JPWO2021245055A5

JPWO2021245055A5 -

Info

Publication number: JPWO2021245055A5
Application number: JP2022574317A
Authority: JP
Publication date: 2024-06-10

Claims

Compounds of formula (I)

(Wherein,
R ^1a and R ^1b are both independently selected from the group consisting of hydrogen, C _1-4 alkyl, C _1-4 haloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, halogen, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , C _3-5 cycloalkyl and 3- to 5-membered heterocyclyl;
R ^2a and R ^2b are both independently selected from the group consisting of hydrogen, C _1-4 alkyl, C _1-4 haloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, halogen, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , C _3-5 cycloalkyl and 3- to 5-membered heterocyclyl;
and/or one of R ^1a or R ^1b and one of R ^2a or R ^2b together with the carbon atom to which they are attached may form a cyclopropane ring;
Z is --(CR ^6a R ^6b ) _n --,
R ^6a and R ^6b are each independently selected from the group consisting of hydrogen, C _1-4 alkyl, C _1-4 haloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, halogen, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , C _3-5 cycloalkyl and 3- to 5-membered heterocyclyl;
n is selected from the group consisting of 0, 1 and 2;
^R3 is selected from the group consisting of hydrogen, _C1-6 alkyl, _{C1-6 haloalkyl, C1-6} alkoxy, _C1-6 haloalkoxy, cyano _-C1-6 _alkyl , halogen, -OH, _-NH2 , -NH( _C1-4 alkyl), -N( _C1-4 alkyl) ₂ , -CN, _C3-5 cycloalkyl and 3- to 5-membered heterocyclyl;
Ring A is oxadiazole or thiadiazole;
U is selected from the group consisting of nitrogen (=N--) and carbon substituted with ^R (=C(R ^A )--);
V is selected from the group consisting of nitrogen (=N--) and carbon substituted with R ^B (=C(R ^B )--);
W is selected from the group consisting of nitrogen (=N--) and carbon substituted with ^R (=C( ^R )--);
R ^A , R ^B and R ^C are hydrogen, C _1-6 haloalkyl, C _2-6 alkynyl (optionally substituted by C _3-5 cycloalkyl), C _1-6 alkoxy, C _1-6 haloalkoxy, halogen, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(═O)NH ₂ , -C(═O)NH(C _1-4 alkyl), -C(═O)N(C _1-4 alkyl) ₂ , -S-C _1-6 alkyl, -S(═O) ₂ -C _1-6 alkyl, C _3-5 cycloalkyl, 3- to 5-membered heterocyclyl and C _1-6 alkyl (C _1-6 alkoxy, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O) _NH2 , -C(=O)NH( _C1-4 alkyl) and -C(=O)N( _C1-4 alkyl) ₂ ;
^R5 is selected from the group consisting of R ^a1 and R ^b1 ;
R ^a1 is selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl, and C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl are all optionally substituted by one or more of the same or different R ^b1 and/or R ^c1 ;
each R ^b1 is independently selected from the group consisting of -OR ^c1 , -NR ^c1 R ^c1 , halogen, -CN, -C(=O)R ^c1 , -C(=O)OR ^c1 , -C(=O)NR ^c1 R ^c1 , -S(=O) ₂ R ^c1 , -S(=O) ₂ NR ^c1 R ^c1 , -NHC(=O)R ^c1 , -N(C _1-4 alkyl)C(=O)R ^c1 , -NHS(=O) ₂ R ^c1 , -N(C _1-4 alkyl)S(=O) ₂ R ^c1 , -NHC(=O)OR ^c1 , -N(C _1-4 alkyl)C(=O)OR ^c1 and the divalent substituent =O;
