Tosylacetate based compounds and derivatives thereof as PHGDH inhibitors

A compound of formula (I), or a salt thereof,

• wherein
• n is 1 or 2;
• A1, A2, A3 and A4 are independently selected from —N═ and —CR13═ and wherein none, one or two independently selected A1, A2, A3 and A4 can be —N═;
• R13 is hydrogen, halogen, —C1-3alkyl, —O—C1-3alkyl;
• R1 is selected from the group consisting of hydrogen, —C1-3alkyl and —C1-3 alkyl-OH;
• R2 is
• wherein
• X is —N═ or —CR7—;
• R7 is selected from hydrogen, halogen, —C1-3alkyl and —O—C1-3 alkyl;
• R4 is selected from the group consisting of hydrogen, halogen, —C1-3haloalkyl, —C1-3alkyl;
• R5 is selected from the group consisting of hydrogen, halogen, —C1-3haloalkyl, —C1-3alkyl;
• or R4 and R5 taken together form a ring selected from a 5 or 6 membered heteroaryl, a 5 or 6 membered heterocyclyl and phenyl;
• E is selected from a bond, —C1-3alkylene-, —C1-3haloalkylene-, —C2-3alkynylene, 5 or 6 membered -heteroarylene- and 5 or 6 membered -heterocyclylene-;
• R6 is selected from hydrogen, halogen, —C1-3alkyl, which —C1-3alkyl is optionally substituted with one group selected from —NH2, —N(C1-3alkyl)2 and 5 or 6 membered heterocycloalkyl;
• or R2 is
• wherein
• R8 is selected from indolyl or phenyl, each of which group is optionally substituted with one, two or three substituents independently selected from halogen, —C1-3haloalkyl, —C1-3alkyl, —O—C1-3alkyl;
• R3 is
• and z is 1 or 2;
• or R3 is —C(R9R10)—COO—R11 and
• R9 and R10 are the same or different, independently selected from hydrogen, —C1-3alkyl, —C1-3alkyl-O—C1-3alkyl;
• or R9 and R10 taken together form a —C3-5cycloalkyl or a 6 membered heterocycloalkyl, which heterocycloalkyl is optionally substituted with —C(O)—C1-3alkyl;
• R11 is selected from the group consisting of hydrogen, —C3-6cycloalkyl, 4-6 membered heterocycloalkyl and —C1-5alkyl, which —C1-5alkyl group is optionally and independently substituted with one or two the same or different substituents, selected from R12;
• R12 is selected from the group consisting of —C3-6cycloalkyl, halogen, —OH, —O—C1-4alkyl, —O—C1-4alkyl-O—C1-4alkyl, —O—C1-4alkyl-OH, —OC(O)—C1-4alkyl, —NHCOO—C1-4alkyl, —SO2—C1-3alkyl, —N(C1-3alkyl)2, 5 or 6 membered heteroaryl and phenyl, which phenyl group is optionally substituted with —C1-3haloalkyl, or R12 is a 4 to 6 membered heterocycloalkyl, which heterocycloalkyl is optionally substituted with halogen or —C1-3alkyl.