6-6 Fused Bicyclic Heteroaryl Compounds and their Use as LATS Inhibitors

Abstract

The present invention is related to 6-6 Fused Bicyclic Heteroaryl Compounds of the Formula A2 or A1 and their Use as LATS Inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; wherein the variables are as defined herein.The present invention further relates to a method of LATS inhibition in a cell population using a compound of Formula A1, or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, their use in the treatment and management of diseases or disorders.

1 - 315 . (canceled) 
     
     
         316 . A method comprising culturing a seeding population of cells in the presence of a composition comprising a LATS inhibitor, wherein the seeding population of cells comprises ocular cells, and wherein culturing the seeding population of cells generates an expanded population of cells. 
     
     
         317 . The method of  claim 316 , wherein the LATS inhibitor is a compound of Formula A1, or a salt, or stereoisomer thereof, 
       
         
           
           
               
               
           
         
         wherein 
         X 1  and X 2  are each independently CH or N; 
         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 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 
       
       
         
           
           
               
               
           
         
         wherein “*” represents the point of attachment of ring A to the remainder of the molecule; 
         wherein ring A is unsubstituted or substituted by 1 to 2 substituents independently selected from halogen, cyano, C 1-6 alkyl, C 1-6 haloalkyl, —NH 2 , C 1-6 alkylamino, di-(C 1-6 alkyl)amino, C 3-6 cycloalkyl, and phenylsulfonyl; 
         R 0  is hydroxyl or C 1-6 alkoxy; 
         R 1  is hydrogen or C 1-6 alkyl; 
         R 2  is selected from 
         (a) C 1-8 alkyl that is unsubstituted or substituted by 1 to 3 substituents independently selected from
 (i) halogen; 
 (ii) cyano; 
 (iii) oxo; 
 (iv) C 2 alkenyl; 
 (v) C 2 alkynyl; 
 (vi) C 1-6 haloalkyl; 
 (vii) —OR 6 , wherein R 6  is selected from hydrogen, C 1-6 alkyl that is unsubstituted or substituted by R 0  or —C(O)R 0 ; 
 (viii) —NR 7a R 7b , wherein R 7a  is hydrogen or C 1-6 alkyl, and R 7b  is selected from hydrogen, —C(O)R 0 , C 1-6 alkyl that is unsubstituted or substituted by —C(O)R 0 ; 
 (ix) —C(O)R 8 , wherein R 8  is R 0  or —NH—C 1-6 alkyl-C(O)R 0 ; 
 (x) —S(O) 2 C 1-6 alkyl; 
 (xi) monocyclic C 3-6 cycloalkyl or polycyclic C 7-10 cycloalkyl that are each unsubstituted or substituted by 1 to 2 substituents independently selected from halogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 haloalkyl, R 0 , —NH 2 , C 1-6 alkylamino, and di-(C 1-6 alkyl)amino; 
 (xii) 6-membered heterocycloalkyl comprising, as ring members, 1 to 2 heteroatoms independently selected from N, O and S and that is unsubstituted or substituted by 1 to 2 substituents independently selected from hydroxyl, halogen, C 1-6 alkyl, C 1-6 alkylamino, and di-(C 1-6 alkyl)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 N and O; and 
 (xv) 9- or 10-membered fused bicyclic heteroaryl comprising, as ring member, 1 to 2 heteroatoms independently selected from N and O; 
 
