Pyrimidine derivatives as mtor inhibitors

Abstract

The invention relates to compounds of formula (I) wherein X, R 1 , R 2 , T, m, n, o have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

We claim: 
     
         1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, prodrug or metabolite thereof, wherein 
         X is O; or S; 
         m is 1; 2; or 3; 
         n is 1; 2; or 3; 
         R 1  is H; C(O)R 3 ; C(O)OR 3 ; C(O)N(R 3 R 3a ); S(O) 2 N(R 3 R 3a ); S(O)N(R 3 R 3a ); S(O) 2 R 3 ; S(O)R 3 ; T 1 ; or C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more R 4 , which are the same or different; 
         R 3 , R 3a  are independently selected from the group consisting of H; T 1 ; and C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more R 4 , which are the same or different; 
         R 4  is halogen; CN; C(O)OR 5 ; OR 5 ; C(O)R 5 ; C(O)N(R 5 R 5a ); S(O) 2 N(R 5 R 5a ); S(O)N(R 5 R 5a ); S(O) 2 R 5 ; S(O)R 5 ; N(R 5 )S(O) 2 N(R 5 R 5b ); N(R 5 )S(O)N(R 5a R 5b ); SR 5 ; N(R 5 R 5a ); NO 2 ; OC(O)R 5 ; N(R 5 )C(O)R 5a ; N(R 5 )S(O) 2 R 5a ; N(R 5 )S(O)R 5a ; N(R 5 )C(O)N(R 5a R 5b ); N(R 5 )C(O)OR 5a ; OC(O)N(R 5 R 5a ); or T 1 ; 
         R 5 , R 5a , R 5b  are independently selected from the group consisting of H; and C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more halogen, which are the same or different; 
         T 1  is C 3-7 cycloalkyl; 4 to 7 membered heterocyclyl; 8 to 11 membered heterobicyclyl; phenyl; naphthyl; indenyl; or indanyl, wherein T 1  is optionally substituted with one or more R 6 , which are the same or different; 
         R 6  is halogen; CN; C(O)OR 7 ; OR 7 ; oxo (═O), where the ring is at least partially saturated; C(O)R 7 ; C(O)N(R 7 R 7a ); S(O) 2 N(R 7 R 7a ); S(O)N(R 7 R 7a ); S(O) 2 R 7 ; S(O)R 7 ; N(R 7 )S(O) 2 N(R 7a R 7b ); N(R 7 )S(O)N(R 7a R 7b ); SR 7 ; N(R 7 R 7a ); NO 2 ; OC(O)R 7 ; N(R 7 )C(O)R 7a ; N(R 7 )S(O) 2 R 7a ; N(R 7 )S(O)R 7a ; N(R 7 )C(O)N(R 7a R 7b ); N(R 7 )C(O)OR 7a  OC(O)N(R 7 R 7a ); or C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more R 8 , which are the same or different; 
         R 7 , R 7a , R 7b  are independently selected from the group consisting of H; C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more halogen, which are the same or different; 
         R 8  is halogen; CN; C(O)OR 9 ; OR 9 ; C(O)R 9 ; C(O)N(R 9 R 9a ); S(O) 2 N(R 9 R 9a ); S(O)N(R 9 R 9a ); S(O) 2 R 9 ; S(O)R 9 ; N(R 9 )S(O) 2 N(R 9a R 9b ); N(R 9 )S(O)N(R 9a R 9b ); SR 9 ; N(R 9 R 9a ); NO 2 ; OC(O)R 9 ; N(R 9 )C(O)R 9a ; N(R 9 )S(O) 2 R 9a ; N(R 9 )S(O)R 9a ; N(R 9 )C(O)N(R 9a R 9b ); N(R 9 )C(O)OR 9a ; or OC(O)N(R 9 R 9a ); 
