Heteroaryl derivatives as ddrs inhibitors

A method of treating a disease disorder or condition associated with dysregulation of DDR comprising administering to a subject in need thereof a compound of formula (I)

• wherein
• A is a ring selected from the group consisting of:
• wherein indicates a direct bond to NH;
• W1, W2 and W3 are substituents of ring A independently selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)halohydroxyalkyl, (C1-C4)alkoxy, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)haloalkoxy, (C1-C4)hydroxyalkyl, halogen, cyano, SF5, NR1R2-(C1-C4)alkyl, CONR1R2, NHCOR1, NR1R2, heterocycloalkyl, (C3-C7)cycloalkyl, (C1-C4)alkyl-heterocycloalkyl, (C1-C4)alkyl-heterocycloalkyl-(C1-C4)alkyl, (C1-C4)haloalkyl-cycloalkyl, (C1-C4)alkyl-(C3-C7)cycloalkyl, heterocycloalkyl-(C1-C4)alkyl, heterocycloalkyl-NH—(C1-C4)alkyl, (C3-C7)cycloalkyl-(C1-C4)alkyl, heterocycloalkyl-(C1-C4)alkoxy, (C1-C4)alkyl-CO-heterocycloalkyl-oxy, (C3-C7)cycloalkyl-(C1-C4)alkoxy, heterocycloalkyl-oxy, (C3-C7)cycloalkyl-oxy, (C1-C4)alkyl-heterocycloalkyl-carbonyl, monocyclic (C1-C4)alkyl-heteroaryl, (C1-C4)alkyl-sulfonyl, (C1-C4)haloalkyl-sulfonyl, (C1-C4)haloalkyl-sulfonylamino, (C1-C4)haloalkyl-sulfinyl, (C1-C4)haloalkyl-thio, (C1-C4)alkyl-thio-(C1-C4)alkyl, (C1-C4)alkyl-sulfonyl-(C1-C4)alkyl and (C1-C4)alkyl-sulfinyl-(C1-C4)alkyl;
• or, wherein W1 and W2 are in adjacent positions on ring A, W1 and W2 form a (C5-C6)cycloalkyl or a 5- or 6-membered heterocycloalkyl, wherein the (C5-C6)cycloalkyl or the 5- or 6-membered heterocycloalkyl are optionally substituted with 1 to 3 halogen atoms;
• L is selected from the group consisting of CO and CH2 or is absent;
• L1 is selected from the group consisting of NR, CH2 and O, wherein R is selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)hydroxyalkyl, (C1-C4)haloalkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C4)alkyl and deuterated (C1-C4)alkyl;
• RS is selected from the group consisting of hydrogen and methyl, when L1 is NR;
• RS is hydrogen, when L1 is CH2 or O;
• B is a mono- or bi-cyclic heteroaryl ring or bi-cyclic semisaturated heteroaryl ring;
• Y1 and Y2 are substituents of ring B independently selected from the group consisting of hydrogen, (C1-C4)alkyl, deuterated (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkoxy, (C1-C4)haloalkoxy, (C1-C4)hydroxyalkyl, halogen, cyano, SF5, (C1-C4) cyanoalkyl, (C1-C4)alkyl-sulfonyl, (C1-C4)haloalkyl-sulfonyl, CONR1R2, NHCOR1, NR1R2, NR1R2-(C1-C4)alkyl, heterocycloalkyl optionally substituted with 1 to 3 halogens, heterocycloalkyl-NH—(C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C4)alkyl-heterocycloalkyl, (C1-C4)alkyl-(C3-C7)cycloalkyl, heterocycloalkyl-(C1-C4)alkyl, (C3-C7)cycloalkyl-(C1-C4)alkyl, heterocycloalkyl-(C1-C4)alkoxy, (C3-C7)cycloalkyl-(C1-C4)alkoxy, heterocycloalkyl-oxy, (C3-C7)cycloalkyl-oxy, phenyl, (C1-C4)alkoxy substituted phenyl, (C1-C4)alkyl-thio-(C1-C4)alkyl, (C1-C4)alkyl-sulfonyl-(C1-C4)alkyl, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)haloalkyl-cycloalkyl, (C1-C4)alkyl-heterocycloalkyl-carbonyl and monocyclic heteroaryl, optionally substituted with 1 to 3 groups selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy and (C1-C4)alkoxy-(C1-C4)alkyl;
• R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)hydroxyalkyl, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)alkylamino-(C1-C4)alkyl, di-(C1-C4)alkylamino-(C1-C4)alkyl, optionally substituted (C3-C7)cycloalkyl, optionally substituted heterocycloalkyl and optionally substituted heterocycloalkyl-(C1-C4)alkoxy, wherein optional substituents are from 1 to 3 and are selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkyl, (C1-C4)haloalkoxy and carbamoyl;
• R3 is selected from the group consisting of (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkyl-phenyl and monocyclic heteroaryl;
• or a stereoisomer, tautomer, solvate or pharmaceutically acceptable salt thereof.

