6-6 fused bicyclic heteroaryl compounds and their use as LATS inhibitors

A compound of Formula II:

• or a pharmaceutically acceptable salt thereof
• wherein
• Ring A is
• (a) a 5- or 6-membered monocyclic heteroaryl that is linked to the remainder of the molecule through a carbon ring member and comprises, as ring member, 1 to 4 heteroatoms that are independently selected from the group consisting of N, O and S, provided that at least one of the heteroatom ring member is an unsubstituted nitrogen (—N═) positioned at the 3- or the 4-position relative to the linking carbon ring member of the 5-membered heteroaryl or at the para ring position of the 6-membered heteroaryl;
• or
• (b) a 9-membered fused bicyclic heteroaryl that is selected from the group consisting of:
• wherein “*” represents the point of attachment of ring A to the remainder of the molecule;
• and
• wherein ring A is unsubstituted or substituted by 1 to 2 substituents independently selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, —NH2, C1-6alkylamino, di-(C1-6alkyl)amino, C3-6cycloalkyl, and phenylsulfonyl;
• R0 is hydroxyl or C1-6alkoxy;
• R1 is hydrogen or C1-6alkyl;
• R2 is selected from the group consisting of
• (a) C1-8alkyl that is unsubstituted or substituted by 1 to 3 substituents independently selected from the group consisting of:
• (i) halogen;
• (ii) cyano;
• (iii) oxo;
• (iv) C2alkenyl;
• (v) C2alkynyl;
• (vi) C1-6haloalkyl;
• (vii) —OR6, wherein R6 is selected from hydrogen, C1-6alkyl that is unsubstituted or substituted by R0 or —C(O)R0;
• (viii) —NR7aR7b, wherein R7a is hydrogen or C1-6alkyl, and R7b is selected from hydrogen, —C(O)R0, C1-6alkyl that is unsubstituted or substituted by —C(O)R0;
• (ix) —C(O)R8, wherein R8 is R0 or —NH—C1-6alkyl-C(O)R0;
• (x) —S(O)2C1-6alkyl;
• (xi) monocyclic C3-6cycloalkyl or polycyclic C7-10cycloalkyl that are each unsubstituted or substituted by 1 to 2 substituents independently selected from the group consisting of halogen, C1-6alkyl, hydroxyC1-6alkyl, C1-6haloalkyl, R0, —NH2, C1-6alkylamino, and di-(C1-6alkyl)amino;
• (xii) 6-membered heterocycloalkyl comprising, as ring members, 1 to 2 heteroatoms independently selected from the group consisting of N, O and S and that is unsubstituted or substituted by 1 to 2 substituents independently selected from the group consisting of hydroxyl, halogen, C1-6alkyl, C1-6alkylamino, and di-(Ci-6alkyl)amino;
• (xiii) phenyl that is unsubstituted or substituted by halogen;
• (xiv) 5- or 6-membered monocyclic heteroaryl comprising, as ring members, 1 to 4 heteroatoms independently selected from the group consisting of N and O;
• and
• (xv) 9- or 10-membered fused bicyclic heteroaryl comprising, as ring member, 1 to 2 heteroatoms independently selected from the group consisting of N and O;
• (b) —S(O)2C1-6alkyl;
• (c) phenyl that is unsubstituted or substituted by 1 to 2 substituents independently selected from the group consisting of halogen, C1-6alkyl and R0;
• (d) C3-6cycloalkyl that is unsubstituted or substituted by 1 to 2 substituents independently selected from the group consisting of C1-6haloalkyl, R0, C1-6alkylamino, di-(C1-6alkyl)amino, —C(O)R0, and C1-6alkyl that is unsubstituted or substituted by R0 or —C(O)R0;
• and
• (e) 4-membered heterocycloalkyl comprising, as ring members, 1 to 2 heteroatoms selected from the group consisting of N, O and S and that is unsubstituted or substituted by 1 to 2 substituents independently selected from the group consisting of C1-6haloalkyl, R0, C1-6alkylamino, di-(C1-6alkyl)amino, —C(O)R0, and C1-6alkyl that is unsubstituted or substituted by R0 or —C(O)R0;
• or, R1 and R2 can be taken together with the nitrogen atom to which both are bound to form a 4- to 6-membered heterocycloalkyl that can include, as ring members, 1 to 2 additional heteroatoms independently selected from the group consisting of N, O, and S, wherein the 4- to 6-membered heterocycloalkyl formed by R1 and R2 taken together with the nitrogen atom to which both are bound is unsubstituted or substituted by 1 to 3 substituents independently selected from the group consisting of halogen, C1-6alkyl, C1-6haloalkyl, and R0;
• R3 is selected from the group consisting of hydrogen, halogen and C1-6alkyl;
• and
• R5 is selected from the group consisting of hydrogen, halogen and —NH-(3- to 8-membered heteroalkyl), wherein the 3- to 8-membered heteroC3-8alkyl of the —NH-(3- to 8-membered heteroalkyl) comprises 1 to 2 oxygen atoms as chain members and is unsubstituted or substituted by R0.