each R ^c1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl, wherein C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl are all optionally substituted by one or more of the same or different R ^d1 and/or R ^e1 ;
each R ^d1 is independently selected from the group consisting of -OR ^e1 , -NR ^e1 R ^e1 , halogen, -CN, -C(=O)R ^e1 , -C(=O)OR ^e1 , -C(=O)NR ^e1 R ^e1 , -S(=O) ₂ R ^e1 , -S(=O) ₂ NR ^e1 R ^e1 , -NHC(=O)R ^e1 , -N(C _1-4 alkyl)C(=O)R ^e1 , -NHS(=O) ₂ R ^c1 , -N(C _1-4 alkyl)S(=O) ₂ R ^c1 , -NHC(=O)OR ^e1 , -N(C _1-4 alkyl)C(=O)OR ^e1 and the divalent substituent =O;
Each R ^e1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl, and C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl are all independently selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl (optionally substituted by one or more of the same or different C _1-4 alkyl), C optionally substituted by one or more identical or different substituents selected from the group consisting of _6-10 aryl, 5-10 membered heteroaryl, -OH, C _1-6 alkoxy, C _1-4 alkoxy-C _1-4 alkyl, hydroxy-C _1-4 alkyl, halogen, -CN, -NH ₂ , -C(═O)C _1-4 alkyl, -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ and the divalent substituent ═O;
L is -L ¹ -L ² -L ³ -, L ¹ is linked to E;
L ¹ is selected from the group consisting of a bond, -NH-, -N(C _1-4 alkyl)-, -O-, -C(=O)-, -NH-C(=O)-, -N(C _1-4 alkyl)-C(=O)-, -C(=O)-NH-, -C(=O)-N(C _1-4 alkyl)-, -C(=O)-, C _1-6 alkylene, C _3-7 cycloalkylene, phenylene, 4- to 12-membered heterocyclylene, and 5- to 10-membered heteroarylene;
^L2 is selected from the group consisting of _C1-6 alkylene, _C3-7 cycloalkylene, phenylene, 4- to 12-membered heterocyclylene, and 5- to 10-membered heteroarylene;
^L3 is selected from the group consisting of a bond, -NH-, -N( _C1-4 alkyl)-, -O-, -C(=O)-, -NH-C(=O)-, -N( _C1-4 alkyl)-C(=O)-, -C(=O)-NH-, -C(=O)-N( _C1-4 alkyl)-, -C(=O)-, _C1-6 alkylene, _C3-7 cycloalkylene, phenylene, 4- to 12-membered heterocyclylene, and 5- to 10-membered heteroarylene;
C _1-6 alkylene, C _3-7 cycloalkylene, phenylene, 4- to 12-membered heterocyclylene and 5- to 10-membered heteroarylene in L ¹ , L ² and L ³ are each independently C _2-6 alkynyl, C _1-6 haloalkyl, C _3-7 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, halogen, -OH, -CN, C _1-6 alkoxy, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(═O)OH, -C(═O)-OC _1-6 alkyl, -C(═O)NH ₂ , -C(═O)NH(C _1-4 alkyl), -C(═O)N(C _1-4 alkyl) ₂ , divalent substituents ═O and C _1-6 alkyl(halogen, -OH, -CN, C _1-4 alkoxy, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O)OH, -C(=O)-OC _1-6 alkyl, -C(=O)NH ₂ , -C(=O)NH(C _1-4 alkyl) and -C(=O)N(C _1-4 alkyl) ₂ ),
E is,

