Treatment for stroke management

A method of treating a CNS injury to the brain, in a mammal in need of such treatment, which method comprises administering to said mammal an effective amount of a cytokine suppressive binding protein compound represented by the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• X and X′ each independently represent —(CH2)m —Y—(CH2)n—, wherein m and n represent integers within the range of from 0-4, such that the sum of m and n is from 0-6;
• Y represents a member selected from the group consisting of:
• a direct bond;
• O;
• S(O)y, with y equal to 0, 1 or 2;
• NRq′, with Rq′ as defined below;
• C(O);
• OC(O);
• C(O)O;
• SOxNRq′ with x equal to 1 or 2 and Rq′ as defined below;
• NRq′SOx;
• C(O)NRq′ and NRq′ C(O);
• represents a 4 to 10 membered non-aromatic heterocycle containing at least one N atom, and optionally containing 1-2 additional N atoms and 0-1 O or S atom;
• Rx represents H, C1-6alkyl(Rq)3, C3-8cycloalkyl, OC1-6alkyl(Rq)3 or C(O)C1-6alkyl(Rq)3;
• each R independently represents a member selected from the group consisting of:
• halo;
• hydroxy;
• C1-6alkyl(Rq)3;
• OC1-6alkyl(Rq)3;
• C3-8cycloalkyl(Rq)3;
• CN;
• CONH2;
• CONHC1-6alkyl(Rq)3;
• CON(C1-6alkyl(Rq)3)2;
• NH2;
• NHC1-6alkyl(Rq)3;
• NHC3-8cycloalkyl;
• N(C1-6alkyl(Rq)3)2;
• CON(C3-8cycloalkyl)(C1-6alkyl(Rq)3);
• CO)2H;
• CO2C1-6alkyl(Rq)3;
• C(O)C1-6alkyl(Rq)3;
• aryl(Rq)3;
• heterocyclyl(Rq)3;
• heteroaryl(Rq)3;
• CF3;
• SH;
• NO2;
• NHSO2C1-6alkyl(Rq)3;
• NHSO2 aryl(Rq)3, NHSO2 heteroaryl(Rq)3;
• N(Rq′)C(O) C1-6alkyl(Rq)3;
• NRq′C(O)NH(C1-6alkyl(Rq)3);
• C2-4alkenyl(Rq)2-3 and C2-4alkynyl(Rq)1-3;
• each R″ independently represents a member selected from the group consisting of:
• halo;
• hydroxy;
• C C1-6alkyl(Rq)3;
• OC1-6alkyl(Rq)3;
• C3-8cycloalkyl(Rq)3;
• CN;
• CONH2;
• CONHC1-6alkyl(Rq)3;
• CON(C1-6alkyl(Rq)3)2;
• NH2;
• NHC1-6alkyl(Rq)3;
• NHC3-8cycloalkyl;
• N(C1-6alkyl(Rq)3)2;
• CON(C3-8cycloalkyl)(C1-6alkyl(Rq)3);
• CO2H;
• CO2C1-6alkyl(Rq)3;
• C(O)C1-6alkyl(Rq)3;
• aryl(Rq)3;
• heterocyclyl(Rq)3;
• heteroaryl(Rq)3;
• CF3;
• SH;
• NO2;
• SOy C1-6alkyl(Rq)3, with y as defined above;
• SO2NH2;
• SO2NHC1-6alkyl(Rq)3;
• SO2N(C1-6alkyl(Rq)3)2;
• NHSO2C1-6alkyl(Rq)3;
• NHSO2aryl(Rq)3, NHSO2 heteroaryl(Rq)3;
• N(Rq)C(O)C1-6alkyl(Rq)3;
• NRq′C(O)NH(C1-6alkyl(Rq)3);
• C2-4alkenyl(Rq)2-3 and C2-4alkynyl(Rq)1-3;
• each R′ independently represents a member selected from the group consisting of:
• CONH2;
• CONHC1-6alkyl(Rq)33;
• CON(C1-6alkyl(Rq)3)2;
• CONHC3-8cycloalkyl(Rq)3;
• CON(C3-8cycloalkyl(Rq)3)2;
• CON(C3-8cycloalkyl)(C1-6alkyl(Rq)3));
• CO2H;
• CO2C1-6alkyl(Rq)3;
• C(O)C1-6alkyl(Rq)3;
• CO2C3-8cycloalkyl(Rq)3;
• C(O)C3-8cycloalkyl(Rq)3;
• —[C(O)(CH2)j—CR5R6—(CH2)k—NR7]p—R8;
• —C(O)heterocyclyl(Rq)3, —CON[C1-6alkyl(Rq)3]C3-8cycloalkyl(Rq)3];
