Mission Therapeutics Limited

Cellzome Limited

Janssen Pharmaceutica Nv

Diagnostig Ltd.

Cellzone Limited

Missions Therapeutics Limited

Alison Jones

Martin Stockley

Mark Kemp

Gavin Alistair Whitlock

Karl Richard Gibson

Andrew Madin

Michael David Woodrow

Jeremy Major

Chih Yung Ho

Yan Zhang

Mark Ian Kemp

Nigel Ramsden

Mihiro Sunose

Rosemary Lynch

Richard John Harrison

Svenja Burckhardt

Rita Adrego

Adeline Morel

Laura Convery

Martin Lee Stockley

Mark Stephen Baird

Christopher David Gwenin

Umar S M Maharoof

Vanessa Valerie Gwenin

John Harrison

Keith Allan Menear

Gavin Whitlock

Karl Gibson

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1). The invention further relates to the use of DUB inhibitors in the treatment of cancer and other indications. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R8 are as defined herein.

Compounds

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R, R, R, R, Rand Reach independently represent hydrogen, optionally substituted C-Calkyl or optionally substituted C-Ccycloalkyl, or Rand Rtogether form an optionally substituted C-Ccycloalkyl ring, or Rand Rtogether form an optionally substituted C-Ccycloalkyl ring; Rrepresents hydrogen or optionally substituted C-Calkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.

1-cyano-pyrrolidine derivatives as dub inhibitors

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1). The invention further relates to the use of DUB inhibitors in the treatment of cancer and other indications. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R8 are as defined herein. 

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (II) or a pharmaceutically acceptable salt thereof, wherein R, R, R, R, R, R, R, R, Z, Y and m are as defined herein. 

1-cyano-pyrrolidine compounds as USP30 inhibitors

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R, R, R, R, Rand Reach independently represent hydrogen, optionally substituted C-Calkyl or optionally substituted C-Ccycloalkyl, or Rand Rtogether form an optionally substituted C-Ccycloalkyl ring, or Rand Rtogether form an optionally substituted C-Ccycloalkyl ring; Rrepresents hydrogen or optionally substituted C-Calkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom. 

1-cyano-pyrrolidine derivatives as DUB inhibitors

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of cancer and conditions involving mitochondrial dysfunction. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R, R, R, R, R, R, R, Rand Rare as defined herein.

Cyanopyrrolidines as dub inhibitors for the treatment of cancer

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to the use of DUB or desumoylating inhibitors in the treatment of cancer. Described herein are compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R, R, Rand Reach independently represent hydrogen, optionally substituted C-Calkyl or Rand Rtogether form an optionally substituted C-Ccycloalkyl ring, or Rand Rtogether form an optionally substituted C-Ccycloalkyl ring; A is a 5 membered nitrogen-containing aromatic ring and is substituted with at least one optionally substituted 5 to 10 membered monocyclic or bicyclic heteroaryl or aryl ring attached through an optional linker. 

4,6 dihydropyrrolo [3,4-C] pyrazole-5 (1H)-carbonitrile derivates for treating cancer

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of Cezanne 1. The invention further relates to the use of DUB inhibitors in the treatment of cancer.

Spiro-condensed pyrrolidine derivatives as deubiquitylating enzymes (DUB) inhibitors

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (II) or a pharmaceutically acceptable sat thereof, wherein R, R, R, R, R, R, R, R, R, Z, Y and m are as defined herein. 

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (II) or a pharmaceutically acceptable salt thereof, wherein R, R, R, R, R, R, R, R, R, Z, Y and m are as defined herein. 

The present invention relates to substituted-cyanopyrrolidines of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (I) 

Cyanopyrrolidine derivatives with activity as inhibitors of USP30

A method of determining whether an individual is infected with mycobacteria. The method comprising the steps of (a) providing a system which comprises at least two different mycolic-acid derived antigens; (b) introducing a sample obtained from the individual into the system and into contact with each of the at least two different mycolic-acid derived antigens; and (c) detecting the presence or absence of the binding of a biomarker in the sample with each antigen in the system. The method may be particularly suitable for determining the presence or absence of a disease antibody indicative of infection with any disease caused by infection with mycobacteria, for example, leprosy, pulmonary disease, burili ulcer, Johne's disease and bovine. A kit and device are also described. The present invention may provide an over the counter device to allow individuals to check on a routine basis that they have normal immune responses.

Method and kit for detection of mycobacteria

The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer. 

Growing community of inventors

Cambridge, United Kingdom

Alison Jones