Heterocyclic compounds
This invention relates to heterocyclic compounds of the formulas shown in the specification. It also relates to methods for treating inflammatory diseases or immune diseases, developmental or degenerative diseases, and tissue injuries with one of the heterocyclic compounds.
1. A compound of the following formula:
wherein
each Q and U is CH or N, provided that one of Q and U is N;
each of X, Y, and Z, independently, is C 1-5 alkylene or deleted;
m is 0, 1, 2, 3, 4, or 5;
n is 1;
p is 1 or 2;
R 1 is H, C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, heteroaryl, halo, CN, OR a , COOR a , OC(O)R a , C(O)R a , C(O)NR a R b , or NR a R b ;
R 2 is C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, heteroaryl, or C 1 -C 10 alkyl, optionally substituted with C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, or N(R c R d );
R 3 , independently, is C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, heteroaryl, halo, CN, OR e , COOR e , OC(O)R e , C(O)R e , C(O)NR e R f , or NR e R f ; or R 3 is C 1-5 alkylene bonded to two carbon atoms of the ring to which it is attached or C 2-8 alkylene bonded to one carbon atom of the ring to which it is attached; and
R 4 is P(═O)(OR g )(OR i ), P(═O)(NHR g )(OR i ), P(═O)(NR g )(NR i ), S(═O) 2 OR g , or S(═O) 2 R g ;
in which each of R a , R b , R c , R d , R e , R f , R g and R i , independently, is H, C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, heteroaryl, or —C(O)R, R being H, C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, or heteroaryl; or R a and R b are linked and together form C 2-8 alkylene, R c and R d are linked and together form C 2-8 alkylene, R e and R f are linked and together form C 2-8 alkylene, or R g and R i are linked and together form C 1-5 alkylene.
2. The compound of claim 1 , wherein Q is CH and U is N.
3. The compound of claim 1 , wherein X is —CH 2 —, —CH 2 CH 2 — or —CH 2 CH 2 CH 2 — and p is 1.
4. The compound of claim 1 , wherein Y is —CH 2 or deleted and Z is —CH 2 —.
5. The compound of claim 1 , wherein R 2 is C 1-5 alkyl substituted N(R c R d ).
6. The compound of claim 5 , wherein R 2 is —CH 2 CH 2 CH 2 —N(R c R d ), in which R c is H and R d is C 1 -C 10 alkyl, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, or heteroaryl, or R c and R d are linked and together form C 4-6 alkylene.
7. The compound of claim 1 , wherein m is 0, 1, or 2; R 1 is NH 2 ; and R 3 is C 1 -C 3 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 8 heterocycloalkyl, aryl, heteroaryl, halo, CN, OR e , or C(O)NR c R f ; or R 3 is C 1-2 alkylene bonded to two carbon atoms of the ring to which it is attached or C 2-5 alkylene bonded to one carbon atom of the ring to which it is attached.
8. The compound of claim 1 , wherein R 4 is P(═O)(OH) 2 , P(═O)(OH)(OCH 2 CH 3 ), P(═O)(OCH 2 CH 3 ) 2 ,
S(═O) 2 OH, S(═O) 2 CH 3 , or S(═O) 2 Ph.
9. The compound of claim 8 , wherein m is 0, 1, or 2; p is 1; X is —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —; Y is —CH 2 or deleted and Z is —CH 2 —; R 1 is NH 2 ; R 2 is C 1-5 alkyl substituted N(R c R d ); and R 3 is C 1 -C 3 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 8 ttbonded to two carbon atoms of the ring to which it is attached or C 2-5 alkylene bonded to one carbon atom of the ring to which it is attached.
10. The compound of claim 1 , wherein the compound is selected from the groups consisting of the following compounds: