Pulmocide Limited

Carrick Therapeutics Limited

Plumocide Limited

Cancer Research Technology Limited

Ip2ipo Innovations Limited

Debiopharm International, S.a.

Mihiro Sunose

Kazuhiro Ito

Peter Strong

Thomas Christopher Colley

Garth Rapeport

Stuart Thomas Onions

Peter John Murray

Vincent Gerusz

Matthew McConville

Jason John Shiers

Kamaldeep Kaur Chohan

Brett Stevenson

Alexander Bondke

Damien Francis Philippe Crepin

Anthony G M Barrett

Edward Ainscow

Ashwani Bahl

Juan Bravo

Ash Bahl

Ed Ainscow

Vasileios Tatsis

Danig Pohin

Pierre-Michel Regenass

Matthew Mcconville

Anthony GM Barrett

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain H-APPAMP compounds (referred to herein as 'H-APPAMP compounds') that, inter alia, inhibit cyclin-dependent protein kinases (CDKs), especially CDK12 and/or CDK13, and are selective, for example, for CDK12 and/or CDK13 as compared to CDK7. In addition to selectively inhibiting CDK12 and/or CDK13, the compounds also act as selective Cyclin K degraders thereby removing the key signaling mechanism required for CDK12 and/or CDK13 activation; this confers additional cellular potency and selectivity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK, especially CDK12 and/or CDK13; and to treat disorders including: disorders that are associated with CDK, especially CDK12 and/or CDK13; disorders that result from an inappropriate activity of a CDK, especially CDK12 and/or CDK13; disorders that are associated with CDK mutation, especially CDK12 and/or CDK13 mutation; disorders that are associated with CDK overexpression, especially CDK12 and/or CDK13 overexpression; disorders that are associated with upstream pathway activation of CDK, especially CDK12 and/or CDK13; disorders that are ameliorated by the inhibition of CDK, especially CDK12 and/or CDK13; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; cardiovascular disorders (including atherosclerosis); autoimmune disorders (including rheumatoid arthritis); and disorders caused by dysfunction of translation in cells (including muscular dystrophy). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti estrogen, an anti-androgen, a Her2 blocker, a cytotoxic chemotherapeutic agent, an agent stimulating the immune system, a checkpoint inhibitor, a DNA repair inhibitor, etc.

4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use

A combination therapy including one or more compounds of formula (I): wherein R represents hydrogen, halo, cyano, Chaloalkyl, Chaloalkoxy, or SONRR, Rand Rindependently represent hydrogen or halo; Rrepresents hydrogen, halo, cyano, Calkyl, Calkoxy, or Chaloalkoxy; Rrepresents halo, cyano, Calkyl, or Chydroxyalkyl; Rrepresents hydrogen or Calkyl; X represents CH or N; Y represents N or CH which carbon atom may optionally be substituted by R, Ror R; Rand Rindependently represent hydrogen or Calkyl; or a pharmaceutically acceptable salt thereof; and a second or further active ingredient.

Process for preparing a compound useful to treat mycoses

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino]methyl]piperidin-3-ol compounds (referred to herein as “APPAMP compounds”) that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; cardiovascular disorders (including atherosclerosis); and autoimmune disorders (including rheumatoid arthritis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.

4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino]methyl]piperidin-3-ol compounds as CDK inhibitors

A process for preparing a compound of formula (II): includes reacting a compound of formula (VIII): with a compound of formula (XIV): 

This invention relates to compounds which are used in the preparation of the compound of formula (I).

Compounds which are used in the preparation of the compound of formula (I)

A process for preparing a compound of formula (II):  includes reacting a compound of formula (VIII):  with a compound of formula (XIV): 

This invention relates to compounds which are used in the preparation of the compound of formula (II).

Compounds which are used in the preparation of the compound of formula (II)

A process for preparing a compound of formula (I): includes reacting a compound of formula (II): with a compound of formula (III): 

The invention relates to aqueous suspension formulations of compounds, as defined in the specification and as represented by the compound of formula (I): and to their use in therapy.

Aqueous suspension formulation comprising 4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluoro-phenyl)tetrahydrofuran-3-yl)methoxy)-3-methylphenyl) or a pharmaceutically acceptable salt thereof

A compound of formula (II): or a compound of formula (IV): or a compound of formula (XX): is useful in the treatment of mycoses.

Compound useful to treat mycoses

A process for preparing a compound of formula (I): or a pharmaceutically acceptable salt thereof includes reacting a compound of formula (6): (wherein R is H) with 2-aminocyclohexanol or a salt thereof.

Process for preparing 4-(4-(4-(((3R,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluoro-phenyl)tetrahydrofuran-3-yl)methoxy)-3-methylphenyl)piperazin-1-yl)-N-((1S,2S)-2-hydroxycyclohexyl) benzamide or a pharmaceutically acceptable salt thereof

This invention relates to compounds, as defined in the specification and as represented by the compound of formula (I): that are useful in the treatment of mycoses, compositions containing them and their use in therapy.

This invention relates to a compound, as defined in the specification and as represented by the compound of formula (I): useful in the treatment of mycoses, to compositions containing it and its use in therapy.

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Nottingham, United Kingdom

Mihiro Sunose