         R 9 , R 9a , R 9b  are independently selected from the group consisting of H; and C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more halogen, which are the same or different; 
         o is 1; 2; 3; or 4; 
         Each R 2  is independently selected from the group consisting of H; halogen; CN; C(O)OR 10 ; OR 10a ; oxo (═O); C(O)R 10 ; C(O)N(R 10 R 10a ); S(O) 2 N(R 10 R 10a ); S(O)N(R 10 R 10a ); S(O) 2 R 10 ; S(O)R 10 ; N(R 10 )S(O) 2 N(R 10a R 10b ); N(R 10 )S(O)N(R 10a R 10b ); SR 10 ; N(R 10 R 10a ); NO 2 ; OC(O)R 10 ; N(R 10 )C(O)R 10a ; N(R 10 )S(O) 2 R 10a ; N(R 10 )S(O)R 10a ; N(R 10 )C(O)N(R 10a R 10b ); N(R 10 )C(O)OR 10a ; OC(O)N(R 10 R 10a ); and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more R 11 , which are the same or different; 
         R 10 , R 10a , R 10b  are independently selected from the group consisting of H; C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; 
         R 11  is halogen; CN; C(O)OR 12 ; OR 12 ; C(O)R 12 ; C(O)N(R 12 R 12a ); S(O) 2 N(R 12 R 12a ); S(O)N(R 12 R 12a ); S(O) 2 R 12 ; S(O)R 12 ; N(R 12 )S(O) 2 N(R 12a R 12b ); N(R 12 )S(O)N(R 12a R 12b ); SR 12 ; N(R 12 R 12a ); NO 2 ; OC(O)R 12 ; N(R 12 )C(O)R 12a ; N(R 12 )S(O) 2 R 12a ; N(R 12 )S(O)R 12a ; N(R 12 )C(O)N(R 12a R 12b ); N(R 12 )C(O)OR 12a ; or OC(O)N(R 12 R 12a ); 
         R 12 , R 12a , R 12b  are independently selected from the group consisting of H; and C 1-6  alkyl, wherein C 1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; 
         T is phenyl; or 5 to 6 membered aromatic heterocycle, wherein T is substituted with N(R 13a )C(O)N(R 13b R 13 ) and optionally further substituted with one or more R 14 , which are the same or different; 
         R 14  is halogen; CN; C(O)OR 15 ; OR 15 ; C(O)R 15 ; C(O)N(R 15 R 15a ); S(O) 2 N(R 15 R 15a ); S(O)N(R 15 R 15a ); S(O) 2 R 15 ; S(O)R 15 ; N(R 15 )S(O) 2 N(R 15a R 15b ); N(R 15 )S(O)N(R 15a R 15b ); SR 15 ; N(R 15 R 15a ); NO 2 ; OC(O)R 15 ; N(R 15 )C(O)R 15a ; N(R 15 )S(O) 2 R 15a ; N(R 15 )S(O)R 15a ; N(R 15 )C(O)N(R 15 R 15b ); N(R 15 )C(O)OR 15a ; OC(O)N(R 15 R 15a ); or C 1-6  alkyl, wherein C 1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; 
         R 13a , R 13b , R 15 , R 15a , R 15b  are independently selected from the group consisting of H; C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; 
         R 13  is H; T 2 ; and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more R 16 , which are the same or different; 