and

represents a double bond or a triple bond,
Q ¹ is selected from the group consisting of a bond, —CH ₂ —, —CH(OH)—, —C(═O)—, —C(═O)N(R ^G1 )—, —C(═O)O—, —S(═O) ₂ —, —S(═O) ₂ N(R ^G1 )—, and —C(═NR ^H1 )—;
each R ^G1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, hydroxy-C _1-6 alkyl, H ₂ N—C _1-6 alkyl, cyano-C _1-6 alkyl, (C _1-4 alkyl)HN—C _1-6 alkyl, (C _1-4 alkyl) ₂ N—C _1-6 alkyl, C _1-6 alkoxy-C _1-6 alkyl, C _3-7 cycloalkyl, and 3- to 11-membered heterocyclyl;
Each R ^H1 is independently selected from the group consisting of hydrogen, —OH, C _1-6 alkoxy, —CN, and C _1-6 alkyl;

When represents a double bond,
R ^D is selected from the group consisting of hydrogen, C _3-7 cycloalkyl, phenyl, halogen, -CN, C _1-6 alkoxy, -C(=O)O-C _1-6 alkyl, -NHC(=O)-C _1-6 alkyl and C _1-6 alkyl (optionally substituted by one or more identical or different _substituents selected from the group consisting of phenyl, 3- to 11-membered heterocyclyl, C _1-6 alkoxy, halogen, -OH, -NH ₂ , -NH(C _1-6 alkyl), -N(C _1-6 alkyl) ₂ , -C(=O)OH, -C(=O)O-C _1-6 alkyl, -C(=O)NH(C _1-6 alkyl), -NHC(=O)-C _1-6 alkyl, -OC(=O)-C 1-6 alkyl and phenyl-C _1-6 alkoxy);
^R and ^R are each independently selected from the group consisting of ^R and ^R ;
R ^a2 is selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11 _- membered heterocyclyl, C _6-10 aryl and _5- to 10-membered heteroaryl, all of which are optionally substituted by one or more _of _the same or different R ^b2 and/or R ^c2 ;
each R ^b2 is independently selected from the group consisting of -OR ^c2 , -NR ^c2 R ^c2 , halogen, -CN, -C(=O)R ^c2 , -C(=O)OR ^c2 , -C(=O)NR ^c2 R ^c2 , -S(=O) _2R ^c2 , -S(=O) _2NR ^c2 R ^c2 , -NHC(=O)R ^c2 , -N(C _1-4 alkyl)C(=O)R ^c2 , -NHC(=O)OR ^c2 , -N(C _1-4 alkyl)C(=O)OR ^c2 and the divalent substituent =O;
Each R ^c2 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl, and 5- to 10-membered heteroaryl, and all of C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _4-10 cycloalkenyl, 3- to 11-membered heterocyclyl, C _6-10 aryl, and 5- to 10-membered heteroaryl are C _1-6 alkyl, C _1-6 alkoxy, halogen, -OH, -C(=O)OH, -C(=O)O-C _1-6 alkyl, -C(=O)C _1-6 alkyl, -C(=O)NH ₂ , -C(=O)NH(C _1-6 alkyl), -C(=O)N(C _1-6 alkyl) ₂ and the divalent substituent =O,
or R ^D and R ^E together with the carbon atom to which they are attached form a 4- to 7-membered unsaturated alicyclic ring or a 4- to 7-membered unsaturated heterocyclic ring, which in addition to R ^F is optionally substituted by one or more identical or different substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, -OH, C _1-6 alkoxy, C _1-4 alkoxy-C _1-4 alkyl, -NH ₂ , -CN, -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , halogen, -C(═O)O-C _1-6 alkyl, and the divalent substituent ═O;
or when ^Q1 is -C(=O)N(R ^G1 )-, R ^G1 and R ^F of -C(=O)N(R ^G1 )- together form a linker selected from the group consisting of -C(=O)-, -CH ₂ -, -CH ₂ -C(=O)-, -C(=O)-CH ₂ - and -C ₂ H ₄ -;

When represents a triple bond,
^Both R and ^R are absent;
^R is ^R ;
R ^a2 is selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11 _- membered heterocyclyl, C _6-10 aryl and _5- to 10-membered heteroaryl, all of which are optionally substituted by one or more _of _the same or different R ^b2 and/or R ^c2 ;
each R ^b2 is independently selected from the group consisting of -OR ^c2 , -NR ^c2 R ^c2 , halogen, -CN, -C(=O)R ^c2 , -C(=O)OR ^c2 , -C(=O)NR ^c2 R ^c2 , -S(=O) _2R ^c2 , -S(=O) _2NR ^c2 R ^c2 , -NHC(=O)R ^c2 , -N(C _1-4 alkyl)C(=O)R ^c2 , -NHC(=O)OR ^c2 , -N(C _1-4 alkyl)C(=O)OR ^c2 and the divalent substituent =O;
Each R ^c2 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl, and 5- to 10-membered heteroaryl;
Or E is

and
^Q2 is selected from the group consisting of a bond, _-CH2- , -CH(OH)-, -C(=O)-, -C(=O)N(R ^G2 )-, -C(=O)O-, -S(=O) _2- , -S(=O) _2N (R ^G2 )- and -C(=NR ^H2 )-;
each R ^G2 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, hydroxy-C _1-6 alkyl, H ₂ N—C _1-6 alkyl, cyano-C _1-6 alkyl, (C _1-4 alkyl)HN—C _1-6 alkyl, (C _1-4 alkyl) ₂ N—C _1-6 alkyl, C _1-6 alkoxy-C _1-6 alkyl, C _3-7 cycloalkyl, and 3- to 11-membered heterocyclyl;
Each R ^H2 is independently selected from the group consisting of hydrogen, —OH, C _1-6 alkoxy, —CN, and C _1-6 alkyl;
R ^I is selected from the group consisting of hydrogen and halogen;
R ^J is hydrogen, or R ^I and R ^J together with the carbon atom to which they are attached form a cyclopropane or oxirane ring;
R ^K is selected from the group consisting of hydrogen, C _1-6 alkyl, —CN and halogen;
R ^L is selected from the group consisting of hydrogen, C _1-6 alkyl, —CN, halogen and —C(═O)—C _1-6 alkyl;
Or E is

