Hpk1 inhibitors

A compound of formula

• or a tautomer or a stereoisomeric form thereof, wherein
• the dotted bond towards R1b is an optional bond that may be present when R1b and R4b are taken together to form a monocyclic or bicyclic aromatic heterocyclyl as defined herein;
• A1 represents CH or N;
• A2 represents CH;
• A3 represents CH or N;
• provided that only one of A1 and A3 represents N;
• A4 represents CH or N;
• A5 represents CR3a;
• A6 represents CH;
• R1a represents hydrogen;
• R1b represents hydrogen or CH3;
• R4a represents hydrogen, Ci-4alkyl, or C3-6cycloalkyl;
• R4b represents hydrogen, Ci-4alkyl, C3-6cycloalkyl, or
• a carbon linked monocyclic 4-, 5-, 6- or 7-membered non-aromatic heterocyclyl containing 1, 2 or 3 heteroatoms each independently selected from the group consisting of N, O, and S;
• wherein said S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• or
• R1b and R4b are taken together to form together with the atoms to which they are attached a monocyclic 5-membered aromatic heterocyclyl or a monocyclic 4-, 5-, 6- or 7-membered fully saturated heterocyclyl, each containing 1 N-atom and optionally 1 or 2 additional heteroatoms each independently selected from the group consisting of N, O, S;
• wherein said optional S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• or
• a bicyclic 6- to 12-membered aromatic or fully saturated heterocyclyl containing 1 N-atom and optionally 1 or 2 additional heteroatoms each independently selected from the group consisting of N, O, S;
• wherein said optional S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• wherein said monocyclic or bicyclic, aromatic or fully saturated heterocyclyl might be substituted on one or more of the carbon atoms with in total 1, 2 or 3 substituents each independently selected from the group consisting of —OH, CN, halo, R7, —O—R7, —S(═O)2—R7, —C(═O)—R7, —NR6cR6d, —C(═O)—NR6aR6b, and Hetc;
• wherein said monocyclic or bicyclic, aromatic or fully saturated heterocyclyl might be substituted on the optional additional nitrogen atoms with in total 1 or 2 substituents each independently selected from the group consisting of R7, —S(═O)2—R7, —C(═O)—R7, —C(═O)—NR6aR6b, and Hetd;
• provided that in case R1b and R4b are taken together, R4a represents hydrogen;
• and
• R1a represents hydrogen or R1a is absent when the dotted bond towards R1b is a bond;
• or
• R4a and R4b are taken together to form together with the N-atom to which they are attached a monocyclic 5-membered aromatic heterocyclyl or a monocyclic 4-, 5-, 6- or 7-membered fully saturated heterocyclyl, each containing 1 N-atom and optionally 1 or 2 additional heteroatoms each independently selected from the group consisting of N, O, S;
• wherein said optional S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• or
• a bicyclic 6- to 12-membered aromatic or fully saturated heterocyclyl containing 1 N-atom and optionally 1 or 2 additional heteroatoms each independently selected from the group consisting of N, O, S;
• wherein said optional S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• wherein said monocyclic or bicyclic, aromatic or fully saturated heterocyclyl might be substituted on one or more of the carbon atoms with in total 1, 2 or 3 substituents each independently selected from the group consisting of —OH, CN, halo, R7, —O—R7, —S(═O)2—R7, —C(═O)—R7, —NR6cR6d, —C(═O)—NR6aR6b, and Hetc;
• wherein said monocyclic or bicyclic, aromatic or fully saturated heterocyclyl might be substituted on the nitrogen atoms with in total 1 or 2 substituents each independently selected from the group consisting of R7, —S(═O)2—R7, —C(═O)—R7, —C(═O)—NR6aR6b, and Hetd;
• in case R4a and R4b are taken together, R1a represents hydrogen, and R1b represents hydrogen;
• R2 is selected from the group consisting of cyano;
• halo;
• —C(═O)—NR8aR8b, —CH2—NR8cR8d;
• Hetb;
• —P(═O)—(C1-4alkyl)2;
• —S(═O)2—C1-4alkyl;
• —S(═O)(═NRx)—C1-4alkyl;
• C1-6alkyl optionally substituted with 1 or 2 substituents each independently selected from the group consisting of halo, —OH, cyano, and —O—C1-4alkyl;
• C3-6cycloalkyl optionally substituted with 1 or 2 substituents each independently selected from the group consisting of halo, —OH, cyano and —O—C1-4alkyl;
• and
• C3-6cycloalkenyl optionally substituted with 1 or 2 substituents each independently selected from the group consisting of halo, —OH, cyano and —O—C1-4alkyl;
• R1a represents hydrogen, halo, R7, —O—R7, cyano, —C(═O)—NR6eR6f, Heta, or phenyl optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C1-4alkyl, —O—C1-4alkyl, C1-4alkyl substituted with one cyano, and C1-4alkyl substituted with 1, 2 or 3 halo atoms;
