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US 2024/0174676 A1Published application
Pyrazolopyrimidine compounds as kinase Inhibitors
AssigneePrincipia Biopharma Inc.
InventorsTim Owens, Erik Verner
Life of this patent
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Abstract
The present disclosure provides compounds and/or pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BTK, and are potentially useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as cancer, inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and/or pharmaceutically acceptable salts thereof and processes for preparing such compounds and pharmaceutically acceptable salts thereof.
Claims8
1-44. (canceled)
A process of preparing a compound of Formula (IA):
- (IA), or a pharmaceutically salt thereof,
- wherein:
- —Z— is:
- and
- Rc is:
- (a) —C(CH3)2-(4-R4-piperazin-1-yl) wherein R4 is hydrogen, alkyl, alkoxyalkyl, haloalkyl, alkylsulfonyl, alkoxycarbonyl, acyl, or oxetan-3-yl and the piperazinyl ring is optionally substituted with one or two alkyl;
- (b) —C(CH3)2-(3-oxo-4-Ra-piperazin-1-yl) wherein Ra is hydrogen, alkyl, alkoxyalkyl, haloalkyl, or oxetan-3-yl and the piperazinyl ring is optionally substituted with one or two alkyl;
- (c) —C(CH3)2—NRboxetan-3-yl wherein Rb is hydrogen, alkyl, or cycloalkyl;
- (d) —C(CH3)2—Rc wherein Rc is
- wherein one or two of X1, X2 and X3 are nitrogen and the rest are carbon, and wherein the ring is optionally substituted with one or two substituents independently selected from alkyl, haloalkyl, or halo;
- or
- (e) —C(CH3)2-2-oxa-6-azaspiro[3.3]heptan-6-yl or —C(CH3)2—CH2morpholine-4-yl;
- the process comprising the steps:
- (a) reacting a compound of formula (1):
- wherein:
- —Z— is as defined above;
- with an aldehyde of formula RcCHO wherein Rc is as defined above;
- or
- (b) reacting a compound of formula (2):
- wherein:
- —Z— is as defined above;
- with a compound of formula RcCH═C(CN)CO2H or RcCH═C(CN)COX wherein Rc is as defined above and X is a leaving group capable of being displaced by the nitrogen atom of the Z group under amide coupling reaction conditions;
- (c) optionally making an acid addition salt of a compound obtained from steps (a) or (b) above;
- (d) optionally making a free base of a compound obtained from steps (a), (b), or (c) above;
- (e) optionally separating individual stereoisomers of the compounds obtained from steps (a), (b), (c), or (d) above;
- and
- (f) optionally separating individual (E) and (Z) isomers of the compounds obtained from steps (a), (b), (c), (d), or (e) above.
24 more elements
Dependencies are inferred from the claim text.