and
^Q3 is selected from the group consisting of -C(=O)-, -C(=O)N(R ^G3 )-, -C(=O)O-, -S(=O) ₂ -, -S(=O) ₂ N(R ^G3 )- and -C(=NR ^H3 )-;
each R ^G3 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, hydroxy-C _1-6 alkyl, H ₂ N—C _1-6 alkyl, cyano-C _1-6 alkyl, (C _1-4 alkyl)HN—C _1-6 alkyl, (C _1-4 alkyl) ₂ N—C _1-6 alkyl, C _1-6 alkoxy-C _1-6 alkyl, C _3-7 cycloalkyl, and 3- to 11-membered heterocyclyl;
Each R ^H3 is independently selected from the group consisting of hydrogen, —OH, C _1-6 alkoxy, —CN, and C _1-6 alkyl;
R ^M is selected from the group consisting of halogen, -CN and -O-C(=O) _{-Ci_6alkyl} ;
Or E is

and
^Q4 is selected from the group consisting of a bond, -C(=O)-, -C(=O)O-, -C(=O)NH-, -C(=O)N(C _1-4 alkyl)-, -S(=O) ₂ - and -S(=O) ₂ NH-;
Ring B is selected from the group consisting of phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, and 5-membered heteroaryl;
q is selected from the group consisting of 1, 2, 3, and 4;
Each R ^N is independently selected from the group consisting of C _1-4 alkyl, C _1-4 haloalkyl, vinyl, ethynyl, halogen, —CN, nitro, and C _1-4 alkoxy.
Or its salt.

2. The compound or salt of claim 1 having the formula (Ia):

(Wherein,
^R1a , ^R1b , ^R2a , ^R2b , Z, ^R3 , U, V, W, ^R5 , L and E are defined as in claim 1.

Compound of formula (II)

(Wherein,
R ^1a , R ^1b , R ^2a , R ^2b , Z, R ³ , ring A, U, V, W, R ⁵ and L are defined as in formula (I) in claim 1, and L ¹ in -L ¹ -L ² -L ³ - is linked to the hydrogen of the group H-L- ) or a salt thereof.

R ^1a and R ^1b are both independently selected from the group consisting of hydrogen and C _1-4 alkyl;
R ^2a and R ^2b are both independently selected from the group consisting of hydrogen and halogen;
The compound or salt according to any one of claims 1 to 3.

^R3 is selected from the group consisting of hydrogen, _C1-4 alkyl, _C1-4 haloalkyl, C1-4 alkoxy, _C1-4 haloalkoxy, cyano _-C1-4 _alkyl , halogen, -OH, _-NH2 , -NH( _C1-4 alkyl), -N( _C1-4 alkyl) ₂ and -CN;
The compound or salt according to any one of claims 1 to 4.

Ring A is

Selected from the group consisting of:
The compound or salt according to any one of claims 1 to 5.

U is a carbon substituted by ^R (=C( ^R )--),
V is a carbon substituted by R ^B (=C(R ^B )--);
W is nitrogen (=N-),
R ^A and R ^B are hydrogen, C _1-6 haloalkyl, C _2-6 alkynyl (optionally substituted by C _3-5 cycloalkyl), C _1-6 alkoxy, C _1-6 haloalkoxy, halogen, -CN, -OH, -NH ₂ , -NH(C _{1-4 alkyl), -N(C 1-4} _alkyl ) ₂ , -C(=O)NH ₂ , -C(=O)NH(C _1-4 alkyl), -C(=O)N(C _1-4 alkyl) ₂ , C _3-5 cycloalkyl, 3- to 5-membered heterocyclyl and C _1-6 alkyl (C _1-6 alkoxy, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O)NH ₂ , -C(=O)NH(C each independently selected from the group consisting of -C(=O)N(C _1-4 alkyl) and -C(=O)N(C _1-4 alkyl) ₂ ;
The compound or salt according to any one of claims 1 to 6.

