公开(公告)号：US20140163042A1

公开(公告)日：2014-06-12

申请号：US14179880

申请日：2014-02-13

申请人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Charles Moffat ,  Kenneth William John Baker ,  Alastair David Graham Donald

发明人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Charles Moffat ,  Kenneth William John Baker ,  Alastair David Graham Donald

IPC分类号： C07D471/04 ,  C07C237/40 ,  C07D333/70 ,  C07C317/50 ,  C07D295/192 ,  C07D217/26

CPC分类号： C07C237/40 ,  C07C259/06 ,  C07C275/24 ,  C07C311/46 ,  C07C317/50 ,  C07C2601/08 ,  C07C2601/14 ,  C07D207/416 ,  C07D209/42 ,  C07D213/40 ,  C07D217/02 ,  C07D217/22 ,  C07D217/26 ,  C07D295/185 ,  C07D295/192 ,  C07D333/70 ,  C07D471/04

摘要： Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(═O), —S(═O)2—, —C(═O)O—, —C(O)NR3—, —C(═S)—NR3, —C(═NH)NR3 or —S(═O)2NR3— wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X2-Q1- or -Q1-X2— wherein X2 is —O—, S— or NRA— wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, Alk1 and Alk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NRA—) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl; X1 represents a bond; —C(═O); or —S(═O)2—; —NR4C(═O)—, —C(═O)NR4—, —NR4C(═O)NR5—, —NR4S(═O)2—, or —S(═O)2NR4— wherein R4 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R1R2NH—Y-L1-X1-[CH2]Z— and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONIIOII, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.

公开(公告)号：US20130116318A1

公开(公告)日：2013-05-09

申请号：US12957829

申请日：2010-12-01

申请人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

发明人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

IPC分类号： A61K31/381 ,  A61K31/27

CPC分类号： C07C237/40 ,  C07C259/06 ,  C07C275/24 ,  C07C311/46 ,  C07C317/50 ,  C07C2601/08 ,  C07C2601/14 ,  C07D207/416 ,  C07D209/42 ,  C07D213/40 ,  C07D217/02 ,  C07D217/22 ,  C07D217/26 ,  C07D295/185 ,  C07D295/192 ,  C07D333/70 ,  C07D471/04

摘要： Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers:

摘要翻译： 式（I）化合物是组蛋白脱乙酰酶活性的抑制剂，可用于治疗例如癌症：

公开(公告)号：US07939666B2

公开(公告)日：2011-05-10

申请号：US11918139

申请日：2006-05-04

申请人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

发明人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

IPC分类号： C07D471/02 ,  C07D217/00 ,  C07D213/72 ,  C07D209/04 ,  C07D333/50 ,  C07C229/28

CPC分类号： C07C237/40 ,  C07C259/06 ,  C07C275/24 ,  C07C311/46 ,  C07C317/50 ,  C07C2601/08 ,  C07C2601/14 ,  C07D207/416 ,  C07D209/42 ,  C07D213/40 ,  C07D217/02 ,  C07D217/22 ,  C07D217/26 ,  C07D295/185 ,  C07D295/192 ,  C07D333/70 ,  C07D471/04

摘要： Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers.

摘要翻译： 式（I）化合物是组蛋白脱乙酰酶活性的抑制剂，可用于治疗例如癌症。

公开(公告)号：US08686032B2

公开(公告)日：2014-04-01

申请号：US12957829

申请日：2010-12-01

申请人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

发明人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

IPC分类号： A61K31/381 ,  A61K31/27 ,  C07C271/02 ,  C07C271/06

CPC分类号： C07C237/40 ,  C07C259/06 ,  C07C275/24 ,  C07C311/46 ,  C07C317/50 ,  C07C2601/08 ,  C07C2601/14 ,  C07D207/416 ,  C07D209/42 ,  C07D213/40 ,  C07D217/02 ,  C07D217/22 ,  C07D217/26 ,  C07D295/185 ,  C07D295/192 ,  C07D333/70 ,  C07D471/04

摘要： Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers:

摘要翻译： 式（I）化合物是组蛋白脱乙酰酶活性的抑制剂，可用于治疗例如癌症：

公开(公告)号：US20090291978A1

公开(公告)日：2009-11-26

申请号：US11918139

申请日：2006-05-04

申请人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

发明人： Alan Hornsby Davidson ,  Sanjay Ratilal Patel ,  Francesca Ann Mazzei ,  Stephen John Davies ,  Alan Hastings Drummond ,  David Festus Moffat ,  Kenneth William John Baker ,  Alistair David Graham Donald

IPC分类号： A61K31/437 ,  C07D471/02 ,  C07C229/28 ,  A61K31/216 ,  A61K31/192 ,  C07D217/00 ,  A61K31/472 ,  C07D213/72 ,  A61K31/44 ,  C07D209/04 ,  A61K31/404 ,  C07D333/50 ,  A61K31/381 ,  A61P35/00 ,  A61P25/00 ,  A61P29/00 ,  A61P3/10 ,  A61P37/06

CPC分类号： C07C237/40 ,  C07C259/06 ,  C07C275/24 ,  C07C311/46 ,  C07C317/50 ,  C07C2601/08 ,  C07C2601/14 ,  C07D207/416 ,  C07D209/42 ,  C07D213/40 ,  C07D217/02 ,  C07D217/22 ,  C07D217/26 ,  C07D295/185 ,  C07D295/192 ,  C07D333/70 ,  C07D471/04

