Bicyclic pyrimidine compounds
The present invention provides compounds of the Formula I: wherein X is a bond or CH 2 ; R is selected from the group consisting of R 1 and R 2 are each independently selected from the group consisting of CH and N; R 3 is H or CH 3 ; R 4 is H or CH 3 ; L is selected from the group consisting of —O(CH 2 ) 3 —, —C(O)NH(CH 2 ) 2 —, —CH 2 C(O)NH(CH 2 ) 2 —, —(CH 2 ) 3 N(C(O)CH 3 )CH 2 —, —(CH 2 ) 2 N(C(O)CH 3 )CH 2 —, —(CH 2 ) 3 NH—, (CH 2 ) 2 OCH 2 —, —(CH 2 ) 4 —, —(CH 2 ) 2 NHCH 2 —, —(CH 2 ) 3 O—, and —CH 2 O(CH 2 ) 2 —; or a pharmaceutically acceptable salt thereof. Compounds of this invention are autotaxin inhibitors.
1. A compound of the of the Formula I:
wherein X is a bond or CH 2 ;
R is selected from the group consisting of
R 1 and R 2 are each independently selected from the group consisting of CH and N;
R 3 is H or CH 3 ;
R 4 is H or CH 3 ;
L is selected from the group consisting of —O(CH 2 ) 3 —, —C(O)NH(CH 2 ) 2 —, —CH 2 C(O)NH(CH 2 ) 2 —, —(CH 2 ) 3 N(C(O)CH 3 )CH 2 —, —(CH 2 ) 2 N(C(O)CH 3 )CH 2 —, —(CH 2 ) 3 NH—, (CH 2 ) 2 OCH 2 —, —(CH 2 ) 4 —, —(CH 2 ) 2 NHCH 2 —, —(CH 2 ) 3 O—, and —CH 2 O(CH 2 ) 2 —;
or a pharmaceutically acceptable salt thereof.
2. A compound or salt according to claim 1 wherein R is
3. A compound or salt according to claim 2 wherein R 1 is CH.
4. A compound or salt according to claim 3 wherein R 2 is N.
5. A compound or salt according to claim 4 wherein L is selected from the group consisting of —(CH 2 ) 4 —, —O(CH 2 ) 3 —, —(CH 2 ) 2 OCH 2 —, —(CH 2 ) 3 O—, and —CH 2 O(CH 2 ) 2 —.
6. A compound or salt according to claim 5 wherein L is —(CH 2 ) 2 OCH 2 —.
7. A compound or salt according to claim 5 wherein L is —O(CH 2 ) 3 —.
8. A compound or salt according to claim 3 wherein L is selected from the group consisting of —(CH 2 ) 2 N(C(O)CH 3 )CH 2 —, —(CH 2 ) 3 N(C(O)CH 3 )CH 2 —, and —CH 2 C(O)NH(CH 2 ) 2 —.
9. A compound or salt according to claim 1 wherein X is a bond.
10. A compound or salt according to claim 1 wherein X is CH 2 .
11. A compound or salt according to claim 1 that is 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-2-[2-(1H-1,2,3-triazol-4-yl)ethoxy]ethanone
12. A compound or salt according to claim 1 that is that is 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]-2-[2-(1H-1,2,3-triazol-4-yl)ethoxy]ethanone
13. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, according to claim 1 , in combination with one or more pharmaceutically acceptable carriers, diluents, or excipients.
14. An intermediate compound of the formula:
15. An intermediate compound of the formula: