US 10,300,066 B2 · Polyfluorinated compounds acting as bruton tyrosine kinase inhibitors

Abstract

Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.

Claims19

Dependent claims

A compound selected from the group consisting of

1-(3-(4-amino-3-(2-fluoro-4-(2,3,5,6-tetrafluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-en-1-one, or a pharmaceutically acceptable salt thereof;
N-((1s,4s)-4-(4-amino-3-(2-fluoro-4-(3-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl)acrylamide, or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof;
1-((R)-3-(4-amino-3-(2-fluoro-4-(2-fluorobenzoyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-en-1-one, or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof;
1-(3-(4-amino-3-(2-fluoro-4-(3-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-en-1-one, or a pharmaceutically acceptable salt thereof;
and
3-(2-fluoro-4-(2,3,5,6-tetrafluorophenoxy)phenyl)-1-((R)-1-(vinylsulfonyl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine, or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof.

3 more elements

Dependencies are inferred from the claim text.

Polyfluorinated compounds acting as bruton tyrosine kinase inhibitors

Life of this patent

Polyfluorinated compounds acting as bruton tyrosine kinase inhibitors

Life of this patent

Abstract

Claims19