• Heta represents a carbon linked monocyclic 5-, 6- or 7-membered aromatic heterocyclyl or carbon linked monocyclic 4-, 5-, 6- or 7-membered non-aromatic heterocyclyl, each containing 1, 2 or 3 heteroatoms each independently selected from the group consisting of N, O or S;
• wherein said S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• or
• a carbon linked bicyclic 6- to 12-membered aromatic or non-aromatic heterocyclyl containing containing 1, 2 or 3 heteroatoms each independently selected from the group consisting of N, O or S;
• wherein said S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• wherein said monocyclic or bicyclic, aromatic or non-aromatic heterocyclyl might be substituted on one or more of the carbon atoms with in total 1, 2 or 3 substituents each independently selected from the group consisting of —OH, CN, halo, R7, —O—R7, —S(═O)2—R7, —C(═O)—R7, —NR6cR6d, —C(═O)—NR6aR6b, and Hetc;
• wherein said monocyclic or bicyclic, aromatic or non-aromatic heterocyclyl might be substituted on the nitrogen atoms with in total 1 or 2 substituents each independently selected from the group consisting of R7, —S(═O)2—R7, —C(═O)—R7, —C(═O)—NR6aR6b and Hetd;
• R6a, R6b, R6c, R6d, R6e, and R6f are each independently selected from the group consisting of hydrogen;
• C3-6cycloalkyl optionally substituted with one —OR5;
• and
• C1-4alkyl optionally substituted with one —OR5, wherein two hydrogen atoms on the same carbon atom of said C1-4alkyl might be taken together to form C3-6cycloalkyl;
• R5 represents hydrogen or C1-4alkyl;
• R8a, R8c, and R8d are each independently selected from the group consisting of hydrogen;
• C1-4alkyl optionally substituted with one —OH or —O—C1-4alkyl;
• and C3-6cycloalkyl optionally substituted with one —OH or —O—C1-4alkyl;
• R8b is selected from the group consisting C1-4alkyl optionally substituted with one —OH or —O—C1-4alkyl;
• and C3-6cycloalkyl optionally substituted with one —OH or —O—C1-4alkyl;
• or
• R8a and R8b, or R8c and R8d are taken together to form together with the N-atom to which they are attached a monocyclic fully saturated heterocyclyl containing 1 N-atom and optionally 1 or 2 additional heteroatoms each independently selected from the group consisting of N, O, S;
• wherein said optional S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• wherein said monocyclic 4-, 5-, 6- or 7-membered fully saturated heterocyclyl might be substituted on one or more of the carbon atoms with in total 1, 2 or 3 substituents each independently selected from the group consisting of —OH, CN, halo, R7, —O—R7, —S(═O)2—R7, —C(═O)—R7, —NR6cR6d, and —C(═O)—NR6aR6b;
• wherein said monocyclic fully saturated heterocyclyl might be substituted on the nitrogen atoms with in total 1 or 2 substituents each independently selected from the group consisting of R7, —S(═O)2—R7, —C(═O)—R7, and —C(═O)—NR6aR6d;
• each Hetc independently represents a monocyclic 4-, 5-, 6- or 7-membered fully saturated heterocyclyl containing 1, 2 or 3 heteroatoms each independently selected from the group consisting of N, O or S;
• wherein said S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• each Hetd independently represents a carbon linked monocyclic 4-, 5-, 6- or 7-membered fully saturated heterocyclyl containing 1, 2 or 3 heteroatoms each independently selected from the group consisting of N, O or S;
• wherein said S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• Hetb represents a monocyclic 4-, 5-, 6- or 7-membered non-aromatic heterocyclyl containing 1, 2 or 3 heteroatoms each independently selected from the group consisting of N, O, S;
• wherein said S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• or
• a bicyclic 6- to 12-membered non-aromatic heterocyclyl containing 1, 2 or 3 heteroatoms each independently selected from the group consisting of N, O, S;
• wherein said S-atom might be substituted to form S(═O), S(═O)2, or S(═O)(═NRx);
• wherein said monocyclic or bicyclic non-aromatic heterocyclyl might be substituted on one or more of the carbon atoms with in total 1, 2 or 3 substituents each independently selected from the group consisting of —OH, CN, halo, R7, —O—R7, —S(═O)2—R7, —C(═O)—R7, —NR6cR6d, and —C(═O)—NR6aR6b;
• wherein said monocyclic or bicyclic non-aromatic heterocyclyl might be substituted on the nitrogen atoms with in total 1 or 2 substituents each independently selected from the group consisting of R7, —S(═O)2—R7, —C(═O)—R7, and —C(═O)—NR6aR6b;
• each R7 independently represents C3-6cycloalkyl optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, —OH, —O—C1-4alkyl and cyano;
• or C1-4alkyl optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, —OH, —O—C1-4alkyl and cyano;
• each Rx independently represents hydrogen or C1-4alkyl or a pharmaceutically acceptable addition salt, an N-oxide, or a solvate thereof.