         R 16  is halogen; CN; C(O)OR 17 ; OR 17 ; C(O)R 17 ; C(O)N(R 17 R 17a ); S(O) 2 N(R 17 R 17a ); S(O)N(R 17 R 17a ); S(O) 2 R 17 ; S(O)R 17 ; N(R 17 )S(O) 2 N(R 17a R 17b ); N(R 17 )S(O)N(R 17a R 17b ); SR 7 ; N(R 17 R 17a ); NO 2 ; OC(O)R 17 ; N(R 17 )C(O)R 17a ; N(R 17 )S(O) 2 R 17a ; N(R 17 )S(O)R 17a ; N(R 17 )C(O)N(R 17a R 17b ); N(R 17 )C(O)OR 17a ; OC(O)N(R 17 R 17a ); or T 2 ; 
         R 17 , R 17a , R 17b  are independently selected from the group consisting of H; and C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more halogen, which are the same or different; 
         Optionally R 13 , R 13b  are joined together with the nitrogen atom to which they are attached to form an at least the nitrogen atom as ring heteroatom containing 4 to 7 membered heterocyclyl ring; or 8 to 11 membered heterobicyclyl ring, wherein the 4 to 7 membered heterocyclyl ring; and the 8 to 11 membered heterobicyclyl ring are optionally substituted with one or more R 18 , which are the same or different; 
         T 2  is C 3-7 cycloalkyl; 4 to 7 membered heterocyclyl; 8 to 11 membered heterobicyclyl; phenyl; naphthyl; indenyl; or indanyl, wherein T 2  is optionally substituted with one or more R 18 , which are the same or different; 
         R 18  is halogen; CN; C(O)OR 19 ; OR 19 ; Oxo (═O), where the ring is at least partially saturated; C(O)R 19 ; C(O)N(R 19 R 19a ); S(O) 2 N(R 19 R 19a ); S(O)N(R 19 R 19a ); S(O) 2 R 19 ; S(O)R 19 ; N(R 19 )S(O) 2 N(R 19a R 19b ); N(R 19 )S(O)N(R 19a R 19b ); SR 19 ; N(R 19 R 19a ); NO 2 ; OC(O)R 19 ; N(R 19 )C(O)R 19a ; N(R 19 )S(O) 2 R 19a ; N(R 19 )S(O)R 19a ; N(R 19 )C(O)N(R 19a R 19b ); N(R 19 )C(O)OR 19a ; OC(O)N(R 19 R 19a ); or C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more R 20 , which are the same or different; 
         R 19 , R 19a , R 19b  are independently selected from the group consisting of H; C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more halogen, which are the same or different; 
         R 20  is halogen; CN; C(O)OR 21 ; OR 21 ; C(O)R 21 ; C(O)N(R 21 R 21a ); S(O) 2 N(R 21 R 21a ); S(O)N(R 21 R 21a ); S(O) 2 R 21 ; S(O)R 21 ; N(R 21 )S(O) 2 N(R 21a R 21b ); N(R 21 )S(O)N(R 21a R 21b ); SR 21 ; N(R 21 R 21a ); NO 2 ; OC(O)R 21 ; N(R 21 )C(O)R 21a ; N(R 21 )S(O) 2 R 21a ; N(R 21 )S(O)R 21a ; N(R 21 )C(O)N(R 21a R 21b ); N(R 21 )C(O)OR 21a ; or OC(O)N(R 21 R 21a ); 
         R 21 , R 21a , R 21b  are independently selected from the group consisting of H; and C 1-6  alkyl, wherein C 1-6  alkyl is optionally substituted with one or more halogen, which are the same or different. 
       
