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US 10,239,876 B2Granted
Triaza-spirodecanones as DDR1 inhibitors
AssigneeHoffman-La Roche Inc.
InventorsBernd Buettelmann, Buelent Kocer, Bernd Kuhn, Marco Prunotto, Hans Richter, Martin Ritter, Markus Rudolph, Alexander Lee Satz
Life of this patent
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Abstract
The present invention relates to compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.
Claims25
A compound of formula (I)
- wherein
- L is —(CHR8)m—(CHR9)n—(CO)q—
- R1 is —NR6R7, aryl, or C3-7 cycloalkyl, wherein each of aryl, and C3-7 cycloalkyl and are optionally substituted with one or more R1′;
- each R1′ is independently selected from halogen, cyano, C1-7 alkyl, halo-C17 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C17 alkyl, phenyl, benzyl, amino, hydroxy, C1-7 alkoxy, halo-C1-7 alkoxy, C1-7 alkoxy-C1-7 alkyl, oxo, —CH2—OR16, —C(O)—OR16, —CH2—NHR16, —CH2—CH2—NR17R18, —CH2—C(O)—NHR16 and —C(O)—NHR16;
- or two R1′ together are —(CR12R13)s—;
- R2 is hydrogen, fluorine, C1-7 alkyl, or halo-C1-7 alkyl;
- R3 is hydrogen or C1-7 alkyl;
- R4 is aryl optionally substituted by one or more R4′;
- each R4′ is independently selected from halogen, cyano, C1-7 alkyl, halo-C1-7 alkyl, C3-7 cycloalkyl, amino, hydroxy, C1-7 alkoxy and halo-C1-7 alkoxy;
- R5 is indazole optionally substituted with one or more R5′;
- each R5′ is independently selected from halogen, cyano, C1-7 alkyl, halo-C1-7 alkyl, C3-7 cycloalkyl, amino, hydroxy, C1-7 alkoxy and —C(O)NH2;
- R6 is C1-7 alkyl, halo-C1-7 alkyl, hydroxy-C1-7 alkyl, C1-7 alkoxy-C1-7 alkyl, C3-7 cycloalkyl, aryl, —CH2—CH2—NR17R18, wherein C1-7 alkyl, C3-7 cycloalkyl, aryl or benzyl, are optionally substituted with one or more R6′;
- each R6′ is independently selected from halogen, cyano, C1-7 alkyl, halo-C1-7 alkyl, C3-7 cycloalkyl, amino, hydroxy, C1-7 alkoxy, halo-C1-7 alkoxy, C1-7 alkoxy-C1-7 alkyl, oxo, —CH2—C(O)—NHR16, phenyl, optionally substituted with C1-7 alkyl or benzyl;
- R7 is hydrogen, C1-7 alkyl, C3-7 cycloalkyl or is halo-C1-7 alkyl;
- R8 is hydrogen, C1-7 alkyl, hydroxy-C1-7 alkyl, C1-7 alkoxy-C1-7 alkyl, halo-C1-7 alkoxy-C1-7 alkyl, —(CH2)r-phenyl, or —(CH2)rNR10R11;
- R9 is hydrogen, C1-7 alkyl, or halo-C1-7 alkyl;
- R10 and R11 are independently selected from hydrogen and C1-7 alkyl;
- R12, R13, R14 and R15 are each independently selected from hydrogen, halogen and C1-7 alkyl;
- R16 is hydrogen, C1-7alkyl, halo-C1-7 alkyl or C3-7 cycloalkyl;
- R17 and R18 are independently selected from hydrogen and C1-7 alkyl;
- m is 0, 1 or 2;
- n is 0, 1 or 2;
- q is 0 or 1;
- r is 0, 1 or 2;
- s is 2, 3 or 4;
- or a pharmaceutically acceptable salt thereof;
- with the proviso that if R1 is —NR6R7 then:
- if q=0 then m+n≥2, or
- if q=1 then m+n≥1.
26 more elements
Dependencies are inferred from the claim text.