Tricyclic pyrimidines as cyclin-dependent kinase 7 (CDK7) inhibitors

A compound of formula (I), including any tautomeric and stereochemically isomeric form, isotopically labeled derivative, or a pharmaceutically acceptable salt or solvate thereof:

• wherein,
• X is a 4-7 membered non-aromatic heterocycle, a 4-10 membered non-aromatic bridged heterocycle, C3-7cycloalkyl, C5-7cycloalkenyl;
• wherein each of the cycles, independently, may be optionally substituted with —C1-3alkyl;
• R1 is a 4-7 membered non-aromatic heterocycle having at least one nitrogen atom, wherein the at least one nitrogen atom is substituted with —C(═O)—CH═CH—R6, or —C(═O)—CH≡CH—R7, and wherein the 4-7 membered non-aromatic heterocycle is optionally substituted with C1-3alkyl, halo, or D;
• or R1 is C1-3alkyl substituted with —NH—C(═O)—CH═CH—R6 or —NH—C(═O)—CH═CH—R7;
• A is a CR2 or N;
• R2 is H, C1-3alkyl, cyano, halo, or C2-3alkynyl;
• R3 is C1-3alkyl, H, halogen, C2-3alkenyl, C2-3alkynyl, cyano, C3-7cycloalkyl;
• C1-3alkyl substituted with one, two, or three halo, hydroxy, carboxyl, amino, mono- or di(C1-6alkyl)amino;
• 1-imidazolyl, 2-imidazolyl, or 4-imidazolyl;
• R4 is C1-3alkyl;
• C1-3alkyl substituted with one, two, or three halo;
• H;
• R5 is a 4-7 membered saturated or partially unsaturated heterocycle, a 5-6 membered heteroaryl, or a 6-12 membered spiro-bicyclic heterocycle;
• wherein each of the cycles have one, two, or three heteroatoms selected from sulphur, nitrogen, and oxygen;
• and wherein,
• said sulphur, if present, is substituted with dioxo, or with oxo and imino;
• said one, two, or three nitrogens, if present, may, each independently, be optionally substituted with C1-3alkyl;
• any one of the carbon atoms of the cycles may be optionally substituted with C1-3alkyl, hydroxyC1-3alkyl, C1-3alkoxy, oxo, C1-3alkylsulfonyl, cyano, hydroxy, halo, carboxyl, mono- or di(C1-6alkyl)amino, polyhaloC1-3alkyl, polyhaloC1-3alkoxy, C2-3alkenyl, and C2-3alkynyl;
• R6 is H;
• —C1-3alkyl optionally substituted with one, two, or three substituents selected from halo, D, and —NR7aR7b, wherein each of R7a and R7b is, independently, C1-3alkyl;
• or R7a and R7b taken together form a heterocycle;
• and
• R7 is —C1-3alkyl optionally substituted with one, two, or three substituents selected from halo, D, and —NR7aR7b, wherein each of R7a and R7b is, independently, C1-3alkyl, or R7a and R7b taken together form a heterocycle.