Substituted amino-pyrimidine derivatives

Abstract

The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and/or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K/AKT/mTOR pathway. Advantageously, these compounds perform as dual PI3K/mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

What is claimed is: 
     
         1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkylamino, optionally substituted dialkylamino, optionally substituted arylamino, optionally substituted heteroarylamino, optionally substituted heterocycleamino, optionally substituted alkylcarbonylamino, optionally substituted alkylsulfonylamino, optionally substituted alkylthio, optionally substituted alkylsulfonyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycleoxy, optionally substituted alkylaminocarbonyl, optionally substituted arylaminocarbonyl, optionally substituted heteroarylaminocarbonyl, or optionally substituted heterocycleaminocarbonyl; 
         R 2  is optionally substituted morpholine or thiomorpholine; 
         R 3  is H, F, Cl, CH 3 , or CH 3 O; 
         X is CH or N; 
         or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
       
     
     
         2 . The compound according to  claim 1 , wherein R 2  is morpholine. 
     
     
         3 . The compound according to  claim 1 , wherein R 1  is a substituted phenyl of the structure: 
       
         
           
           
               
               
           
         
         wherein:
 n is 1 to 5; 
 
         each R 8  is independently selected from the group consisting of halogen, alkyl, aryl, alkylsulfonyl, alkylthio, alkylcarbonylamino, halogenated alkylcarbonylamino, alkylsulfonylamino, arylsulfonylamino, alkylaminocarbonyl, alkylaminocarbonylamino, alkylaminoalkylcarbonylamino, hydroxyalkylcarbonylamino, heteroarylcarbonylamino, heteroarylalkylcarbonylamino, heteroarylcarbonyl, heterocyclecarbonylamino, arylcarbonylamino, alkylsulfonylheterocyclecarbonyl, heterocyclecarbonyl, heterocycleaminocarbonyl, heteroarylalkylamino, hydroxyalkylamino, heterocyclealkylcarbonylamino, or cyanoalkylcarbonylamino. 
       
     
     
         4 . The compound according to  claim 1 , wherein R 1  is a heteroaryl of the formula: 
       
         
           
           
               
               
           
         
         wherein:
 Z 1  is O, S, or NR 5 ; 
 Z 2  is CR 4  or N; 
 
         R 4 H, alkyl,  C(O)(optionally substituted heterocycle), or  C(O)NH(optionally substituted heteroaryl); 
         R 5  is absent, H or alkyl; and
 p is 0 to 2. 
 
       
     
     
         5 . The compound according to  claim 1 , wherein R 1  is a heteroaryl selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein:
 m is 0 to 4; 
 
         q is 0 to 3; 
         each R 6  is, independently, selected from the group consisting of halogen, piperidinyl, 4-CH 3 -piperidinyl, alkylsulfonyl, aminosulfonylalkyl, and alkylcarbonylamino. 
       
     
     
         6 . The compound according to  claim 1 , wherein R 1  is an optionally substituted benzo[b]oxazine. 
     
     
         7 . The compound according to  claim 1 , wherein R 1  is optionally substituted alkyl. 
     
     
         8 . The compound according to  claim 7 , wherein R 1  is: 
       
         
           
           
               
               
           
         
         wherein:
 Y and Y′ are, independently, N or CH; and 
 R 7  is H,  C(O)(hydroxyalkyl),  C(O)(alkyl), or  NHC(O)(alkyl). 
 
       
     