U is a carbon substituted by ^R (=C( ^R )--),
V is a carbon substituted by R ^B (=C(R ^B )--);
W is a carbon substituted with ^R (=C( ^R )--);
R ^A , R ^B and R ^C are hydrogen, C _1-6 haloalkyl, C _2-6 alkynyl (optionally substituted by C _3-5 cycloalkyl), C _1-6 alkoxy, C _1-6 haloalkoxy, halogen, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(═O)NH ₂ , -C(═O)NH(C _1-4 alkyl), -C(═O)N(C _1-4 alkyl) ₂ , C _3-5 cycloalkyl, 3- to 5-membered heterocyclyl and C _1-6 alkyl(C _1-6 alkoxy, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ _, -C(═O)NH(C each independently selected from the group consisting of -C(=O)N(C _1-4 alkyl) and -C(=O)N(C _1-4 alkyl) ₂ ;
The compound or salt according to any one of claims 1 to 6.

U is nitrogen (=N-),
V is a carbon substituted by R ^B (=C(R ^B )--);
W is nitrogen (=N-),
R ^B is hydrogen, C _1-6 haloalkyl, C _2-6 alkynyl (optionally substituted by C _3-5 cycloalkyl), C _1-6 alkoxy, C _1-6 haloalkoxy, halogen, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O)NH ₂ , -C(=O)NH(C _1-4 alkyl), -C(=O)N(C _1-4 alkyl) ₂ , C _3-5 cycloalkyl, 3- to 5-membered heterocyclyl and C _1-6 alkyl (C _1-6 alkoxy, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O)NH ₂ , -C(=O)NH(C _1-4 alkyl) and -C(=O)N(C _1-4 alkyl) ₂ ) which may be substituted by a substituent selected from the group consisting of
The compound or salt according to any one of claims 1 to 6.

U is a carbon substituted by ^R (=C( ^R )--),
V is nitrogen (=N-),
W is nitrogen (=N-),
R ^A is hydrogen, C _1-6 haloalkyl, C _2-6 alkynyl (optionally substituted by C _3-5 cycloalkyl), C _1-6 alkoxy, C _1-6 haloalkoxy, halogen, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O)NH ₂ , -C(=O)NH(C _1-4 alkyl), -C(=O)N(C _1-4 alkyl) ₂ , C _3-5 cycloalkyl, 3- to 5-membered heterocyclyl and C _1-6 alkyl (C _1-6 alkoxy, -CN, -OH, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O)NH ₂ , -C(=O)NH(C _1-4 alkyl) and -C(=O)N(C _1-4 alkyl) ₂ ) which may be substituted by a substituent selected from the group consisting of
The compound or salt according to any one of claims 1 to 6.

U is nitrogen (=N-),
V is nitrogen (=N-),
W is nitrogen (=N-);
The compound or salt according to any one of claims 1 to 6.

^R5 is selected from the group consisting of R ^a1 and R ^b1 ;
R ^a1 is selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkynyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl, and all of C _1-6 alkyl, C _1-6 haloalkyl, C _2-6 alkynyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted by one or more of the same or different R ^b1 and/or R ^c1 ;
each R ^b1 is independently selected from the group consisting of -OR ^c1 , -NR ^c1 R ^c1 , halogen, -CN, -C(=O)R ^c1 , -C(=O)OR ^c1 , -C(=O)NR ^c1 R ^c1 , -S(=O) ₂ R ^c1 , -S(=O) ₂ NR ^c1 R ^c1 , -NHC(=O)R ^c1 , -N(C _1-4 alkyl)C(=O)R ^c1 and the divalent substituent =O;
each R ^c1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl, and 5- to 10-membered heteroaryl, and all of the C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl, and 5- to 10-membered heteroaryl are optionally substituted by one or more of the same or different R ^d1 and/or R ^e1 ;
each R ^d1 is independently selected from the group consisting of -OR ^e1 , -NR ^e1 R ^e1 , halogen, -CN, -C(=O)R ^e1 , -C(=O)NR ^e1 R ^e1 , and the divalent substituent =O;
each R ^e1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl, and all of C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl are C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl (optionally substituted by one or more of the same or different C _1-4 alkyl), C _6-10 aryl, 5- to 10-membered heteroaryl, -OH, C _1-6 alkoxy, C _1-4 alkoxy-C _1-4 alkyl, hydroxy-C _1-4 alkyl, halogen, -CN, -NH ₂ , -C(═O)C may be substituted by one or more identical or different substituents selected from the group consisting of _1-4 alkyl, -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ and the divalent substituent =O;
A compound or salt according to any one of claims 1 to 11.

