Kinase inhibitor compounds

Abstract

The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of kinase-mediated processes, and treatment of disease and disease symptoms, particularly those mediated by certain kinase enzymes.

1 - 8 . (canceled) 
     
     
         9 . A method of treating a disease or disease symptom modulated by any one or any combination of the kinases selected from VEGFR, PDGFR, KIT, and Flt-3, in a subject in need thereof comprising administering to the subject an effective amount of a compound of formula (I), 
       
         
           
           
               
               
           
         
         wherein Cy is a cyclic structure that can be cycloalkyl or heterocyclic, each optionally substituted with Z 1 , Z 2  and Z 3 ; 
         R 1 , R 2 , R 3 , R 4 , and R 5  are each independently: 
         (1) hydrogen or R 6 , where R 6 , is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z 1 , Z 2  and one or more (preferably, one or two) groups Z 3 ; 
         (2) —OH or —OR 6 ; 
         (3) —SH or —SR 6 ; 
         (4) —C(O) 2 H, —C(O) q R 6 , —C(O)NR 7 R 8 , —C(O)C(O)NR 7 R 8 , or —O—C(O) q R 6 , where q is 1 or 2; 
         (5) —SO 3 H or —S(O) q NR 7 R 8 ; 
         (6) halo; 
         (7) cyano; 
         (8) nitro; 
         (9) —Z 4 —NR 7 R 8 ; 
         (10) —Z 4 —N(R 9 )—Z 5 —NR 10 R 11 ; 
         (11) —Z 4 —N(R 12 )—Z 5 —R 6 ; 
         (12) —P(O)(OR 6 ) 2 ; 
         R 7 , R 8 , R 9 , R 10 , R 11  and R 12  are each independently: 
         (1) hydrogen or R 6 ; 
         (2) R 7  and R 8  together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with Z 1 , Z 2  and Z 3 ; or 
         (3) any two of R 9 , R 10  and R 11  together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with Z 1 , Z 2  and Z 3 ; 
         Z 1 , Z 2  and Z 3  are each independently: 
         (1) hydrogen or Z 6 , where Z 6  is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl; (ii) a group (i) which is itself substituted by one or more of the same or different groups (i); or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (13); 
         (2) —OH or —OZ 16 ; 
         (3) —SH or —SZ 16 ; 
         (4) —C(O) 2 H, C(O) q Z 16 , —C(O)NZ 17 Z 18 , —C(O)C(O)NZ 17 Z 18 , or —O—C(O) q Z 16 , where q is 1 or 2; 
         (5) —SO 3 H, —S(O) q Z 16 , or —S(O) q NZ 17 Z 18 ; 
         (6) halo; 
         (7) cyano; 
         (8) nitro; 
         (9) —Z 4 —NZ 17 Z 18 ; 
         (10) —Z 4 —N(Z 18 )—Z 5 —NZ 19 Z 20 ; 
         (11) oxo; 
         (12) —O—C(O)—Z 16 ; 
         (13) any two of Z 1 , Z 2  and Z 3  may together be alkylene, alkenylene, aryl, heteroaryl, or heterocyclo completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached; 
         Z 4  and Z 5  are each independently 
         (1) a single bond; 
         (2) —Z 11 —S(O) q —Z 12 —; 
         (3) —Z 11 —C(O)—Z 12 —; 
         (4) —Z 11 —O—Z 12 —; 
         (5) —Z 11 —S—Z 12 —; 
         (6) —Z 11 —O—C(O)—Z 12 —; or 
         (7) —Z 11 —C(O)—O—Z 12 ; 
         Z 11  and Z 12  are each independently 
         (1) a single bond; 
         (2) alkylene; 
         (3) alkenylene; or 
         (4) alkynylene; 
         each Z 16  is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl, each optionally substituted with one or more of the following groups: 
         (2) —OH or —OZ 21 ; 
         (3) —SH or —SZ 21 ; 
         (4) —C(O) 2 H, C(O) q Z 21 , —C(O)NZ 17 Z 18 , —C(O)C(O)NZ 17 Z 18 , or —O—C(O) q Z 21 , where q is 1 or 2; 
         (5) —SO 3 H, —S(O) q Z 21 , or —S(O) q NZ 17 Z 18 ; 
         (6) halo; 
         (7) cyano; 
         (8) nitro; 
         (9) —Z 4 —NZ 17 Z 18 ; 
         (10) —Z 4 —N(Z 18 )—Z 5 —NZ 19 Z 20 ; 
         (11) oxo; 
         (12) —O—C(O)—Z 21 ; 
         each Z 17  is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl; 
         each Z 18  is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl; 
         each Z 19  is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl; 
         each Z 20  is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl; 
         each Z 21  is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl; each Z 22  is independently is, 
         (2) —OH or —OZ 21 ; 
         (3) —SH or —SZ 21 ; 
         (4) —C(O) 2 H, C(O) q Z 21 , —C(O)NZ 21 Z 21 , —C(O)C(O)NZ 21 Z 21 , or —O—C(O) q Z 21 , where q is 1 or 2; 
         (5) —SO 3 H, —S(O) q Z 21 , or —S(O) q NZ 21 Z 21 ; 
         (6) halo; 
         (7) cyano; 
         (8) nitro; 
         (9) —Z 4 —NZ 21 Z 21 ; 
         (10) —Z 4 —N(Z 21 )—Z 5 —NZ 21 Z 21 ; 
         (11) oxo; 
         (12) —O—C(O)—Z 21 ; 
         where Z 17  and Z 18 , or Z 19  and Z 20 , together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with 1, 2, or 3 independent Z 22 ; and 
         where any two of Z 18 , Z 19  or Z 20  together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with 1, 2 or 3 independent Z 22 ; 
         provided said compound is other than a compound of formula IIa or IIb 
       
       
         
           
           
               
               
           
         
         or pharmaceutical salt, solvate or hydrate thereof. 
       
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 9 , wherein the disease or disease symptom is cancer, tumor, or a proliferative disorder. 
     
     
         13 - 30 . (canceled)