Fused bicyclic raf inhibitors and methods for use thereof
AssigneeJazz Pharmaceuticals Ireland Limited
InventorsAndrew BELFIELD, Clifford David JONES, Jean-François MARGATHE, Chiara COLLETTO
Life of this patent
Estimating the term…
Abstract
The present disclosure generally relates to improved synthesis of fused bicyclic Raf inhibitors of formula (I), (I-A), (I-B), (II), or (III), or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof. The disclosure also relates to method of using the compound of formula (I), (I-A), (I-B), (II), or (III), or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, for treating diseases such as cancer, including colorectal cancer.
Claims55
A compound of formula (I), or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof,
- wherein:
- ring A is a 5-membered heterocycle or heteroaryl containing 1, 2, or 3, nitrogen atom as a ring member;
- one of R1 or R2 is a substituted C1-8 alkyl, an unsubstituted C5-8 alkyl, a substituted or unsubstituted C1-8 haloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, or a substituted heteroaryl, and the other R1 or R2 is H;
- or alternatively, R1 and R2 together with the atoms to which they are attached forms a 5- or 6-membered saturated, partially unsaturated, or unsaturated ring containing 0, 1, or 2 heteroatoms selected from N, O, or S, wherein the ring is substituted or unsubstituted;
- and
- wherein when ring A is an imidazole, then the substituted aryl is not
- and
- wherein when ring A is an imidazole, R1 and R2 together with the atoms to which they are attached do not form an unsubstituted phenyl ring.
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A compound of formula (II), or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof,
- wherein:
- X1 and X2 are each N or CH;
- R1 is a substituted C1-8 alkyl, an unsubstituted C5-8 alkyl, a substituted or unsubstituted C1-8 haloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, or a substituted or unsubstituted heteroaryl;
- and
- R4 is —NRFC(O)R5, —NRFC(O)CH2R5, —NRFC(O)CH(CH3)R5, or —NRFR5;
- R5 is a substituted or unsubstituted group selected from alkyl, carbocyclyl, aryl, heterocyclyl, or heteroaryl;
- and
- RF is H or C1-3 alkyl.
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A compound of formula (III), or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof,
- wherein:
- R6 is —C(O)NRFR5, —C(O)NRFCH2R5, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heteroaryl;
- R5 is a substituted or unsubstituted group selected from carbocyclyl, aryl, heterocyclyl, or heteroaryl;
- and
- RF is H or C1-3 alkyl.
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Dependencies are inferred from the claim text.