^R5 is R ^a1 ,
R ^a1 is selected from the group consisting of 3- to 11-membered heterocyclyl and 5- to 10-membered heteroaryl, all of which are optionally substituted by one or more of the same or different R ^b1 and/or R ^c1 ;
each R ^b1 is independently selected from the group consisting of -OR ^c1 , -NR ^c1 R ^c1 , halogen, -C(=O)OR ^c1 , and the divalent substituent =O;
each R ^c1 is independently selected from _the group _consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, and _3-11 membered heterocyclyl, all of which are optionally substituted by one or more of the same or different R ^d1 and/or R ^e1 ;
each R ^d1 is independently selected from the group consisting of -OR ^e1 , -NR ^e1 R ^e1 and halogen;
each R ^e1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _3-10 cycloalkyl, and 3- to 11-membered heterocyclyl, and all of the C _1-6 alkyl, C _3-10 cycloalkyl, and 3- to 11-membered heterocyclyl are optionally substituted by one or more identical or different substituents selected from the group consisting of C _1-6 alkyl and 3- to 11-membered heterocyclyl (optionally substituted by one or more identical or different C _1-4 alkyl);
A compound or salt according to any one of claims 1 to 11.

^R5 is R ^b1 ,
R ^b1 is independently selected from the group consisting of -OR ^c1 and -NR ^c1 R ^c1 ;
each R ^c1 is independently selected from the group consisting of hydrogen, C _1-6 _alkyl , C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 _aryl , and 5- to 10-membered heteroaryl, all of which are optionally substituted by one or more _of the same or different R ^d1 and/or R ^e1 ;
each R ^d1 is independently selected from the group consisting of -OR ^e1 , -NR ^e1 R ^e1 , halogen, -C(=O)R ^e1 and -C(=O)NR ^e1 R ^e1 ;
R ^e1 is each independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl, and C _1-6 alkyl, C _3-10 cycloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl are all optionally substituted by one or more identical or different substituents selected from the group consisting of C _1-6 alkyl, C _1-6 haloalkyl, 3- to 11-membered heterocyclyl (optionally substituted by one or more identical or different C _1-4 alkyl), C _1-6 alkoxy, halogen and the divalent substituent =O;
A compound or salt according to any one of claims 1 to 11.

L is -L ¹ -L ² -L ³ -, L ¹ is linked to E;
L ¹ is selected from the group consisting of a bond, C _1-6 alkylene, and 4- to 12-membered heterocyclylene;
^L2 is selected from the group consisting of _C1-6 alkylene, phenylene, and 4- to 12-membered heterocyclylene;
^L3 is selected from the group consisting of a bond, -NH-, -N(C _1-4 alkyl)- and -O-;
C _1-6 alkylene, phenylene and 4-12 membered heterocyclylene in L ¹ and L ² are respectively C _2-6 alkynyl, C _1-6 haloalkyl, C _3-7 cycloalkyl, phenyl, 5-6 membered heteroaryl, halogen, -OH, -CN, C _1-6 alkoxy, -NH ₂ , -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(═O)OH, -C(═O)-OC _1-6 alkyl, -C(═O)NH ₂ , -C(═O)NH(C _1-4 alkyl), -C(═O)N(C _1-4 alkyl) ₂ , divalent substituents ═O and C _1-6 alkyl(halogen, -OH, -CN, -NH ₂ , C _1-4 alkoxy, -NH(C _1-4 alkyl), -N(C _1-4 alkyl) ₂ , -C(=O)OH, -C(=O)-OC _1-6 alkyl, -C(=O)NH ₂ , -C(=O)NH(C _1-4 alkyl) and -C(=O)N(C _1-4 alkyl) ₂ ),
The compound or salt according to any one of claims 1 , 2, 4 to 14.

L,

Selected from the group consisting of:
16. A compound or salt according to claim 15.

