Patent ID: 6576655
Filing Date: 2003-06-10
Classification: A61P,C07C,C07D,Y10S

Abstract:
A compound of formula (VIII): wherein Ff is F(â€”K)m(â€”Yâ€”Z)q in which F is a fullerene core; each K, independently, is â€”OH, â€”SH, â€”NH2, â€”NHOH, â€”SO3H, â€”OSO3H, â€”CO2H, â€”CONH2, â€”CONHNH2, â€”P(OH)3, â€”PO(OH)2, â€”Oâ€”PO(OH)2, â€”Oâ€”PO(OH)â€”Oâ€”PO(OH)2, â€”Oâ€”PO(Oâˆ’)â€”Oâ€”CH2CH2â€”NH3+, â€”Oâ€”PO(Oâˆ’)â€”Oâ€”CH2CH2â€”N+(CH3)3, -glycoside, â€”OCH3, â€”OCH2(CHOH)4â€”CH2OH, â€”OCH2(CHOH)2â€”CH2OH, â€”NHâ€”CH2â€”CO2H, â€”[CH(CO2H)â€”CH2]1-100â€”OH, â€”[CH(CO2Ra)â€”CH2]1-100â€”OH, â€”[C(CH3)(CO2H)â€”CH2]1-100â€”OH, â€”[C(CH3)(CO2Ra)â€”CH2]1-100â€”OH, â€”N(OH)2, â€”NH3+, â€”N+H2Ra, â€”N+HRaRb, or â€”N+RaRbRc; each Y is -A-Bâ€”, in which A is â€”Oâ€”, â€”NHâ€”, â€”Sâ€”, â€”COâ€”Oâ€”, â€”Oâ€”COâ€”, â€”Oâ€”COâ€”Oâ€”, â€”Oâ€”COâ€”NHâ€”, â€”NHâ€”COâ€”NHâ€”, â€”COâ€”NHâ€”, or â€”NHâ€”COâ€”; and B is â€”Raâ€”Oâ€”[Si(CH3)2â€”Oâ€”]1-100, C1-2000 alkyl, C6-40 aryl, C7-2000 alkylaryl, C7-2000 arylalkyl, (C1-30 alkyl ether)1-100, (C6-40 aryl ether)1-100, (C7-2000 alkylaryl ether)1-100, (C7-2000 arylalkyl ether)1-100, (C1-30 alkyl thioether)1-100, (C6-40 aryl thioether)1-100, (C7-2000 alkylaryl thioether)1-100, (C7-2000 arylalkyl thioether)1-100, (C2-50 alkyl ester)1-100, (C7-2000 aryl ester)1-100, (C8-2000 alkylaryl ester)1-100, (C8-2000 arylalkyl ester)1-100, â€”Raâ€”COâ€”Oâ€”(C1-30 alkyl ether)1-100, â€”Raâ€”COâ€”Oâ€”(C6-40 aryl ether)1-100, â€”Raâ€”COâ€”Oâ€”(C7-2000 alkylaryl ether)1-100, â€”Raâ€”COâ€”Oâ€”(C7-2000 arylalkyl ether)1-100, (C4-50 alkyl urethane)1-100, (C14-60 aryl urethane)1-100, (C10-2000 alkylaryl urethane)1-100, (C10-2000 arylalkyl urethane)1-100, (C5-50 alkyl urea)1-100, (C14-60 aryl urea)1-100, (C10-2000 alkylaryl urea)1-100, (C10-2000 arylalkyl urea)1-100, (C2-50 alkyl amide)1-100, (C7-60 aryl amide)1-100, (C8-2000 alkylaryl amide)1-100, (C8-2000 arylalkyl amide)1-100, (C3-30 alkyl anhydride)1-100, (C8-50 aryl anhydride)1-100, (C9-2000 alkylaryl anhydride)1-100, (C9-2000 arylalkyl anhydride)1-100, (C2-30 alkyl carbonate)1-100, (C7-50 aryl carbonate)1-100, (C8-2000 alkylaryl carbonate)1-100, (C8-2000 arylalkyl carbonate)1-100, â€”Raâ€”Oâ€”COâ€”NHâ€”(Rb or Arâ€”Rb