摘要： Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, C(═O)—, —S(═O)2—, —C(—O)O—, —C(O)NR3—, —C(═S)—NR3, —C(═NH)NR3 or —S(═O)2NR3— wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L is a divalent radical of formula -(Alk1)m(O)n(Alk2)p— wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X2-Q1- or -Q1-X2— wherein X2 is —O—, S— or NRA— wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or hetero-cyclic radical having 5-13 ring members, AIk1 and AIk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NRA-) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl; X represents a bond; —C(═O); or —S(═O)2—; —NR4C(═O)—, —C(═O)NR4—, —NR4C(═O)NR5—, —NR4S(═O)2—, or —S(═O)2NR4— wherein R4 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R1R2NH—Y-L1-X1—[CH2]z— and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONHOH, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.

公开(公告)号：US20100216802A1

公开(公告)日：2010-08-26

申请号：US12446008

申请日：2007-10-19

申请人： David Festus Charles Moffat ,  Sanjay Ratilal Patel ,  Stephen John Davies ,  Kenneth William John Baker ,  Oliver James Philps

发明人： David Festus Charles Moffat ,  Sanjay Ratilal Patel ,  Stephen John Davies ,  Kenneth William John Baker ,  Oliver James Philps

IPC分类号： A61K31/519 ,  C07D475/00 ,  A61P35/00

CPC分类号： C07D475/00

摘要： Compound of formula (I) are inhibitors of Polo-like kinases (PLKs), and are useful in treatment of cell proliferative diseases: wherein R1 and R2 are hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R3 and R3′ are independently selected from hydrogen, —CN, hydroxyl, halogen, optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl, —NR5R6 or C1-C4 alkoxy, wherein R5 and R6 are independently hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or a ring system having up to 12 ring atoms; T is a radical of formula R-L1-Y1— wherein R is an alpha amino acid or alpha amino acid ester motif, linked to ring A by linker R-L1-Y1— as defined in the claims.

摘要翻译： 式（I）化合物是Polo样激酶（PLK）的抑制剂，可用于治疗细胞增殖性疾病：其中R 1和R 2为氢，或任选取代的（C 1 -C 6）烷基，（C 2 -C 6） 烯基，（C 2 -C 6）炔基或（C 3 -C 6）环烷基; R3和R3'独立地选自氢，-CN，羟基，卤素，任选取代的（C1-C6）烷基，（C2-C6）烯基，（C2-C6）炔基或（C3-C6）环烷基，-NR5R6或 C 1 -C 4烷氧基，其中R 5和R 6独立地是氢或任选取代的（C 1 -C 6）烷基; 环A是任选取代的具有至多12个环原子的单环或双环碳环或杂环或环系; T是式R-L1-Y1-的基团，其中R是通过如权利要求中所定义的连接体R-L1-Y1-连接到环A的α氨基酸或α氨基酸酯基序。

公开(公告)号：US20110190306A1

公开(公告)日：2011-08-04

申请号：US12989178

申请日：2009-04-23

申请人： David Festus Charles Moffat ,  Sanjay Ratilal Patel ,  Kenneth William John Baker ,  Carl Leslie North

发明人： David Festus Charles Moffat ,  Sanjay Ratilal Patel ,  Kenneth William John Baker ,  Carl Leslie North

IPC分类号： A61K31/519 ,  C07D475/00 ,  A61P35/00

CPC分类号： C07D475/00

摘要： Compounds of formula (I) are PLK inhibitors, useful for the treatment of cell proliferative diseases: wherein R1 is hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R2 is hydrogen, or an optionally substituted (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl group; R3 is hydrogen, —CN, hydroxyl, halogen, optionally substituted (C1C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl or (C3-C6)cycloalkyl, —NR5R6 or C1-C4 alkoxy, wherein R5 and R6 are independently hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or a ring system having up to 12 ring atoms; T is a radical of formula R-L1-Y1— wherein L1 and Y1 are as defined in the claims and R is an carbon-linked, alpha alpha disubstituted amino acid or amino acid ester residue.

摘要翻译： 式（I）化合物是可用于治疗细胞增殖性疾病的PLK抑制剂：其中R 1是氢或任选取代的（C 1 -C 6）烷基，（C 2 -C 6）烯基，（C 2 -C 6）炔基或（ C3-C6）环烷基; R 2是氢或任选取代的（C 1 -C 6）烷基，（C 2 -C 6）烯基，（C 2 -C 6）炔基或（C 3 -C 6）环烷基; R 3是氢，-CN，羟基，卤素，任选取代的（C 1 -C 6）烷基，（C 2 -C 6）烯基，（C 2 -C 6）炔基或（C 3 -C 6）环烷基，-NR 5 R 6或C 1 -C 4烷氧基， R6独立地为氢或任选取代的（C 1 -C 6）烷基; 环A是任选取代的具有至多12个环原子的单环或双环碳环或杂环或环系; T是式R-L1-Y1-的基团，其中L1和Y1如权利要求中所定义，R是碳连接的α-α取代的氨基酸或氨基酸酯残基。