Aminopyrimidinecarboxamides as CXCR2 modulators

1. A compound comprising a compound from formula (1):

wherein R 1 and R 2 are independently selected from the group consisting of hydrogen, 2- or 3- or 4-halo-phenyl, heteroalkyl, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl;

wherein R 3 is selected from the group consisting of hydrogen, heteroalkyl, alkyl, aminoalkyl, aryl, arylalkyl, carboxyalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl, R 4 is selected from the group consisting of heteroalkyl, aminoalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl, or R 3 or R 4 are independently an ionizing group selected from the group consisting of carboxylates, amines, phosphonates, and phosphates;

wherein R 3 and R 4 are also independently selected from the group consisting of —B(R 5 R 6 ), —BF 3 − M + , —R 7 —B(R 5 R 6 ), —R 7 —BF 3 − M + , R 7 ,—C(O)—R 7 , —O—R 7 , —S(O) y —R 7 (wherein y=0, 1, or 2), —P(O)—(R 5 R 6 ) and —N(R 8 R 9 );

wherein R 7 is selected from the group consisting of alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl;

wherein M + is a Group I or a Group II metal;

wherein R 5 and R 6 are independently hydrogen, hydroxyl, aryloxy, or alkoxy, or wherein R 5 and R 6 together form a cyclic ester, or an acid anhydride (either mixed or symmetrical);

wherein R 8 and R 9 are independently selected from hydrogen, alkyl, haloalkyl, aryl, cycloalkyl, arylalkyl, heteroalkyl, hetercyclyl and heterocyclylalkyl; R 8 and R 9 are both oxygen to form a nitro group; or R 8 and R 9 together with the nitrogen to which they are attached, form a heterocyclyl; and

wherein n=1;

or pharmaceutical compositions thereof.

2. The compound of claim 1 wherein R 1 is hydrogen and R 2 is 4-fluoro-phenyl.

3. The compound of claim 1 wherein R 4 is 4-phenylboronic acid.

4. A pharmaceutical composition comprising a compound of formula (1):

wherein R 1 and R 2 are independently selected from the group consisting of hydrogen, 2- or 3- or 4-halo-phenyl, heteroalkyl, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl;

wherein R 3 and R 4 are independently-selected from the group consisting of hydrogen, heteroalkyl, alkyl, aminoalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl, or R 3 and R 4 are independently an ionizing group selected from the group consisting of carboxylates, amines, phosphonates, and phosphates;

wherein R 3 and R 4 are also independently selected from the group consisting of —B(R 5 R 6 ), —BF 3 − M + , —R 7 —B(R 5 R 6 ), —R 7 —BF 3 − M + , R 7 ,—C(O)—R 7 , —O—R 7 , —S(O)—R 7 , —P(O)—(R 5 R 6 ) and —N(R 8 R 9 ); wherein y=0, 1, or 2;

wherein R 7 is selected from the group consisting of alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl;

wherein M + is a Group I or a Group II metal;

wherein R 5 and R 6 are independently selected from the group consisting of hydrogen, hydroxyl, aryloxy, or alkoxy, or wherein R 5 and R 6 together form a cyclic ester, or an acid anhydride;

wherein R 8 and R 9 are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, cycloalkyl, arylalkyl, heteroalkyl, hetercyclyl and heterocyclylalkyl; R 8 and R 9 are both oxygen to form a nitro group; or R 8 and R 9 together with the nitrogen to which they are attached, form a heterocyclyl; and

wherein n=1.

5. The pharmaceutical composition of claim 4 , wherein R 1 is hydrogen and R 2 is 4-fluoro-phenyl.

6. The pharmaceutical composition of claim 4 , wherein R 4 is 4-phenylboronic acid.