公开(公告)号：US06531497B1

公开(公告)日：2003-03-11

申请号：US09720070

申请日：2001-04-19

申请人： Kyriacos Costa Nicolaou ,  Nigel Paul King ,  Maruice Raymond Verschoyle Finlay ,  Yun He ,  Frank Roschangar ,  Dionisios Vourloumis ,  Hans Vallberg ,  Antony Bigot

发明人： Kyriacos Costa Nicolaou ,  Nigel Paul King ,  Maruice Raymond Verschoyle Finlay ,  Yun He ,  Frank Roschangar ,  Dionisios Vourloumis ,  Hans Vallberg ,  Antony Bigot

IPC分类号： A61K31425

CPC分类号： C07D313/00 ,  C07D417/06 ,  C07D493/04 ,  Y02P20/55

摘要： The invention relates to epothilone analog represented by formula (I) wherein (i) R2 is absent or oxygen; “a” can be either a single or double bond; “b” can be either absent or a single bond; and “c” can be either absent or a single bond, with the proviso that if R2 is oxygen then “b” and “c” are both a single bond and “a” is a single bond; if R2 is absent then “b” and “c” are absent and “a” is a double bond; and if “a” is a double bond, then R2, “b” and “c” are absent; R3 is a radical selected from the group consisting of hydrogen; lower alkyl; —CH═CH2; —C≡CH; —CH2F; —CH2Cl; —CH2—OH; —CH2—O—(C1-C6-alkyl); and —CH2—S—(C1-C6-alkyl); R4 and R5 are independently selected from hydrogen, methyl or a protecting group; and R1 is as defined in the specification, or a salt of a compound of formula (I) where a salt-forming group is present. A further aspect of the invention is related to the synthesis of epothilone E. These compounds have inter alia microtubuli depolymerization inhibiting activity and are e.g. useful against proliferative diseases

摘要翻译： 本发明涉及由式（I）表示的埃坡霉素类似物，其中（i）R2不存在或氧; “a”可以是单键或双键; “b”可以是缺席或单一债券; 和“c”可以不存在或单键，条件是如果R2是氧，则“b”和“c”都是单键，“a”是单键; 如果R2不存在，则“b”和“c”不存在，“a”是双键; 如果“a”是双键，那么R2，“b”和“c”不存在; R3是选自氢的基团; 低级烷基 -CH = CH 2; -C = CH -CH2F; -CH2Cl; -CH 2 -OH; -CH 2 -O-（C 1 -C 6 - 烷基）; 和-CH 2 -S-（C 1 -C 6 - 烷基）; R 4和R 5独立地选自氢，甲基或保护基; 和R1如说明书中所定义，或其中存在成盐基团的式（I）化合物的盐。 本发明的另一方面涉及埃坡霉素E的合成。这些化合物尤其具有微管解聚抑制活性，例如。 对增殖性疾病有用