Hoffmann-la Roche Inc.

Monte Rosa Therapeutics Ag

Monte Rosa Therapeutics, Inc.

F. Hoffmann-la Roche Ag

Bernhard Fasching

Patrick Schnider

Cosimo Dolente

Valerie Runtz-Schmitt

Hans Hilpert

Carsten Kroll

Adrian Schaeublin

Claudia Zampaloni

Sabine Kolczewski

Konrad H Bleicher

Hong Shen

Alexander Alanine

Theodor Stoll

Amal Wahhab

Helmut Thomas

Dwight MacDonald

Stephen Jackson

Julien Beignet

Taishan Hu

Alexander Flohr

Thomas Ryckmans

Emmanuel Pinard

Henner Knust

Andrew William Thomas

Bernd Buettelmann

Katrin Groebke Zbinden

Kurt E Amrein

Giuseppe Cecere

Andreas Koblet

Maria-Clemencia Hernandez

Laura Ann McAllister

Andreas Ritzén

Konrad Bleicher

Laura Mcallister

Elisa Liardo

Freya Harvey

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that degrade and/or otherwise modulate (e.g., inhibit) NIMA Related Kinase 7 (NEK7). Said chemical entities are useful, e.g., for treating a subject (e.g., a human subject) having one or more disorders or diseases associated with NLRP3 inflammasome activation. Said disorders or diseases include but are not limited to, autoinflammatory and autoimmune disorders (e.g., gout, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease), cardiovascular and metabolic disorders (eg. pericarditis, atherosclerosis, Type 2 diabetes, obesity, and metabolic syndrome), fibrotic disorders (e.g. interstitial lung disease, chronic kidney disease), hematology (eg, anemia of inflammation) and eye disorders (eg. macular degeneration). In embodiments, and while not wishing to be bound by theory, it is believed that the chemical entities described herein directly target (e.g., directly bind to) NEK7, thereby altering (e.g., attenuating) the inflammatory response modulated by the NLRP3 inflammasome. This disclosure also features compositions containing the same as well as methods of using and making the same.

Targeted protein degradation

Disclosed herein are compound or pharmaceutically acceptable salts or stereoisomers thereof of formula I: Xis linear or branched Calkyl, Ccycloalkyl, Caryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein Xis unsubstituted or substituted with one or more of halogen, linear or branched Calkyl, linear or branched Cheteroalkyl, CF, CHF, CMeF, —O—CHF, —O—(CH)—OMe, OCF, Calkylamino, —CN, —N(H)C(O)—Calkyl, —OC(O)—Calkyl, —OC(O)—Calkylamino, —C(O)O—Calkyl, —COOH, —CalkylC(O)OH, —CalkylC(O)O—Calkyl, NH, Calkoxy, Calkylhydroxy, —CHF, —N(H)C(O)—O—Calkyl, and C(OH)(CF); or Xtogether with the N atom of the carbamate forms a 4-8 membered heterocycloalkyl, which is unsubstituted or substituted with one or more of halogen, linear or branched —Calkyl, CF, CHF, CMeF, —O—(CH)—OMe, OCF, OCHF, Calkylamino, —CN, —N(H)C(O)—Calkyl, —OC(O)—Calkyl, —C(O)O—Calkyl, —COOH, —CalkylC(O)OH, —CalkylC(O)O—Calkyl, NH, Calkylhydroxy, and Calkoxy; Xis H, Ccycloalkyl, Caryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein Xis unsubstituted or substituted with one or more of linear or branched Calkyl, —Calkoxy, NH, NMe, halogen, CF, CHF, CMeF, —O—(CH)—OMe, OCF, OCHF, and Calkylhydroxy; Lis a covalent bond, linear or branched Calkyl; Lis a covalent bond, linear or branched Calkyl; and Lis a covalent bond, linear or branched Calkyl, —O—, or —Calkoxy, wherein linear or branched Calkyl is unsubstituted or substituted with one or more of halogen. Disclosed herein is also their use as modulators of cereblon, methods of preparation of these compounds, compositions comprising these compounds, and methods of using them in the treatment of abnormal cell growth in mammals, especially humans.

Isoindolinone compounds

The present invention provides spiro-oxazolones, which act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The present compounds are useful as therapeutics acting peripherally and centrally in the conditions of inappropriate secretion of vasopressin, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, aggressive behavior and phase shift sleep disorders, in particular jetlag.

Spiro-oxazolones

The present invention provides compounds of formula (I)

Peptide macrocycles against

The present invention provides compounds of formula (I) 

Peptide macrocycles against Acinetobacter baumannii

Compounds having the formula (I) wherein R, R, R, R, R, R, X, Y and Z are as described herein, compositions including the compounds and methods of using the compounds.

Growing community of inventors

Basel, Switzerland

Bernhard Fasching