公开(公告)号：US09914719B2

公开(公告)日：2018-03-13

申请号：US14467946

申请日：2014-08-25

Applicant: Astex Therapeutics Ltd.

Inventor： Gianni Chessari ,  Miles Stuart Congreve ,  Martyn Frederickson ,  Christopher William Murray ,  Eva Figueroa Navarro ,  Alison Jo-Anne Woolford ,  Maria Grazia Carr ,  Robert Downham ,  Michael Alistair O'Brien ,  Theresa Rachel Phillips ,  Andrew James Woodhead

IPC: A61K31/454 ,  A61K31/496 ,  A61K31/445 ,  A61K31/4035 ,  C07D401/12 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10 ,  C07C65/21

CPC classification number: C07D401/12 ,  C07C65/21 ,  C07D209/08 ,  C07D209/44 ,  C07D215/08 ,  C07D217/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D471/04 ,  C07D471/10 ,  C07D491/08 ,  C07D491/10

Abstract: The invention provides compounds of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group —(O)n—R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The compounds have activity as Hsp90 inhibitors.

公开(公告)号：US09428439B2

公开(公告)日：2016-08-30

申请号：US14149450

申请日：2014-01-07

Applicant: Astex Therapeutics Ltd.

Inventor： Martyn Frederickson ,  John Francis Lyons ,  Neil Thomas Thompson ,  Mladen Vinkovic ,  Brian John Williams ,  Andrew James Woodhead ,  Alison Jo-Anne Woolford

IPC: C07D209/44 ,  C07C67/317 ,  C07C67/313 ,  C07C59/08 ,  C07C69/92 ,  C07C235/60

CPC classification number: C07C67/317 ,  C07C59/08 ,  C07C67/313 ,  C07C69/92 ,  C07C235/60 ,  C07D209/44

Abstract: The invention provides an acid addition salt of a compound of the formula (1). Also provided by the invention are processes for preparing the compound of formula (1) and alkyl analogs thereof, novel intermediates for use in the process and methods for preparing the intermediates. The invention also provides new medical uses of compounds of the formula (1) and its ethyl analog.

Abstract translation: 本发明提供式（1）化合物的酸加成盐。 本发明还提供制备式（1）化合物及其烷基类似物的方法，用于该方法的新中间体和制备中间体的方法。 本发明还提供式（1）化合物及其乙基类似物的新的医学用途。

公开(公告)号：US09051278B2

公开(公告)日：2015-06-09

申请号：US14281360

申请日：2014-05-19

Applicant: Astex Therapeutics, Ltd.

Inventor： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Adrian Liam Gill ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Graham Wyatt

IPC: A61K31/4439 ,  C07D401/12 ,  C07D231/38 ,  A61K31/4152 ,  A61K31/416 ,  A61K31/454 ,  C04B35/632 ,  C07D231/14 ,  C07D231/40 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06

CPC classification number: C07D231/38 ,  A61K31/415 ,  A61K31/4152 ,  A61K31/4155 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06 ,  C04B35/632 ,  C07D231/14 ,  C07D231/40 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04

Abstract: The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0): X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

Abstract translation: 本发明提供式（O）的化合物或其盐或互变异构体或N-氧化物或溶剂合物，用于预防或治疗疾病状态和病症，例如由细胞周期蛋白依赖性激酶和糖原合酶激酶-3介导的癌症。 在式（0）中：X为基团R 1 -A-NR 4 - 或5或6元碳环或杂环; A是键，SO 2，C = O，NR g（C = O）或O（C = O），其中R g是氢或任选被羟基或C 1-4烷氧基取代的C 1-4烃基; Y是长度为1,2或3个碳原子的键或亚烷基链; R1是氢; 具有3至12个环成员的碳环或杂环基; 或任选被一个或多个选自卤素（例如氟），羟基，C 1-4烃氧基，氨基，单或二-C 1-4烃基氨基的取代基取代的C 1-8烃基，以及具有3至 12个环成员，并且其中烃基的1或2个碳原子可以任选地被选自O，S，NH，SO，SO 2的原子或基团取代; R2是氢; 卤素; C 1-4烷氧基（如甲氧基）; 或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基; R 3选自具有3至12个环成员的氢和碳环和杂环基; 和R 4是氢或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基。