â€”Ar)â€”NHâ€”COâ€”Oâ€”(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, â€”Raâ€”Oâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, â€”Raâ€”Oâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, â€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”, â€”Raâ€”Oâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100â€”Rcâ€”Oâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”, â€”Raâ€”NHâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, â€”Raâ€”NHâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, â€”Raâ€”NHâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100â€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”, â€”Raâ€”NHâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100â€”Rcâ€”Oâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”Oâ€”, â€”Raâ€”Oâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”NHâ€”(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, â€”Raâ€”NHâ€”COâ€”NHâ€”(Rb or Arâ€”Rbâ€”Ar)â€”NHâ€”COâ€”NHâ€”(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, or a bond; each Z, independently, is G D, wherein G is â€”Raâ€”, â€”Raâ€”Arâ€”, â€”Arâ€”Raâ€”, or â€”Arâ€”; and D is â€”H, â€”OH, â€”SH, â€”NH2, â€”NHOH, â€”SO3H, â€”OSO3H, â€”CO2H, â€”CONH2, â€”CONHNH2, â€”CH(NH2)â€”CO2H, â€”NHâ€”CH2â€”CO2H, â€”P(OH)3, â€”PO(OH)2, â€”Oâ€”PO(OH)2, â€”Oâ€”PO(OH)â€”Oâ€”PO(OH)2, â€”Oâ€”PO(Oâˆ’)â€”Oâ€”CH2CH2NH3+, â€”Oâ€”PO(Oâˆ’)â€”Oâ€”CH2CH2â€”N+(CH3)3, -glycoside, -oligosaccharide, â€”CO-glycoside, â€”CO-oligosaccharide, â€”OCH3, â€”OCH2(CHOH)4â€”CH2OH, â€”OCH2(CHOH)2â€”CH2OH, â€”COâ€”OCH2(CHOH)4â€”CH2OH, â€”C6H3(OH)2, â€”N(CH2CO2 H)2, â€”COâ€”N(CH2CO2H)2, â€”COâ€”NHâ€”C(CH2CH2CO2H)3, â€”COâ€”NHâ€”C(CH2CH2OH)3, â€”[CH2 â€”CH(CO2Ra)]1-100â€”H, â€”NH3+, â€”N+H2Ra, â€”N+HRaRb, or â€”N+RaRb Rc, each of Ra, Rb, and Rc, independently, being C1-20 alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30; each of R1 and R4, independently, is &boxH;O or C1-20 hydrocarbon; and each of R2 and R5, independently, is C1-20 hydrocarbon; wherein R1 and R2, or R4 and R5 can join together to form C6-40 aryl which is optionally substituted with halide, â€”OH, â€”NHNH2, â€”NH2OH, â€”NHâ€”CH2â€”CO2H, â€”CH2â€”CH2-D, â€”CH2â€”Bâ€”Z, â€”COâ€”CH2-D, -COâ€”Bâ€”Z, â€”Oâ€”Bâ€”Z, or â€”NHâ€”Bâ€”Z; each of B, D, and Z having been defined above; each of R3 and R6, independently, is â€”H, â€”CH2-D, â€”Bâ€”Z, -G-E, G-CO-E or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E1, E2, or E3, in which E1 is Y1, Y2-amino, (Y1, Y2-alkyl)-amino, Y1, Y2-ethylenediamino, (dihydroxymethyl)alkylamino, (X1, X3-aryl)amino, or X1, X3-aryloxy; E2 is Y1, Y2-alkoxy, (Y1, Y2-amino)alkoxy, (Y1, Y2, Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1, Y2, Y3-alkyl)amino, (Y1, Y2, Y3-aryl)amino, dihydroxyalkylamino, Y1, Y2, Y3-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1, Y2, Y3-alkyl)thio, (X1, X3-aryl)thio, (Y1, Y2-alkyl)thio, (dihydroxyalkyl)thio, Y1, Y2-dioxoalkyl, or