         (b) —S(O) 2 C 1-6 alkyl; 
         (c) phenyl that is unsubstituted or substituted by 1 to 2 substituents independently selected from halogen, C 1-6 alkyl and R 0 ; 
         (d) C 3-6 cycloalkyl that is unsubstituted or substituted by 1 to 2 substituents independently selected from C 1-6 haloalkyl, R 0 , C 1-6 alkylamino, di-(C 1-6 alkyl)amino, —C(O)R 0 , and C 1-6 alkyl that is unsubstituted or substituted by R 0  or —C(O)R 0 ; and 
         (e) 4-membered heterocycloalkyl comprising, as ring members, 1 to 2 heteroatoms selected from N, O and S and that is unsubstituted or substituted by 1 to 2 substituents independently selected from C 1-6 haloalkyl, R 0 , C 1-6 alkylamino, di-(C 1-6 alkyl)amino, —C(O)R 0 , and C 1-6 alkyl that is unsubstituted or substituted by R 0  or —C(O)R 0 ; 
         or R 1  and R 2  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 N, O, and S, wherein the 4-to 6-membered heterocycloalkyl formed by R 1  and R 2  taken together with the nitrogen atom to which both are bound is unsubstituted or substituted by 1 to 3 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, and R 0 ; 
         R 3  is selected from hydrogen, halogen and C 1-6 alkyl; and 
         R 5  is selected from hydrogen, halogen and —NH-(3- to 8-membered heteroalkyl), wherein the 3- to 8-membered heteroC 3-8 alkyl of the —NH-(3- to 8-membered heteroalkyl) comprises 1 to 2 oxygen atoms as chain members and is unsubstituted or substituted by R 0 . 
       
     
     
         318 . The method of  claim 317 , wherein the LATS inhibitor is a compound of a formula selected from Formulae I to IV: 
       
         
           
           
               
               
           
         
       
     
     
         319 . The method of  claim 318 , wherein ring A is: (a) selected from the group consisting of 
       
         
           
           
               
               
           
         
         which are each unsubstituted or substituted by a substituent selected from the group consisting of halogen, cyano, C 1-6 alkyl, C 1-6 haloalkyl, and —NH 2 ; or 
       
       (b) is 
       
         
           
           
               
               
           
         
          which is unsubstituted or substituted by C 1-6 alkyl. 
       
     
     
         320 . The method of  claim 318 , wherein ring A is 
       
         
           
           
               
               
           
         
       
     
     
         321 . The method of  claim 318 , wherein R 2  is selected from the group consisting of:
 (a) C 1-8 alkyl that is unsubstituted or substituted by A1 to A3 substituents independently selected from the group consisting of:
 (i) cyano; 
 (ii) C 2 alkynyl; 
 (iii) C 1-6 haloalkyl; 
 (iv) —OR 6 , wherein R 6  is selected from the group consisting of hydrogen, and C 1-6 alkyl that is unsubstituted or substituted by R 0  or —C(O)R 0 ; 
 (v) —NR 7a R 7b , wherein R 7a  is hydrogen or C 1-6 alkyl, and R 7b  is selected from the group consisting of hydrogen, —C(O)R 0 , and C 1-6 alkyl that is unsubstituted or substituted by —C(O)R 0 ; 
 (vi) —C(O)R 8 , wherein R 8  is R 0 ; 
 (vii) —S(O) 2 C 1-4 alkyl; 
 (viii) monocyclic C 3-6 cycloalkyl that is unsubstituted or substituted by a substituent selected from the group consisting of C 1-6 alkyl, hydroxyC 1-6 alkyl and R 0 ; 
 (ix) 6-membered heterocycloalkyl comprising, as ring members, 1 to 2 heteroatoms independently selected from the group consisting of N and O, and wherein the 6-membered heterocycloalkyl is unsubstituted or substituted by C 1-6 alkyl; 
 (x) phenyl that is unsubstituted or substituted by halogen; and 
   (b) C 3-6 cycloalkyl that is unsubstituted or substituted by 1 to 2 substituents independently selected from C 1-6 haloalkyl, R 0 , C 1-6 alkylamino, —C(O)R 0 , C 1-6 alkyl that is unsubstituted or substituted by —R 0  or —C(O)R 0 .   
     
     
         322 . The method of  claim 318 , wherein R 2  is selected from the group consisting of:
 n-propyl, isopropyl, t-butyl,   
       
         
           
           
               
               
           
         
       
     
     
         323 . The method of  claim 322 , wherein ring A is: (a) selected from the group consisting of 
       
         
           
           
               
               
           
         
         which are each unsubstituted or substituted by a substituent selected from the group consisting of halogen, cyano, C 1-6 alkyl, C 1-6 haloalkyl, and —NH 2 ; or 
         (b) is 
       
       
         
           
           
               
               
           
         
          which is unsubstituted or substituted by C 1-6 alkyl. 
       
     
     
         324 . The method of  claim 317 , wherein the LATS inhibitor is a compound of Formula II: 
       
         
           
           
               
               
           
         
       
     
     
         325 . The method of  claim 324 , wherein ring A is: (a) selected from the group consisting of 
       
         
           
           
               
               
           
         
         which are each unsubstituted or substituted by a substituent selected from the group consisting of halogen, cyano, C 1-6 alkyl, C 1-6 haloalkyl, and —NH 2 ; or 
         (b) is 
       
       
         
           
           
               
               
           
         
          which is unsubstituted or substituted by C 1-6 alkyl. 
       
     
     
         326 . The method of  claim 324 , wherein ring A is 
       
         
           
           
               
               
           
         
       
     
     
         327 . The method of  claim 324 , wherein R 2  is selected from the group consisting of:
 n-propyl, isopropyl, t-butyl,   
       
         
           
           
               
               
           
         
       
     
     
         328 . The method of  claim 327 , wherein ring A is: (a) selected from the group consisting of 
       
         
           
           
               
               
           
         
         which are each unsubstituted or substituted by a substituent selected from the group consisting of halogen, cyano, C 1-6 alkyl, C 1-6 haloalkyl, and —NH 2 ; or 
         (b) is 
       
       
         
           
           
               
               
           
         
          which is unsubstituted or substituted by C 1-6 alkyl. 
       
     
     
         329 . The method of  claim 327 , wherein ring A is 
       
         
           
           
               
               
           
         
       
     
     
