| 主权项 |
1. A method of inhibiting cytochrome P450 monooxygenase comprising administering to a patient a compound represented by a formula:
X-A-B—X′ wherein: X is a lipophilic group containing from 1 to 12 carbon atoms optionally containing from 1 to 3 heteroatoms independently selected from the group consisting of O, S, and N, A is —OCON(R2)-, —S(O)nN(R2)-, —CON(R2)-, —COCO(NR2)-, —N(R2)CON(R2)-, —N(R2)S(O)nN(R2)-, N(R2)CO or —N(R2)COO—; B is —(CG1G2)m-, wherein m is 2-6 and wherein G1 and G2 are the same or different and wherein each G1 and G2 independently is selected from the group consisting of a bond, H, halo, haloalkyl, OR, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heterocycloalkyl wherein each optional substitution independently is selected from the group consisting of alkyl, halo, cyano, CF3, OR, C3-C7 cycloalkyl, C5-C7 cycloalkenyl, R6, OR2, SR2, N(R2)2, OR3, SR3, NR2R3, OR6, SR6, and NR2R6, and wherein G1 and G2, together with the atoms to which they are attached, optionally may form a 3-7-membered carbocyclic or heterocyclic ring containing up to three heteroatoms selected from the group consisting of N, S and O, and wherein said ring optionally may be substituted with up to 3 R7 moieties, wherein neither G1 nor G2 is OH, X′ is wherein J is selected from: —N(D)-SOn—, —N(D)-COn—, —N(D)-(R8)q—, —N(CO-D)-(R8)q—, —N(SOn-D)-(R8)q—, —SOn—N(D)-(R8)q—, or —COn—N(D)-(R8)q—, wherein D is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, heteroaryl, heteroaralkyl or aralkyl, O-alkyl, O-cycloalkyl, O-cycloalkylalkyl, O-heterocycloalkyl, O-heterocycloalkylalkyl, O-heteroaralkyl, O-aralkyl, N(R2)-alkyl, N(R2)-cycloalkyl, N(R2)-cycloalkylalkyl, N(R2)-heterocycloalkyl, N(R2)-heterocycloalkylalkyl, N(R2)-heteroaralkyl, N(R2)-aralkyl, wherein D optionally is substituted by alkyl, halo, nitro, cyano, O-alkyl, or S-alkyl; wherein R is H, alkyl, haloalkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, and heteroaralkyl; wherein each R2 is independently selected from the group consisting of H, C1-C12 alkyl, C3-C8 cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, and heterocycloalkyl each further optionally substituted with one or more substituents selected from the group consisting of C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocyclo; halo, OR, ROH, R-halo, NO2, CN, COnR, CON(R)2, C(S)R, C(S)N(R)2, SOnN(R)2, SR, SOnR, N(R)2, N(R)COnR, NRS(O)nR, NRC[═N(R)]N(R)2, N(R)N(R)COnR, NRPOnN(R)2, NRPOnOR, oxo, ═N—OR, ═N—N(R)2, ═NR, ═NNRC(O)N(R)2, ═NNRCOnR, ═NNRS(O)nN(R)2, and ═NNRS(O)n(R); or each R2 is independently selected from the group consisting of C1-C6 alkyl; substituted by aryl or heteroaryl; which groups optionally are substituted with one or more substituents selected from the group consisting of halo, OR, ROH, R-halo, NO2, CN, COnR, CON(R)2, C(S)R, C(S)N(R)2, SOnN(R)2, SR, SOnR, N(R)2, N(R)COnR, NRS(O)nR, NRC[═N(R)]N(R)2, N(R)N(R)COnR, NRPOnN(R)2, NRPOnOR; R3 is C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, or heterocyclo; which groups optionally are substituted with one or more substituents selected from the group consisting of halo, OR2, R2-OH, R2-halo, NO2, CN, COnR2, C(O)N(R2)2, C(O)N(R2)N(R2)2, C(S)R2, C(S)N(R2)2, S(O)nN(R2)2, SR2, SOnR2, N(R)2, N(R2)COnR2, NR2S(O)nR2, NR2C[═N(R2)]N(R2)2, N(R2)N(R2)COnR2, oxo, ═N—OR2, ═N—N(R2)2, ═NR2, ═NNRC(O)N(R2)2, ═NNR2C(O)nR2, ═NNR2S(O)nN(R2)2, and ═NNR2S(O)n(R2); R6 is aryl or heteroaryl, wherein said aryl or heteroaryl optionally are substituted with one or more groups selected from the group consisting of aryl, heteroaryl, R2, R3, halo, OR2, R2OH, R2-halo, NO2, CN, COnR2, C(O)N(R2)2, C(O)N(R2)N(R2)2, C(S)R2, C(S)N(R2)2, S(O)nN(R2)2, SR2, SOnR2, N(R)2, N(R2)COnR2, NR2S(O)nR2, NR2C[═N(R2)]N(R2)2, N(R2)N(R2)COnR2, OC(O)R2, OC(S)R2, OC(O)N(R2)2, and OC(S)N(R2)2; R7 is H, oxo, C1-C12 alkyl; C3-C8 cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, or heterocycloalkyl, each further optionally substituted with one or more substituents selected from the group consisting of C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, heterocyclo; halo, OR, ROH, R-halo, NO2, CN, COnR, CON(R)2, C(S)R, C(S)N(R)2, SOnN(R)2, SR, SOnR, N(R)2, N(R)COnR, NRS(O)nR, NRC[═N(R)]N(R)2, N(R)N(R)COnR, NRPOnN(R)2, NRPOnOR, oxo, ═N—OR, ═N—N(R)2, ═NR, ═NNRC(O)N(R)2, ═NNRCOnR, ═NNRS(O)nN(R)2, and ═NNRS(O)n(R); R8 is alkyl, haloalkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, and heteroaralkyl; wherein n=1-2, and wherein q=0-1. |