A compound of formula IV

• wherein
• A is a ring selected from the group consisting of:
• wherein indicates a direct bond to NH;
• W1, W2 and W3 are substituents of ring A independently selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)halohydroxyalkyl, (C1-C4)alkoxy, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)haloalkoxy, (C1-C4)hydroxyalkyl, halogen, cyano, SF5, NR1R2-(C1-C4)alkyl, CONR1R2, NHCOR1, NR1R2, heterocycloalkyl, (C3-C7)cycloalkyl, (C1-C4)alkyl-heterocycloalkyl, (C1-C4)alkyl-heterocycloalkyl-(C1-C4)alkyl, (C1-C4)haloalkyl-cycloalkyl, (C1-C4)alkyl-(C3-C7)cycloalkyl, heterocycloalkyl-(C1-C4)alkyl, heterocycloalkyl-NH—(C1-C4)alkyl, (C3-C7)cycloalkyl-(C1-C4)alkyl, heterocycloalkyl-(C1-C4)alkoxy, (C1-C4)alkyl-CO-heterocycloalkyl-oxy, (C3-C7)cycloalkyl-(C1-C4)alkoxy, heterocycloalkyl-oxy, (C3-C7)cycloalkyl-oxy, (C1-C4)alkyl-heterocycloalkyl-carbonyl, monocyclic (C1-C4)alkyl-heteroaryl, (C1-C4)alkyl-sulfonyl, (C1-C4)haloalkyl-sulfonyl, (C1-C4)haloalkyl-sulfonylamino, (C1-C4)haloalkyl-sulfinyl, (C1-C4)haloalkyl-thio, (C1-C4)alkyl-thio-(C1-C4)alkyl, (C1-C4)alkyl-sulfonyl-(C1-C4)alkyl and (C1-C4)alkyl-sulfinyl-(C1-C4)alkyl;
• or, wherein W1 and W2 are in adjacent positions on ring A, W1 and W2 form a (C5-C6)cycloalkyl or a 5- or 6-membered heterocycloalkyl, wherein the (C5-C6)cycloalkyl or the 5- or 6-membered heterocycloalkyl are optionally substituted with 1 to 3 halogen atoms;
• L1 is selected from the group consisting of NR, CH2 and O, wherein R is selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)hydroxyalkyl, (C1-C4)haloalkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C4)alkyl and deuterated (C1-C4)alkyl;
• Rs is selected from the group consisting of hydrogen and methyl when L1 is NR;
• RS is hydrogen when L1 is CH2 or O;
• R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C4)alkyl, (C1-C4)hydroxyalkyl, (C1-C4)alkoxy-(C1-C4)alkyl, (C1-C4)alkylamino-(C1-C4)alkyl, di-(C1-C4)alkylamino-(C1-C4)alkyl, optionally substituted (C3-C7)cycloalkyl, optionally substituted heterocycloalkyl and optionally substituted heterocycloalkyl-(C1-C4)alkoxy, wherein optional substituents are from 1 to 3 and are selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkyl, (C1-C4)haloalkoxy and carbamoyl;
• and
• R3 is selected from the group consisting of (C1-C4)alkyl, (C1-C4)haloalkyl, (C1-C4)alkyl-phenyl and monocyclic heteroaryl;
• or a stereoisomer, tautomer, solvate or pharmaceutically acceptable salt thereof;
• wherein the compound of formula IV is not 1-(3,5-dichlorophenyl)-3-(2-azaspiro[3.3]heptan-6-yl)urea;
• and wherein, when A ring is phenyl, L1 is NH and W1 and W2 are hydrogen, W3 is not para-OCF3.