Compound derived from 8h pirido (2,3-d) pyrimidine 7 ONa 2,4,8 - trisustituida Pharmaceutical Composition and use for preparing a composition for Treatment of a disease and profilxis mediated CSBP / RK / p38 kinase

摘要

0 '! Or20) VRB or n (R10 ') OC (z) (cr10r20) VRB; R1' makes independent choice between halide, C1-4 tar, C1-4 alternative halogen tar, cyanogen, nitrate (cr10r20) and "nrdrd",(cr10r20) V'C (o) R12, SR5, s (o) R5, s (o) 2r5 o (cr10r20) v'or13; X is R2 ',Or2',Yes, that's it.(CH2) n N (R10) S (O) mR2(CH2) n N (R10) C (O) R2(CH2) n'NR4R14, (CH2) n'N (R2 ') (R2ö) or N (R10') RhNH-C (= N-CN) NRqRq ';X1 is n (R11),O, S (O) m or CR10R20; Rb is a residue H, C1-10alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-10alkyl, aryl, aryl-C1-10alkyl, heteroaryl, heteroaryl-C1-10alkyl, heterocyclyl or heterocyclyl-C1alkyl -10, where all of these moieties, excluding H, may be optionally substituted; Rh is selected from an optionally substituted C1-10 alkyl -CH2-C (O) -CH2-,-That's it. - that's it-CH2-C (O) N (R10) CH2-CH2--CH2-N (R10) C (O) CH2--CH2-CH (OR10) -CH2--CH2-C (O) O-CH2-CH2- or -CH2-CH2-O-C (O) CH2-;Rq and Rq 'are independently selected in each case from a moiety H, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-10 alkyl, C5-7 cycloalkenyl, C5-7 cycloalkenyl-C1-10 alkyl, aryl, aryl-C1-10alkyl, heteroaryl, heteroaryl-C1-10alkyl, heterocyclyl or heterocyclyl-C1-10alkyl where all residues except residue H are optionally substituted, or Rq and Rq 'together with the N to which linked they form an optionally substituted 5- to 7-membered heterocyclic ring, wherein said ring may contain an additional heteroatom selected from O, N or S; R2 is a residue H, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, aryl-C1-10 alkyl,heteroaryl, heteroaryl-C1-10alkyl, heterocyclyl or heterocyclyl-C1-10alkyl, and where each of these moieties, excluding H, may be optionally substituted; or R2 is the moiety (CR10R20) q'X1 (CR10R20) qC (A1) (A2) (A3) or (CR10R20) q'C (A1) (A2) (A3);R2 'is a residue H, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, aryl-C1-10alkyl, heteroaryl, heteroaryl-C1-10alkyl, heterocyclyl or heterocyclyl-C1-10alkyl, and where each of these residues, excluding H, may be optionally substituted; or R2ö is a residue H, C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkylalkyl, aryl, aryl-C1-10alkyl, heteroaryl, heteroaryl-C1-10alkyl, heterocyclyl or heterocyclyl-C1-10alkyl, and where each of these residues, excluding H, may be optionally substituted; or where R2ö is the residue (CR10R20) tX1 (CR10R20) qC (A1) (A2) (A3);A1 is an optionally substituted C1-10 alkyl; A2 is an optionally substituted C1-10 alkyl, A3 is H or is an optionally substituted C1-10 alkyl; R3 is a C1-10 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-10 alkyl, aryl, aryl-C1-10 alkyl, heteroaryl, heteroaryl-C1-10 alkyl, heterocyclyl or heterocyclyl-C1-10 alkyl , and where each of these moieties may be optionally substituted; R4 and R14 are each independently selected from H, C1-4alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-4alkyl, aryl, aryl-C1-4alkyl, heterocyclyl, C1-4alkyl heterocyclic, heteroaryl, heteroaryl-C1-4alkyl, and where each of these moieties,If h is not included, substitution is optional; or R4 and R14 together with the attached N form an alternative heterocyclic ring of four to seven members, wherein the ring can selectively contain an additional heteromorphic atom selected between O, s or N9; Each R4 'and R14' shall be individually selected between H or C14, or R4 'and R14, and together with N form a heterocyclic ring of 5 to 7 members, wherein the ring may select an additional heterocyclic atom between N9.R5 is independently selected between substances such as h, C1-4, c2-4, c2-4, c2-4 or nr4'r14,SR5 residues excluding snr4'r14;S (O) 2R5 which are SO2H and S (O) R5 which are SOH; R6 is independently selected in each occurrence from a moiety H, C1-10alkyl, C3-7cycloalkyl, heterocyclyl, heterocyclyl-C1-10alkyl, aryl, aryl-C1-10alkyl, heteroaryl or heteroaryl-C1-10alkyl, and where each of these residues, excluding H, may be optionally substituted; R9 is independently selected in each occurrence from H, C (Z) R6, optionally substituted C1-10 alkyl, optionally substituted aryl, or optionally substituted aryl-C1-14 alkyl; R9 'is independently selected in each case from H or C1-4alkyl; R10 and R20 are independently selected in each case from H or C1-4alkyl;R10 'is independently selected in each case with H or C1-4alkyl; R11 is independently selected in each case from H or C1-4alkyl; R12 is independently selected in each occurrence from a moiety H, C1-4alkyl, substituted halo-C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-4alkyl, C5-7cycloalkenyl, C5-7cycloalkenyl-C1-4alkyl, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, heterocyclyl or heterocyclyl-C1-4alkyl, and wherein each of these moieties, excluding H, it may be optionally substituted; R13 is independently selected in each occurrence from a moiety H, C1-4alkyl,halo-substituted C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-4alkyl, C5-7cycloalkenyl, C5-7cycloalkenyl-C1-4alkyl, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, heterocyclyl or heterocyclyl-C1-4alkyl, and where each of these moieties, excluding H, may be optionally substituted; each of Rd and Rd 'is independently selected in each case from a residue H, C1-4alkyl, C3-6cycloalkyl, cycloalkylC3-6-C1-4alkyl and where each of these residues, excluding H, can be optionally substituted;O RD and RD 'plus N form an optional aperiodic ring, which is replaced by 5 to 6 members, wherein the ring optionally contains an additional non atom selected from O, s or nr9;g is 0 or an integer that has the value 1, 2, 3, or 4; n 'is 0 or an integer that has a value from 1 to 10; m is 0 or an integer that has the value 1 or 2; q is 0 or an integer that has a value from 1 to 10; q 'is 0 or an integer that has a value from 1 to 6; t is an integer that has a value from 2 to 6; v is 0 or an integer that has the value 1 or 2; v 'is 0 or an integer that has the value 1 or 2; Z is independently selected in each case from O or S; and a pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof. Pharmaceutical composition that comprises it. Use to prepare a pharmaceutical composition for treatment,It includes prevention, a disease treated by quinassa CSBP / rk / p38.