituted, or R1 and R2 represent both hydrogen; R3 when not forming a direct bond with one of R1 and R2 represents hydrogen or (C1-C3)hydrocarbyl; X represents (E)-ethylene, (Z)-ethylene, ethynylene, or a bond; Y and Z independently represent hydrogen or methyl; the bond between C#16 and C#17 is depicted with a dotted line to illustrate that said bond may be either a single bond, in which case the projection of the ring substituents is beta, or a double bond; A represents hydroxyl, fluorine or hydrogen; B represents CH2 or H2; the configuration is the 3-position corresponds to the same configuration as in natural vitamine D3 (normal), or the configuration in the configuration in the 3-position is opposite to that of natural vitamin D3(epi); with the proviso that when X represents (E)-ethylene or (Z)-ethylene, one of R1 and R2 taken together with R3 may not form a direct bond, such that a triple bond is constituted; with the further proviso that when X represents a bond R1 ands R2 are nor hydrogen; with the further proviso that the compound of formula I is not 3(S)-hyroxy-9, 10-secocholesta-5(Z),7(E),10(19),22(E),24-penta-ene; and prodrugs and stereo isomeric forms thereof are provided together with their use in therapy, and their use in the manufacture of medicaments.