         330 . The method of  claim 317 , wherein the LATS inhibitor of Formula A1 or salt thereof is selected from: N-(2-cyclopropylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N,N-diethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methoxy-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxy-2-methylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-butyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; N-ethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-cyclohexylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(3-methyloxetan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; N-butyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methyl-4-phenylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methanesulfonyl-2-methylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol; 3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)acetic acid; (1R,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; 4,4,4-trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-(1-methanesulfonyl-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (2S)-3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-[(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)amino]acetic acid; (2R)-3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; methyl 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoate; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-(2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethoxy)ethan-1-ol; 2-(hydroxymethyl)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol; 3-methyl-3-(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanamido)butanoic acid; 2-(pyridin-4-yl)-N-(1,1,1-trifluoro-3-phenylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-{[4-(dimethylamino)oxan-4-yl]methyl}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanoic acid; N-(2-methanesulfonylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(adamantan-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propanamide; 4,4,4-trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanoic acid; N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propane-2-sulfonamide; 2-(pyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4,4,4-trifluoro-2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; (1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentyl)methanol; N-(3-methoxycyclobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (1R,2R)-1-N,2-N-dimethyl-1-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]cyclohexane-1,2-diamine; methyl (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; ethyl 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylic acid; (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylic acid; 2-(pyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; N-(butan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylbut-3-yn-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (1r,3s)-3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutan-1-ol; 2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(pyridin-4-yl)-N-(2,4,4-trimethylpentan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(pentan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-methyl-1-(morpholin-4-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[1-(tert-butoxy)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4,4,4-trifluoro-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-pentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-[1-(1H-indol-3-yl)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[1-(4-fluorophenyl)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-phenylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(4-fluorophenyl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethan-1-ol; N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 1-({[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}methyl)cyclopentan-1-ol; N,N-dimethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-phenyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(3-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 6-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}hexanoic acid; N-(3-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanoic acid; N-(1-phenylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl N-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)carbamate; (1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; methyl 2-(1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)acetate; N-(2-methylpropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanenitrile; N-(6-aminohexyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-aminobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanenitrile; N-[2-methyl-1-(2-methylpiperidin-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine; N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-[4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl]pyridin-2-amine; 2-[1-(benzenesulfonyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-N-tert-butylpyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-methylpyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(2-methylbutan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl}amino)pentan-2-ol; N-ethyl-2-(3-fluoropyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-[2-methyl-2-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl}amino)propoxy]propan-2-ol; 2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1-methoxy-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; 2-(3-chloropyridin-4-yl)-N-cyclopentylpyrido[3,4-d]pyrimidin-4-amine; 1-(2-{[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2-methylpropoxy)-2-methylpropan-2-ol; N-methyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(4-methanesulfonyl-2-methylbutan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[3-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[2-chloro-5-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-(1 1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridin-2-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(1H-indazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3,5-dimethyl-1H-pyrazol-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1,1,1-trifluoro-2-methylpropan-2-yl)-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(4-hydroxy-2,4-dimethylpentan-2-yl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-(3,5-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2,3-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1,3-thiazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-[2-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-2-carbonitrile; N-(1-methylcyclopropyl)-2-(1,2-oxazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(dimethyl-1,2-oxazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H-pyrrolo[2,3-b]pyridin-4-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[3,2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclobutyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyrimidin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; N-propyl-2-{7H-pyrrolo[2,3-d]pyrimidin-5-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-cyclopropyl-1H-pyrazol-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-[(1R)-1-phenylethyl]-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(5-methyl-1H-pyrazol-4-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyridazin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1,3-oxazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H-pyrrolo[3,2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-1,2,3-triazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1,2-oxazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(2H-1,2,3,4-tetrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclobutyl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; 2-(1H-pyrazol-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; (1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)methanol; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-4-yl)-N-(2-methylpropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-amino-2-methylpropan-2-yl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 5-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-{[4-(tert-butylamino)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-5-yl]amino}ethoxy)ethan-1-ol; N-(4-methoxy-2-methylbutan-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[2-methyl-1-(propan-2-yloxy)propan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2S)-butan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2R)-butan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methoxy-2-methylpropan-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butan-1-ol; N-tert-butyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2,2-dimethyl-1-[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]piperidin-4-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}pentan-2-ol; N-cyclopentyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; dimethyl(3-methyl-3-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butyl)amine; N,N-diethyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}propoxy)propan-2-ol; N-propyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine; N-tert-butyl-2-{1H-pyrrolo[2,3-b]pyridin-4-yl}-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyridazin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyridin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine; N,N-diethyl-2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-amine; (3-{[2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-yl]amino}-3-methylbutyl)dimethylamine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)-1,7-naphthyridin-4-amine; 2-(3-fluoropyridin-4-yl)-4-(piperidin-1-yl)-1,7-naphthyridine; 2-(3-fluoropyridin-4-yl)-4-(morpholin-4-yl)-1,7-naphthyridine; N-tert-butyl-2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-amine; 2-(3-fluoropyridin-4-yl)-N-(2-methylbutan-2-yl)-1,7-naphthyridin-4-amine; 2-{[2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-yl]amino}-2-methylpropan-1-ol; 1-[2-(3-chloropyridin-4-yl)-1,7-naphthyridin-4-yl]-2,2-dimethylpiperidin-4-ol; 2-(3-fluoropyridin-4-yl)-N-[2-methyl-1-(morpholin-4-yl)propan-2-yl]-1,7-naphthyridin-4-amine; N-tert-butyl-2-(3-chloropyridin-4-yl)-1,7-naphthyridin-4-amine; N-((1R,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (S)—N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1 S,2R)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (R)—N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1 S,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1R,2R)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-(4-methylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 4-(piperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 4-(2-methylpiperidin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclobutyl)-1,7-naphthyridin-4-amine; 2-methyl-N1-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,2-diamine; N-(oxetan-3-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methylcyclopropyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 4-(3,3-dimethylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2,2-dimethyl-4-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)morpholine; N-(1-methylcyclobutyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2,2-dimethyl-N1-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,3-diamine; N 2 ,N 2 ,2-trimethyl-N 1 -(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,2-diamine; 4-(2-methylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2-methyl-N 1 -(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,3-diamine; (R)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)-1,7-naphthyridine; N-(tert-butyl)-N-methyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methylcyclobutyl)-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; N 1 ,N 1 ,3-trimethyl-N 3 -(2-(pyrimidin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl (2-methyl-1-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propan-2-yl)carbamate; tert-butyl (2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)ethyl)carbamate; 2-methyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine; N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)ethane-1,2-diamine; N,N,2-trimethyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; N 1 ,3-dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl (2,2-dimethyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propyl)carbamate; 2,2-dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butanamide; (R)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; 2,3-dimethyl-N 2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine; (S)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; ethyl 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanoate; N 1  N1,2,2-tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 4-(4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; N 2 ,N 2 ,2-trimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine; 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; (S)-1,1,1-trifluoro-2-methyl-3-((2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)amino)propan-2-ol; 2-(3-chloropyridin-4-yl)-N,N-diethyl-1,7-naphthyridin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl (3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butyl)carbamate; N 1 ,N 1 ,N 3 ,2,2-pentamethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; N 1 ,N 1 -diethyl-3-methyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; N 3 -(2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-aminopyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N,N 1 ,3-trimethylbutane-1,3-diamine; and 3-methyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine. 
     