     
     
         2 . A compound of  claim 1 , wherein X is O. 
     
     
         3 . A compound of  claim 1 , wherein m and n are independently 1 or 2. 
     
     
         4 . A compound of  claim 1 , wherein m+n=2 or 3. 
     
     
         5 . A compound of  claim 1 , wherein o is 1 or 2. 
     
     
         6 . A compound of  claim 1 , wherein T is phenyl; pyridine; pyrimidine; pyridazine; or pyrazine and wherein T is substituted with N(R 13a )C(O)N(R 13b R 13 ) and optionally further substituted with one or more R 14 , which are the same or different. 
     
     
         7 . A compound of  claim 1 , wherein T is only substituted with N(R 13a )C(O)N(R 13b R 13 ). 
     
     
         8 . A compound of  claim 1 , wherein X, m, n, o, T are selected to give formula (Ia), (Ib) or (Ic) 
       
         
           
           
               
               
           
         
         wherein p is 0, 1, or 2. 
       
     
     
         9 . A compound of  claim 1 , wherein X, m, n, o, T, R 14  are selected to give formula (Id), (Ie) or (If) 
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound of  claim 1 , wherein R 1  is H; C(O)R 3 ; S(O) 2 R 3 ; optionally substituted C 1-6  alkyl; C(O)OR 3 ; C(O)NHR 3 ; optionally substituted T 1 ; or optionally substituted CH 2 -T 1 . 
     
     
         11 . A compound of  claim 1 , wherein R 3  is H; optionally substituted C 1-6  alkyl; optionally substituted T 1 ; or optionally substituted CH 2 -T 1 . 
     
     
         12 . A compound of  claim 1 , wherein T 1  is phenyl; or C 3-7 cycloalkyl and wherein T 1  is optionally substituted with one or more R 6 , which are the same or different. 
     
     
         13 . A compound of  claim 1 , wherein R 2  is methyl. 
     
     
         14 . A compound of  claim 1 , wherein R 13  is H; optionally substituted C 1-6  alkyl; or optionally substituted T 2 . 
     
     
         15 . A compound of  claim 1  selected from the group consisting of:
 (S)-1-(4-(6-formyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-methyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(6-formyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-1-ethyl-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (R)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-tert-butyl-2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate; 
 (S)-1-methyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-methyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-tert-butyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-ethyl-3-(4-(6-(4-fluorobenzyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 1-ethyl-3-(4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(6-(4-fluorobenzoyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(7-ethyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(7-(4-fluorobenzyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(7-(4-fluorobenzoyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-cyclopropylurea; 
 (S)-1-ethyl-3-(4-(6-isobutyryl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6-pivaloyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-1-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-2-(4-(3-cyclopropylureido)phenyl)-N-ethyl-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxamide; 
 (S)-ethyl 2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-(4-(6-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-cyclopropylurea; 
 (S)-1-cyclopropyl-3-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-neopentyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(7-methyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(6-ethyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(7-(cyclopropylmethyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-1-cyclopropyl-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(6-ethyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(7-(cyclopropylmethyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-7-neopentyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(7-isobutyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(7-isopropyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(6-isobutyryl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-pivaloyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-methylurea; 
 (S)-1-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-propylurea; 
 (S)-1-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-isopropylurea; 
 (S)-1-(3-hydroxypropyl)-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-fluorophenyl)-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(3-methoxypropyl)-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(2-(dimethylamino)ethyl)-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclobutyl-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(7-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-1-ethyl-3-(4-(7-isobutyryl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-7-pivaloyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(7-acetyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-1-(4-(7-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-cyclopropylurea; 
 (S)-1-cyclopropyl-3-(4-(7-isobutyryl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(7-acetyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-cyclopropylurea; 