     
         9 . The compound according to  claim 1 , which is of formulae (II), (III), or (IV): 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound according to  claim 1  which is selected from the group consisting of:
 5-(7-(3 (methylsulfonyl)phenyl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine; 
 5-(6-fluoro-7-(3-(methylsulfonyl)phenyl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-acetamide; 
 4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-cyclopropylbenzamide; 
 (5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)furan-2-yl)(4-methylpiperazin-1-yl)methanone; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-hydroxy-2-methylpropanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanecarboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-fluorobenzenesulfonamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-(4-hydroxypiperidin-1-yl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)morpholine-4-carboxamide; 
 1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one; 
 5-(4-morpholino-7-(pyrimidin-5-yl)quinazolin-2-yl)pyrimidin-2-amine; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)acetamide; 
 5-(7-(1-methyl-1H-pyrazol-4-yl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine; 
 1-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-3-methylurea; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)methanesulfonamide; 
 5-(4-morpholino-7-(thiophen-3-yl)quinazolin-2-yl)pyrimidin-2-amine; 
 5-(7-(5-(methylsulfonyl)pyridin-3-yl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine; 
 5-(7-(2-fluoropyridin-3-yl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-amine; 
 5-(7-(3-(methylsulfonyl)phenyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)methanesulfonamide; 
 5-(7-(1-methyl-1H-pyrazol-4-yl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine; 
 5-(4-morpholino-7-(pyrimidin-5-yl)pyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine; 
 5-(7-(2-fluoropyridin-3-yl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine; 
 5-(7-(furan-2-yl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine 
 5-(7-(5-methylfuran-2-yl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-N-methylacetamide; 
 1-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methylurea; 
 1-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methylurea; 
 N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)pyridin-3-yl)acetamide; 
 N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)pyridin-3-yl)cyclopropanecarboxamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-3-fluorophenyl)cyclopropanecarboxamide; 
 4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-methylbenzamide; 
 5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(pyridin-3-yl)furan-2-carboxamide; 
 1-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)benzoyl)-piperazin-1-yl)ethanone; 
 (3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-(methyl-sulfonyl)piperazin-1-yl)methanone; 
 4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(thiazol-2-yl)-benzamide; 
 4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(pyridin-4-yl)-benzamide; 
 (4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-hydroxypiperidin-1-yl)methanone; 
 (3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-hydroxypiperidin-1-yl)methanone; 
 3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N,N-dimethylbenzamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-(dimethylamino)-acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-hydroxypropanamide; 
 (S)—N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-2-hydroxypropanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxypropanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-(dimethylamino)acetamide; 
 (S)—N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxypropanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxy-2-methylpropanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-cyano-2-methylpropanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-hydroxyacetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-fluoropropanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-cyanoacetamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-methylphenyl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopentanecarboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)nicotinamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-5-methylfuran-2-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclohexanecarboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-1-cyanocyclopropanecarboxamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanecarboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)tetrahydro-2H-pyran-4-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)pyrazine-2-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)adamantane-1-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-methylpentanamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)furan-2-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-(trifluoromethyl)nicotinamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-1,2,3-thiadiazole-4-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-hydroxycyclohexanecarboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluoro-phenyl)nicotinamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)-5-methylfuran-2-carboxamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-5-methylfuran-2-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-fluorobenzamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methyl-1H-pyrazole-5-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclobutanecarboxamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)nicotinamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclobutanecarboxamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)furan-2-carboxamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-3-methyl-1H-pyrazole-5-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanesulfonamide; 
 N-(4-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)cyclopropanesulfonamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-(4-methylpiperazin-1-yl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-2-morpholinoacetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)-2-(4-methylpiperazin-1-yl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)-2-(4-methylpiperazin-1-yl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)-4-methylpiperazine-1-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)phenyl)morpholine-4-carboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-4-methylpiperazine-1-carboxamide; 
 1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one; 
 1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperazin-1-yl)-2-hydroxy-2-methylpropan-1-one; 
 1-(4-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperazin-1-yl)-ethanone; 
 N-(1-((2-(2-aminopyrimidin-5-yl)-4-morpholinoquinazolin-7-yl)methyl)piperidin-4-yl)-acetamide; 
 5-(4-morpholino-7-(piperazin-1-ylmethyl)pyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)cyclopropanecarboxamide; 
 N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)pyridin-3-yl)-methanesulfonamide; 
 3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(3-fluoropyridin-4-yl)benzamide; 
 3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-cyclopropylbenzamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)-5-fluoronicotinamide; 
 5-(7-(5-(4-methylpiperazin-1-yl)pyridin-3-yl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)-pyrimidin-2-amine; 
 5-(7-(3-(4-methylpiperazin-1-yl)phenyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)-pyrimidin-2-amine; 
 3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-(2-(dimethylamino)ethyl)benzamide; 
 3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-methylbenzamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)propionamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)isobutyramide; 
 5-(4-morpholino-7-(3-(piperazin-1-yl)phenyl)pyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine; 
 3-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)piperazin-1-yl)-2,2-dimethyl-3-oxopropanenitrile; 
 1-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)piperazin-1-yl)-2-hydroxy-2-methylpropan-1-one; 
 2-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)propan-2-ol; 
 (3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-methylpiperazin-1-yl)methanone; 
 6-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 
 1-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)piperazin-1-yl)-2-(dimethylamino)ethanone; 
 2-(4-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)piperazin-1-yl)ethanol; 
 N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-(4-methylpiperazin-1-yl)phenyl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)-cyclopropanecarboxamide; 
 (3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)phenyl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone; 
 N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-(4-methylpiperazin-1-yl)phenyl)cyclopropanecarboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)pivalamide; 
 N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2,4-difluorophenyl)acetamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-4-fluorophenyl)-1-cyanocyclopropanecarboxamide; 
 N-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)-1-cyanocyclopropanecarboxamide; and 
 N-(5-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-2-fluorophenyl)-cyclopropanecarboxamide. 
 
     
     
         11 . The compound according to  claim 1  which is a prodrug of formula (I). 
     
     
         12 . The compound according to  claim 11 , wherein the prodrug is a diester. 
     
     
         13 . The compound according to  claim 12 , wherein the diester is  C(O))(C 1  to C 6  alkyl)OC(O)(C 1  to C 1  alkyl). 
     
     
         14 . The compound according to  claim 1 , which is selected from the group consisting of:
 1-((acetyl(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)carbamoyl)oxy)ethyl acetate;   ((acetyl(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)carbamoyl)oxy)methyl acetate; and   (((3-(2-(2-aminopyrimidin-5-yl)-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)(cyclopropanecarbonyl)carbamoyl)oxy)methyl acetate.   
     
     
         15 . A method for co-regulating PI3K and mTOR, said method comprising administering a therapeutically effective amount of a compound of  claim 1  to a patient in need thereof. 
     
     
         16 . A method for treating a condition treatable by inhibiting the PI3K/AKT/pathway, said method comprising administering a therapeutically effective amount of a compound of  claim 1  to a patient in need thereof. 
     
     
         17 . A method for treating a disease characterized by an abnormal cellular proliferation resulting from a dysregulated PI3K/AKT/mTOR pathway, said method comprising administering of a therapeutically effective amount of a compound of  claim 1  to a patient in need thereof. 
     
     
         18 . The method according to  claim 17 , wherein said disease is cancer. 
     
     
         19 . The method according to  claim 17 , wherein said condition is an inflammatory disorder. 
     
     
         20 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier.