公开(公告)号：WO2008047138A3

公开(公告)日：2009-02-19

申请号：PCT/GB2007004000

申请日：2007-10-19

Applicant: UNIV LONDON ,  BARTS & LONDON NHS TRUST ,  JOEL SIMON PETER ,  MARSON CHARLES MICHAEL

Inventor： JOEL SIMON PETER ,  MARSON CHARLES MICHAEL

IPC: C07D285/08

CPC classification number: C07D285/08 ,  C07C233/07 ,  C07C259/06

Abstract: The present invention provides histone deacetylase inhibitors of general formula (I), a process for the preparation of such compounds and uses of the compounds in medicine, especially in the treatment of cancers: in which R1 is an optionally substituted aryl, arylalkyl, heteroaryl, heterocycloalkenyl, cycloalkene ring, cycloalkyl, heterocycloalkyl or a combination of such rings to form a linked or fused ring system, R2 and R3 is each independently hydrogen, optionally substituted saturated or unsaturated alkyl, optionally substituted aryl or heteroaryl, or a combination thereof to form a linked or fused ring system, alkoxy, thioalkoxy, hydroxyl, hydroxyalkyl, halo, haloalkyl, cyano, nitro, amino, amido, alkylamino, alkylcarbonyloxy, alkoxycarbonyl, alkylcarbonyl, alkylthiocarbonyl, alkylsulfonylamino, aminosulfonyl, alkylsulfinyl, or alkylsulfonyl, or R3 is absent when Y stands for O or S, or R2 and R3 may be linked together and such that, together with the intervening atoms, they form a 5, 6 or 7-membered ring containing one or more heteroatoms, which may be a heteroaryl ring, heterocycloalkenyl ring, or heterocycloalkyl ring, optionally containing up to 4 heteroatoms, e.g. oxygen, nitrogen or sulphur, which ring may be fused to further rings as part of a fused ring system, and which may bear 1, 2 or 3 substituents, which substituents independently have the same meaning as R2 on any or all of those rings, Q stands for an (alkyl, which may be unsaturated; aryl, arylalkyl, alkylaryl or alkylarylalkyl, all of which may be optionally substituted; and may be optionally interrupted by O, S, NR, CO, C(N=R), where R may be independently hydrogen, alkyl, alkenyl, alkynyl, or alkoxy; V is OH, SH, SR, OR, NH2, NHR, NRR, NROH, NHOR, NROR where R may independently be hydrogen or (C1-C6) alkyl, Y is oxygen, or sulphur or N, and Z is O, S, S(=O), S(O)2, NR4, -N=, CR4R5, or -C(R4)=, where R4 and R5 independently have the same meaning as R2.

Abstract translation: 本发明提供通式（I）的组蛋白脱乙酰酶抑制剂，这种化合物的制备方法及其用途，特别是在治疗癌症中：其中R 1为任选取代的芳基，芳烷基，杂芳基， 杂环烯基，环烯烃环，环烷基，杂环烷基或这些环的组合以形成连接或稠合的环体系，R 2和R 3各自独立地为氢，任选取代的饱和或不饱和的烷基，任选取代的芳基或杂芳基，或其组合形成 连接或稠合的环系，烷氧基，硫代烷氧基，羟基，羟基烷基，卤素，卤代烷基，氰基，硝基，氨基，酰氨基，烷基氨基，烷基羰基氧基，烷氧基羰基，烷基羰基，烷硫基羰基，烷基磺酰基氨基，氨基磺酰基，烷基亚磺酰基或烷基磺酰基，或R3不存在 当Y代表O或S时，或者R 2和R 3可以连接在一起，使得它们与中间原子一起形成 含有一个或多个杂原子的5,6或7元环，其可以是杂芳基环，杂环烯基环或杂环烷基环，任选地含有至多4个杂原子，例如。 氧，氮或硫，该环可以作为稠环体系的一部分与另外的环稠合，并且其可以带有1,2或3个取代基，这些取代基独立地具有与任何或所有这些环上的R 2相同的含义， Q代表（烷基，其可以是不饱和的;芳基，芳基烷基，烷基芳基或烷基芳基烷基，它们都可以任选地被取代;并且可以任选地被O，S，NR，CO，C（N = R）间隔，其中 R可以独立地是氢，烷基，烯基，炔基或烷氧基; V是OH，SH，SR，OR，NH 2，NHR，NRR，NROH，NHOR，NROR，其中R可以独立地是氢或（C1-C6）烷基， Y是氧或硫或N，Z是O，S，S（= O），S（O）2，NR4，-N =，CR4R5或-C（R4）=，其中R4和R5独立地具有 与R2相同的含义。

公开(公告)号：WO2008047138A2

公开(公告)日：2008-04-24

申请号：PCT/GB2007/004000

申请日：2007-10-19

Applicant: UNIVERSITY COLLEGE LONDON ,  BARTS AND THE LONDON NHS TRUST ,  JOEL, Simon, Peter ,  MARSON, Charles, Michael

Inventor： JOEL, Simon, Peter ,  MARSON, Charles, Michael

CPC classification number: C07D285/08 ,  C07C233/07 ,  C07C259/06

Abstract: The present invention provides histone deacetylase inhibitors of general formula (I), a process for the preparation of such compounds and uses of the compounds in medicine, especially in the treatment of cancers: in which R 1 is an optionally substituted aryl, arylalkyl, heteroaryl, heterocycloalkenyl, cycloalkene ring, cycloalkyl, heterocycloalkyl or a combination of such rings to form a linked or fused ring system, R 2 and R 3 is each independently hydrogen, optionally substituted saturated or unsaturated alkyl, optionally substituted aryl or heteroaryl, or a combination thereof to form a linked or fused ring system, alkoxy, thioalkoxy, hydroxyl, hydroxyalkyl, halo, haloalkyl, cyano, nitro, amino, amido, alkylamino, alkylcarbonyloxy, alkoxycarbonyl, alkylcarbonyl, alkylthiocarbonyl, alkylsulfonylamino, aminosulfonyl, alkylsulfinyl, or alkylsulfonyl, or R 3 is absent when Y stands for O or S, or R 2 and R 3 may be linked together and such that, together with the intervening atoms, they form a 5, 6 or 7-membered ring containing one or more heteroatoms, which may be a heteroaryl ring, heterocycloalkenyl ring, or heterocycloalkyl ring, optionally containing up to 4 heteroatoms, e.g. oxygen, nitrogen or sulphur, which ring may be fused to further rings as part of a fused ring system, and which may bear 1, 2 or 3 substituents, which substituents independently have the same meaning as R 2 on any or all of those rings, Q stands for an (alkyl, which may be unsaturated; aryl, arylalkyl, alkylaryl or alkylarylalkyl, all of which may be optionally substituted; and may be optionally interrupted by O, S, NR, CO, C(N=R), where R may be independently hydrogen, alkyl, alkenyl, alkynyl, or alkoxy; V is OH, SH, SR, OR, NH2, NHR, NRR, NROH, NHOR, NROR where R may independently be hydrogen or (C 1 -C 6 ) alkyl, Y is oxygen, or sulphur or N, and Z is O, S, S(=O), S(O)2, NR 4 , -N=, CR 4 R 5 , or -C(R4)=, where R 4 and R 5 independently have the same meaning as R 2 .

Abstract translation: 本发明提供了通式（I）的组蛋白脱乙酰酶抑制剂，这种化合物的制备方法和该药物在药物中的用途，特别是在治疗癌症中的用途：其中R 1是 任选取代的芳基，芳基烷基，杂芳基，杂环烯基，环烯烃环，环烷基，杂环烷基或这些环的组合以形成连接或稠合的环体系，R 2和R 3， 各自独立地为氢，任选取代的饱和或不饱和烷基，任选取代的芳基或杂芳基，或其组合以形成连接或稠合的环体系，烷氧基，硫代烷氧基，羟基，羟基烷基，卤素，卤代烷基，氰基，硝基，氨基，酰氨基 当Y代表O或S或R 2时，不存在烷基氨基，烷基羰基氧基，烷氧基羰基，烷基羰基，烷硫基羰基，烷基磺酰基氨基，氨基磺酰基，烷基亚磺酰基或烷基磺酰基或R 3， 和R 3可以连接至 并且使得它们与插入的原子一起形成含有一个或多个杂原子的5,6或7元环，杂原子可以是杂芳基环，杂环烯基环或杂环烷基环，任选地含有至多4个杂原子，例如。 氧，氮或硫，该环可以作为稠环系统的一部分与另外的环稠合，并且其可以带有1,2或3个取代基，该取代基独立地具有与R 2相同的含义， 在任何或所有这些环上，Q表示（烷基，其可以是不饱和的;芳基，芳基烷基，烷基芳基或烷基芳基烷基，其全部可以被任选取代;并且可以任选地被O，S，NR，CO， C（N = R），其中R可以独立地是氢，烷基，烯基，炔基或烷氧基; V是OH，SH，SR，OR，NH 2，NHR，NRR，NROH，NHOR，NROR，其中R可以独立地是氢 或（C 1 -C 6）烷基，Y是氧或硫或N，并且Z是O，S，S（= O），S（O） 2，NR 4，-N =，CR 4 R 5或-C（R 4）=，其中R 4， / SUP>和R 5独立地具有与R 2相同的含义。