• —C(O)aryl(Rq)3;
• —C(O)heteroaryl(Rq)3;
• hydroxy;
• C1-6alkyl(Rq)3;
• C3-8cycloalkyl(Rq)3;
• OC1-6alkyl(Rq)3;
• OC3-8cycloalkyl(Rq)3;
• heterocyclyl(Rq)3;
• CN;
• NH(Rq″);
• NHC1-6alkyl(Rq)3;
• N(C1-6alkyl(Rq)3)2;
• NHC3-8cycloalkyl(Rq)3;
• N(C3-8cycloalkyl(Rq)3)2;
• CF3;
• SH;
• NO2;
• C2-4alkenyl(Rq)2-3, aryl(Rq)3)2;
• heteroaryl(Rq)3;
• C2-4alkynyl(Rq)1-3;
• OC(O)C3-8cycloalkyl(Rq)3;
• SO2NH2;
• SO2NH C1-6alkyl(Rq)3;
• SO2N(C1-6alkyl(Rq)3)2;
• NH SO2C1-6alkyl(Rq)3;
• NHSO2aryl(Rq)3;
• NHSO2heteroaryl(Rq)3;
• OC(O)heterocyclyl(Rq)3;
• N(Rq′)C(O) C1-6alkyl(Rq)3;
• NRq′C(O)NH(C1-6alkyl(Rq)3;
• OC(O)C1-6alkyl(Rq)3;
• —OC(O)aryl(Rq)3;
• OC(O)heteroaryl(Rq)3;
• —C(═NRq′)NH2;
• —C(═NRq′)NH C1-6alkyl(Rq)3;
• —C(═NRq′)N(C1-6alkyl(Rq)3)2;
• —O—[C(O)—(CH2)j—CR5R6—(CH2)k—NR7]p-R8 and —[NR7(CH2)k— CR5R6—(CH2)j —C(O)]p—OR9
• wherein j and k independently represent integers of from 0-3;
• R5 and R6 are independently H, aryl, C1-6alkyl(Rq)3, or CR5R6 in combination represents a 3, 4, 5 or 6 membered cycloalkyl or heterocyclyl group, an aryl group or a heteroaryl group;
• p represents 1, 2 or 3, with the proviso that when p represents 1, CR5R6 represents a 3, 4, 5 or 6 membered cycloalkyl group or a heterocyclyl group, an aryl group or a heteroaryl group, and at least one of j and k is 1, 2 or 3;
• R7 and R8 are independently H, C1-6 alkyl or aryl;
• R9 represents H, a negative charge balanced by a positively charged group or a protecting group;
• Rqrepresents a member selected from the group consisting of:
• Rq′;
• halo;
• CN;
• CO2H;
• CO2 C1-4alkyl;
• C(O)C1-4alkyl;
• NH(Rq″);
• aryl(Ra)3;
• heteroaryl(Ra)3;
• NHC1-4alkyl;
• N(C1-4alkyl)2;
• CONH2;
• SH;
• S(O)y C1-6alkyl(Ra)3;
• C(O)NH C1-6alkyl (Ra)3;
• C(O)N(C1-6alkyl(Ra)3)2;
• C3-8cycloalkyl;
• NHC(NH)NH2;
• heteroalkyl(Ra)3;
• —NHC(O)NH2;
• wherein
• independently represent mono or bicyclic ring systems, non-aromatic or partially aromatic, containing from 5-10 ring atoms, 1-4 of which are N and 0-1 of which are O or S(O)y, with y equal to 0, 1 or 2, optionally containing 1-2 carbonyl groups;
• each Ra independently represents a member selected from the group consisting of:
• H, C1-6 alkyl, OC1-6 alkyl, aralkyl, substituted aralkyl, heteroaralkyl, substituted heteroaralkyl, aralkoxy, substituted aralkoxy, halo, hydroxy, CN, CONH2, CONHC1-6 alkyl, CON(C1-6 alkyl)2, CO2H, CO2C1-6 alkyl, C(O)C1-6alkyl, phenyl, CF3, SH, NO2, SOy C1-6alkyl, with y as defined above;
• SO2NH2, SO2NH C1-6alkyl, NH SO2(substituted aryl), NHSO2(substituted heteroaryl), NH SO2C1-6 alkyl, NH SO2aryl, NH SO2heteroaryl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, NHC(O)C1-6alkyl, NHC(O)NH(C1-6alkyl), C2-4alkenyl and C2-4 alkynyl;
• Rq′ represents H, OH, C1-4alkyl, —O C1-4alkyl, aryl or C(O) C1-4alkyl, and
• Rq″ represents H, OH or O C1-4alkyl.