 tert-butyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-7-pivaloyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(6-isobutyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(6-isobutyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6-neopentyl-6,7-dihydro-5H-pyrrol[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6-(2,2,2-trifluoroethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 1-ethyl-3-(4-(6-methyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 ethyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(5-methylisoxazol-3-yl)urea; 
 (S)-1-(2-hydroxyethyl)-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(7-isopropyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(7-isobutyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-ethyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate; 
 (S)-ethyl 2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate; 
 N-ethyl-2-(4-(3-ethylureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxamide; 
 (S)-1-(6-hydroxypyridin-2-yl)-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-methyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate; 
 1-ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-methyl 2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate; 
 (S)-1-(1-methyl-1H-pyrazol-4-yl)-3-(4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(2-fluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-methyl 2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)—N-ethyl-2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide; 
 (S)-2-(4-(3-cyclopropylureido)phenyl)-N-ethyl-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide; 
 (S)-methyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-7-(2-(pyridin-3-yl)acetyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-(3-(dimethylamino)propanoyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 1-ethyl-3-(4-(7-methyl-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 N-ethyl-2-(4-(3-ethylureido)phenyl)-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide; 
 methyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate; 
 ethyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate; 
 1-(4-(7-acetyl-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 1-ethyl-3-(4-(4-morpholino-7-pivaloyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 1-(4-(6-acetyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 1-ethyl-3-(4-(4-morpholino-6-pivaloyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-(2,2,2-trifluoroethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(4-(7-(2-hydroxyacetyl)-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-ethyl 2-(4-(3-ethylureido)-3-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(3-fluoro-4-(3-(2-hydroxyethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-cyclopropylureido)-3-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-ethyl-3-(5-(7-methyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)thiazol-2-yl)urea; 
 (S)-ethyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate; 
 (S)-1-(2,5-difluoro-4-(7-methyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-1-ethyl-3-(3-methyl-4-(7-methyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(3-fluoro-4-(7-methyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-ethyl 2-(4-(3-(3-hydroxyphenyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-(2-aminoethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-(2-amino-2-oxoethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-2-(3-(4-(6-(ethoxycarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)ureido)acetic acid; 
 (S)-ethyl 2-(5-(3-ethylureido)pyrazin-2-yl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-(4-(6-(1-acetylpiperidin-4-yl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-fluorophenyl)-3-ethylurea; 
 (S)-ethyl 4-(3-methylmorpholino)-2-(4-(3-(pyridin-3-yl)ureido)phenyl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-(4-(hydroxymethyl)phenyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-(2-fluoroethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 4-(3-methylmorpholino)-2-(4-(3-(pyridin-4-yl)ureido)phenyl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-methyl 4-(2-(4-(3-ethylureido)-3-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)piperidine-1-carboxylate; 
 (S)-1-(4-(6-(1-acetylpiperidine-4-carbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-2-fluorophenyl)-3-ethylurea; 
 (S)-ethyl 2-(4-(3-(2-acetamidoethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-(2-(methylamino)-2-oxoethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-ethyl-3-(2-fluoro-4-(4-(3-methylmorpholino)-6-(piperidine-4-carbonyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-4-(2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)-4-oxobutanamide; 
 (S)-tert-butyl 4-((2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)methyl)piperidine-1-carboxylate; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-(tetrahydro-2H-pyran-4-carbonyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-(piperidin-4-ylmethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-ethyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-(3-(2-oxopyrrolidin-1-yl)propanoyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)—N-(4-(2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)-4-oxobutyl)acetamide; 
 (S)-4-(2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)butanoic acid; 
 (S)—N-(3-(2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)-3-oxopropyl)-N-methylacetamide; and 
 (S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-(3-ureidopropanoyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; or a pharmaceutically acceptable salt thereof 
 