E.

and
Q ¹ is selected from the group consisting of -CH ₂ -, -C(=O)-, -C(=O)N(R ^G1 )-, -C(=O)O-, -S(=O) ₂ -, -S(=O) ₂ N(R ^G1 )- and -C(=NR ^H1 )-;
Each R ^G1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, and hydroxy-C _1-6 alkyl;
each R ^H1 is independently selected from the group consisting of hydrogen, —OH, C _1-6 alkoxy, —CN, and C _1-6 alkyl;
R ^D is selected from the group consisting of hydrogen, C _3-7 cycloalkyl, phenyl, halogen, -CN, C _1-6 alkoxy, -C(=O)O-C _1-6 alkyl and C _1-6 alkyl (optionally substituted by one or more identical or different substituents _selected from the group consisting of phenyl, 3- to 11-membered heterocyclyl, C _1-6 alkoxy, halogen, -OH, -N(C _1-6 alkyl) ₂ , -C(=O)OH, -C(=O)O-C _1-6 alkyl, -C(=O)NH(C _1-6 alkyl), -NHC(=O)-C _1-6 alkyl, -OC(=O)-C _{1-6 alkyl and phenyl-C 1-6} alkoxy);
^R and ^R are each independently selected from the group consisting of ^R and ^R ;
R ^a2 is selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, C _3-10 cycloalkyl, 3- to 11 _- membered heterocyclyl, C _6-10 aryl and _5- to 10-membered heteroaryl, all of which are optionally substituted by one or more _of _the same or different R ^b2 and/or R ^c2 ;
each R ^b2 is independently selected from the group consisting of -OR ^c2 , -NR ^c2 R ^c2 , halogen, -CN, -C(=O)OR ^c2 , -C(=O)NR ^c2 R ^c2 , -NHC(=O)R ^c2 , -N(C _1-4 alkyl)C(=O)R ^c2 , -NHC(=O)OR ^c2 and -N(C _1-4 alkyl)C(=O)OR ^c2 ;
R ^c2 is each independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl, and C _1-6 alkyl, C _1-6 haloalkyl, 3- to 11-membered heterocyclyl, C _6-10 aryl and 5- to 10-membered heteroaryl are all optionally substituted by one or more identical or different substituents selected from the group consisting of C _1-6 alkyl, C _1-6 alkoxy, halogen, -OH, -C(=O)OH, -C(=O)O-C _1-6 alkyl, -C(=O)C _1-6 alkyl, -C(=O)NH ₂ , -C(=O)NH(C _1-6 alkyl), -C(=O)N(C _1-6 alkyl) ₂ and the divalent substituent =O;
A compound or salt according to any one of claims 1 , 2, 4 to 16.

E.

Selected from the group consisting of:
18. A compound or salt according to claim 17.

E.

and
Q ¹ is selected from the group consisting of -CH ₂ -, -C(=O)-, -C(=O)N(R ^G1 )-, -C(=O)O-, -S(=O) ₂ -, -S(=O) ₂ N(R ^G1 )- and -C(=NR ^H1 )-;
Each R ^G1 is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _1-6 haloalkyl, and hydroxy-C _1-6 alkyl;
each R ^H1 is independently selected from the group consisting of hydrogen, —OH, C _1-6 alkoxy, —CN, and C _1-6 alkyl;
R ^F is selected from the group consisting of hydrogen and C _1-6 alkyl (optionally substituted by a substituent selected from the group consisting of -OH, C _1-6 alkoxy, -NH ₂ , -NH(C _1-4 alkyl) and -N(C _1-4 alkyl) ₂ );
The compound or salt according to any one of claims 1 , 2, 4 to 16.

E.

Selected from the group consisting of:
20. A compound or salt according to claim 19.

2. The compound according to claim 1, or a salt thereof, selected from the group consisting of:

The compound or salt thereof according to claim 3, which is selected from the group consisting of:

A pharmaceutical composition comprising the compound according to any one of claims 1 to 22 or a pharma- ceutically acceptable salt thereof.

A pharmaceutical composition comprising a compound according to any one of claims 1 to 22 or a pharma- ceutically acceptable salt thereof for use in the treatment and/or prevention of cancer.

25. A pharmaceutical composition for use according to any one of claims 23 and 24, wherein the compound or salt is administered before, after or together with one or more other pharmacologically active substances.

25. A pharmaceutical composition for use according to any one of claims 23 and 24 , wherein the compound or salt is administered in combination with one or more other pharmacologically active substances.

The pharmaceutical composition for use according to any one of claims 23 to 26, wherein the cancer is selected from the group consisting of pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma, appendix cancer, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B - cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular carcinoma, breast cancer, ovarian cancer, prostate cancer, glioblastoma, renal cancer and sarcoma .

The pharmaceutical composition according to any one of claims 23 to 27, further comprising one or more pharma- ceutically acceptable excipients.