     
         331 . The method of  claim 317 , wherein the LATS inhibitor or salt thereof is selected from: 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine. 
     
     
         332 . The method of  claim 317 , wherein the LATS inhibitor is N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine, or a salt thereof. 
     
     
         333 . The method of  claim 316 , wherein the ocular cells comprise corneal endothelial cells or limbal stem cells. 
     
     
         334 . The method of  claim 323 , wherein the ocular cells comprise corneal endothelial cells or limbal stem cells. 
     
     
         335 . The method of  claim 331 , wherein the ocular cells comprise corneal endothelial cells or limbal stem cells. 
     
     
         336 . The method of  claim 335 , wherein the seeding population of cells comprises greater than 20% corneal endothelial cells or greater than 20% limbal stem cells. 
     
     
         337 . The method of  claim 316 , wherein one or more of said cells comprises a non-naturally occurring insertion or deletion of one or more nucleic acid residues of a gene associated with facilitating a host vs graft immune response, wherein the insertion and/or deletion results in reduced or eliminated expression or function of said gene. 
     
     
         338 . The method of  claim 337 , wherein said gene is selected from: B2M, HLA-A, HLA-B and HLA-C. 
     
     
         339 . The method of  claim 337 , wherein the non-naturally occurring insertion and/or deletion has been introduced into the one or more cells with a gene editing system selected from: a CRISPR gene editing system, a TALEN gene editing system, a zinc finger nuclease gene editing system, a meganuclease gene editing system, AAV vector driven homologous recombination and lentiviral vectors-based genome editing technologies. 
     
     
         340 . The method of  claim 337 , wherein the gene editing system is a CRISPR gene editing system, and the gene is B2M. 
     
     
         341 . The method of  claim 340 , wherein the seeding cell population comprises at least 21% of B2M-negative cells. 
     
     
         342 . The method of  claim 323 , wherein one or more of said cells comprises a non-naturally occurring insertion and/or deletion of one or more nucleic acid residues of the B2M gene, wherein the insertion and/or deletion results in reduced or eliminated expression or function of said B2M gene, and wherein the non-naturally occurring insertion and/or deletion has been introduced into the one or more cells with a CRISPR gene editing system. 
     
     
         343 . The method of  claim 331 , wherein one or more of said cells comprises a non-naturally occurring insertion and/or deletion of one or more nucleic acid residues of the B2M gene, wherein the insertion and/or deletion results in reduced or eliminated expression or function of said B2M gene, and wherein the non-naturally occurring insertion and/or deletion has been introduced into the one or more cells with a CRISPR gene editing system. 
     
     
         344 . A cell population produced by the method of  claim 316 . 
     
     
         345 . A cell population produced by the method of  claim 323 . 
     
     
         346 . A cell population produced by the method of  claim 331 . 
     
     
         347 . A cell population produced by the method of  claim 343 . 
     
     
         348 . A pharmaceutical composition comprising the cell population of  claim 344  and at a pharmaceutically acceptable excipient. 
     
     
         349 . A pharmaceutical composition comprising the cell population of  claim 347  and at a pharmaceutically acceptable excipient.