     
     
         16 . A compound of  claim 1  selected from the group consisting of:
 (S)-1-(2,6-difluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-1-(2,3-difluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea; 
 (S)-ethyl 2-(4-(3-ethylureido)-2,5-difluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(4-(3-ethylureido)-2,6-difluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 tert-butyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-tert-butyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; tert-butyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-cyclopropyl-3-(3-fluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 1-cyclopropyl-3-(3-fluoro-4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-cyclopropyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 1-ethyl-3-(3-fluoro-4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 ethyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-methyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-tert-butyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 1-ethyl-3-(3-fluoro-4-(6-methyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-cyclopropylurea; ethyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-ethylurea; 
 (S)-1-ethyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 1-cyclopropyl-3-(3-fluoro-4-(6-methyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(3-fluoro-4-(6-methyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 1-(4-(6-acetyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-ethylurea; methyl 2-(4-(3-ethylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-cyclopropyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-1-ethyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-2-(4-(3-cyclopropylureido)-2-fluorophenyl)-N,N-dimethyl-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide; 
 1-(4-(6-acetyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-cyclopropylurea; 
 (S)-ethyl 2-(2-fluoro-4-(3-(2-hydroxyethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-ethyl 2-(2-fluoro-4-(3-(2-fluoroethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; methyl 2-(2-fluoro-4-(3-(2-fluoroethyl)ureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 ethyl 2-(2-fluoro-4-(3-(2-fluoroethyl)ureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 ethyl 2-(2-fluoro-4-(3-(2-hydroxyethyl)ureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-1-cyclopropyl-3-(3-fluoro-4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)—-cyclopropyl-3-(3-fluoro-4-(6-isobutyryl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 methyl 2-(2-fluoro-4-(3-(2-hydroxyethyl)ureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-2-(4-(3-ethylureido)-2-fluorophenyl)-N,N-dimethyl-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide; 
 (S)-1-cyclopropyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; 
 (S)-2-(4-(3-cyclopropylureido)-2-fluorophenyl)-N,N-dimethyl-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxamide; 
 (R)-ethyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (R)-methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-methyl 2-(2-fluoro-4-(3-(2-hydroxyethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (R)-tert-butyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 (S)-methyl 2-(2-fluoro-4-(3-(2-fluoroethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate; 
 1-(3-fluoro-4-(6-isopropyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-hydroxyethyl)urea; 
 1-(3-fluoro-4-(6-isopropyl-4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-fluoroethyl)urea; 
 (S)-1-(3-fluoro-4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-fluoroethyl)urea; 
 (S)-1-(3-fluoro-4-(6-isopropyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-(2-hydroxyethyl)urea; 
 (R)-1-(4-(6-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-cyclopropylurea; 
 (S)-2-(4-(3-cyclopropylureido)-2-fluorophenyl)-N-isopropyl-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxamide; 
 (R)-1-cyclopropyl-3-(3-fluoro-4-(6-formyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; and 
 (R)-1-cyclopropyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-6-(methylsulfonyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea; or 
 a pharmaceutically acceptable salt thereof. 
 
     
     
         17 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof of  claim 1  together with a pharmaceutically acceptable carrier, optionally in combination with one or more other pharmaceutical compositions. 
     
     
         18 . A method for treating, controlling, delaying or preventing in a mammalian patient in need thereof one or more conditions selected from the group consisting of diseases and disorders associated with mTOR, wherein the method comprises the administration to said patient a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof. 
     
     
         19 . A method for the preparation of a compound of  claim 1 , comprising the steps of
 (a) reacting a compound of formula (III)   
       
         
           
           
               
               
           
         
         
           wherein Pg is a suitable protective group; A is a suitable leaving group; and m, n, o, X, R 2  have the meaning as indicated in  claim 1  either
 (a1) with a compound of formula T-X 0 , wherein X 0  is a suitable boronic acid or boronate ester functional group and T has the meaning as indicated in  claim 1  in a Suzuki reaction to yield a compound of formula (I), wherein R 1  is Pg; or 
 (a2) deprotect the compound of formula (II) to yield a compound of formula (IV) 
 
         
       
       
         
           
           
               
               
           
         
       
       and
     (b1) optionally, deprotect the product of step (a1) to yield a compound of formula (I), wherein R 1  is H followed by the optional step of reacting a compound of formula (I), wherein R 1  is H by a compound of formula R 1 —X 1 , wherein X 1  is a suitable leaving group and R 1  is defined as indicated in  claim 1  excluding H to yield a compound of formula (I), wherein R 1  is other than H; or   (b2) react a compound of formula (IV) with a compound of formula R 1 —X 1 , wherein X 1  is a suitable leaving group and R 1  is defined as indicated in  claim 1  excluding H to yield a compound of formula (V)     
 
       
         
           
           
               
               
           
         
         
           
             
               followed by reacting a compound of formula (V) with a compound of formula T-X 0 , wherein X 0  is a suitable boronic acid or boronate ester functional group and T has the meaning as indicated in  claim 1  in a Suzuki reaction to yield a compound of formula (I).