tri-(Y1, Y2, Y3-methylaminocarboxyethyl)methylamino; and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1, X2, X3-heteroaryl)amino, (X1-diarylketone)amino, (X1, X1-oxoaryl)amino, (X1, X1-dioxoaryl)amino, (Y1-alkyl, Y2-alkyldioxoheteroaryl)amino, (Y1-alkyl, Y2-alkyldioxoaryl)amino, (di(Y1, Y2-methyl)dioxoheteroaryl) amino, (di(Y1, Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1, X2, X3-alkylaryl)amino, (X1, X2, X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1, X2, X3-oxoheteroaryl)oxy, (X1, X2, X3-oxoaryl)oxy, (X1, Y1-oxoheteroaryl)oxy, (X1-diarylketone)oxy, (X1, X1-oxoaryl)oxy, (X1, X2-dioxoaryl)oxy, (Y1, Y2, di-aminodihydroxy)alkyl, (X1, X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1, X2-oxoaryl)thio, (X1, X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y1-alkyl(thiocarbonyl)thio, Y1, Y2,-alkyl(thiocarbonyl)thio, Y1, Y2, Y3-alkyl(thiocarbonyl)thio, (Y1, Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-100amino, (pyranosyl)amino, (Y1-aminoaryl)1-100amino, (amino(sulfoaryl))1-100amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy; wherein X is halide; each of X1, X2, and X3, independently, is â€”Y1, â€”Oâ€”Y1, â€”Sâ€”Y1, â€”NHâ€”Y1, â€”COâ€”Oâ€”Y1, â€”Oâ€”COâ€”Y1, â€”COâ€”NHâ€”Y1, â€”COâ€”NY1, Y2, â€”NHâ€”COâ€”Y1, â€”SO2â€”Y1, â€”CHY1Y2, or â€”NY1Y2; and each of Y1, Y2, and Y3, independently, is â€”Z or â€”Bâ€”Z; B and Z having been defined above; R7 is â€”Rd or â€”Oâ€”Re; wherein Rd is â€”OH, â€”OM, â€”NHNH2, â€”NHOH, â€”NHâ€”CH2â€”CO2H, â€”Oâ€”Bâ€”Z, â€”NHâ€”Bâ€”Z, -E, â€”O-G-E, â€”NH-G-E, â€”O-G-CO-E, or â€”NH-G-CO-E; M being Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; and Re is â€”H, â€”CH2â€”CH2-D, â€”CH2â€”Bâ€”Z, â€”CH2-G-E, â€”CH2-G-CO-E, â€”COâ€”CH2-D, â€”COâ€”Bâ€”Z, â€”CO-G-E, or â€”CO-G-CO-E; each of B, D, E, G, and Z having been defined above; R8 is Re, which has the same meaning as set forth above; R9 is â€”Oâ€”Rfâ€” or â€”Rgâ€”; wherein Rf is â€”COâ€”B-G-Oâ€”, â€”COâ€”B-G-NHâ€”, â€”COâ€”-B-G-COâ€”Oâ€”, or â€”COâ€”B-G-COâ€”NHâ€”; and Rg is â€”NHâ€”, â€”Oâ€”, â€”Oâ€”B-G-Oâ€”, â€”NHâ€”B-G-Oâ€”, â€”NHâ€”B-G-NHâ€”, â€”Oâ€”COâ€”B-G-COâ€”Oâ€”, or â€”NHâ€”COâ€”B-G-COâ€”NHâ€”; B and G having been defined above; R10 is â€”H; each of x and y, independently, is 0 or 1; and r is 1-100; provided that when x is 0, R1 is &boxH;O, and R7 is â€”Rd; that when y is 0, R4 is &boxH;O, and R9 is â€”R8, and R10 is â€”H; that when x is 1, R1 and R2 join together to form C6-40 aryl, and R7 is â€”Oâ€”Re; and that when y is 1, R4 and R5 join together to form C66-40 aryl, R9 is â€”Oâ€”Rf, and R10 is â€”H; and further provided that when r is greater than 1, x is 0; or a salt thereof.