公开(公告)号：US20190231887A1

公开(公告)日：2019-08-01

申请号：US16255947

申请日：2019-01-24

Applicant: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

Inventor： Alan Hornsby DAVIDSON ,  Alan Hastings DRUMMOND ,  Lindsey Ann NEEDHAM

IPC: A61K47/54 ,  C07D277/46 ,  C07D471/04 ,  C07C237/22 ,  C07D215/233 ,  C07D213/73

CPC classification number: A61K47/542 ,  A61K47/54 ,  C07C237/22 ,  C07C2601/08 ,  C07D213/73 ,  C07D215/233 ,  C07D277/46 ,  C07D471/04

Abstract: Covalent conjugation of an alpha amino acid ester to a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid, leads to accumulation of the carboxylic acid hydrolysis product in the cell and enables improved or more prolonged enzyme or receptor modulation relative to the unconjugated modulator.

公开(公告)号：US20210361772A1

公开(公告)日：2021-11-25

申请号：US17326470

申请日：2021-05-21

Applicant: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

Inventor： Alan Hornsby DAVIDSON ,  Alan Hastings DRUMMOND ,  Lindsey Ann NEEDHAM

IPC: A61K47/54 ,  C07C237/22 ,  C07D213/73 ,  C07D215/233 ,  C07D277/46 ,  C07D471/04

Abstract: Covalent conjugation of an alpha amino acid ester to a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid, leads to accumulation of the carboxylic acid hydrolysis product in the cell and enables improved or more prolonged enzyme or receptor modulation relative to the unconjugated modulator.

公开(公告)号：US20160137594A1

公开(公告)日：2016-05-19

申请号：US15004039

申请日：2016-01-22

Applicant: GlaxoSmithKline Intellectual Property Development Limited

Inventor： Alan Hornsby DAVIDSON ,  David Festus Charles MOFFAT ,  Francesca Ann DAY ,  Alastair David Graham DONALD

IPC: C07C259/06 ,  C07D241/04 ,  C07D211/58 ,  C07D211/34 ,  C07C311/19 ,  C07D213/56

CPC classification number: C07C259/06 ,  C07C311/19 ,  C07C2601/08 ,  C07C2601/14 ,  C07D211/34 ,  C07D211/58 ,  C07D213/56 ,  C07D215/22 ,  C07D241/04 ,  C07D333/70 ,  C07D409/12 ,  C07D471/04

Abstract: Compounds of formula (I) inhibit HDAC activity: wherein A, B and D independently represent ═C— or ═N—; W is a divalent radical —CH═CH— or CH2CH2—; R1 is an ester group; R2 is the side chain of a natural or non-natural alpha-amino acid; z is 0 or 1; and Y, L1, and X1 are as defined in the claims.

Abstract translation: 式（I）的化合物抑制HDAC活性：其中A，B和D独立地表示= C-或= N-; W是二价基团-CH = CH-或CH 2 CH 2 - ; R1是酯基; R2是天然或非天然α-氨基酸的侧链; z为0或1; Y，L1和X1如权利要求中所定义。

公开(公告)号：US20140323531A1

公开(公告)日：2014-10-30

申请号：US14324510

申请日：2014-07-07

Applicant: GlaxoSmithKline Intellectual Property Development Limited

Inventor： Alan Hornsby DAVIDSON ,  David Festus Charles Moffat ,  Francesca Ann Day ,  Alastair David Graham Donald

IPC: C07D213/56

CPC classification number: C07C259/06 ,  C07C311/19 ,  C07C2601/08 ,  C07C2601/14 ,  C07D211/34 ,  C07D211/58 ,  C07D213/56 ,  C07D215/22 ,  C07D241/04 ,  C07D333/70 ,  C07D409/12 ,  C07D471/04

Abstract: Compounds of formula (I) inhibit HDAC activity: wherein A, B and D independently represent ═C— or ═N—; W is a divalent radical —CH═CH— or CH2CH2—; 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; z is 0 or 1; and Y, L1, and X1 are as defined in the claims.

Abstract translation: 式（I）的化合物抑制HDAC活性：其中A，B和D独立地表示= C-或= N-; W是二价基团-CH = CH-或CH 2 CH 2 - ; R1是羧酸基团（-COOH）或可被一个或多个细胞内羧酸酯酶水解成羧酸基团的酯基; R2是天然或非天然α氨基酸的侧链; z为0或1; Y，L1和X1如权利要求中所定义。