Patent ID: 6392012
Filing Date: 2002-05-21
Classification: A61K,A61P,C07K

Abstract:
A compound of formula I: whereinR1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and â€”Raâ€”Yâ€”Rbâ€”(Z)x; or a saccharide group optionally substituted with â€”Raâ€”Yâ€”Rbâ€”(Z)x; R2 is hydrogen or a saccharide group optionally substituted with â€”Raâ€”Yâ€”Rbâ€”(Z)x; R3 is â€”ORc, â€”NRcRc, â€”Oâ€”Raâ€”Yâ€”Rbâ€”(Z)x, â€”NRcâ€”Raâ€”Yâ€”Rbâ€”(Z)x, â€”NRcRe, or â€”Oâ€”Rc; R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, â€”Raâ€”Yâ€”Rbâ€”(Z)x, â€”C(O)Rd and a saccharide group optionally substituted with â€”Raâ€”Yâ€”Rbâ€”(Z)x; R5 is CH(Rc)â€”NRcâ€”Raâ€”Yâ€”Rbâ€”(Z)x; R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, â€”Raâ€”Yâ€”Rbâ€”(Z)x, C(O)Rd and a saccharide group optionally substituted with â€”NRcâ€”Raâ€”Yâ€”Rbâ€”(Z)x, or R5 and R6 can be joined, together with the atoms to which they are attached, to form a heterocyclic ring optionally substituted with â€”NR6â€”Raâ€”Yâ€”Rbâ€”(Z)x; R7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, â€”Raâ€”Yâ€”Rbâ€”(Z)x, and â€”C(O)Rd; R8 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic; R9 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic; R10 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic; or R8 and R10 are joined to form â€”Ar1â€”Oâ€”Ar2â€”, where Ar1 and Ar2 are independently arylene or heteroarylene; R11 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic, or R10 and R11 are joined, together with the carbon and nitrogen atoms to which they are attached, to form a heterocyclic ring; R12 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, â€”C(O)Rd, â€”C(NH)Rd, â€”C(O)NRcRc, â€”C(O)ORd, â€”C(NH)NRcRc and â€”Raâ€”Yâ€”Rbâ€”(Z)x, or R11 and R12 are joined, together with the nitrogen atom to which they are attached, to form a heterocyclic ring; R13 is selected from the group consisting of hydrogen and â€”OR14; R14 is selected from the group consisting of hydrogen, â€”C(O)Rd and a saccharide group; each Ra is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene; each Rb is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided Rb is not a covalent bond when Z is hydrogen; each Rc is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and â€”C(O)Rd; each Rd is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic; Re is a saccharide group; X1, X2 and X3 are independently selected from the group consisting of hydrogen and chloro; each Y is independently selected from the group consisting of oxygen, sulfur, â€”Sâ€”Sâ€”, â€”NRcâ€”, â€”S(O)â€”, â€”SO2â€”, â€”NRcC(O)â€”, â€”OSO2â€”, â€”OC(O)â€”, â€”NRcSO2â€”, â€”C(O)NRcâ€”, â€”C(O)Oâ€”, â€”SO2NRcâ€”, â€”SO2Oâ€”, â€”P(O)(ORc)Oâ€”, â€”P(O)(ORc)NRcâ€”, â€”OP(O)(ORc)Oâ€”, â€”OP(O)(ORc)NRcâ€”, â€”OC(O)Oâ€”, â€”NRcC(O)Oâ€”, â€”NRcC(O)NRcâ€”, â€”OC(O)NRcâ€” and â€”NRcSO2NRcâ€”; each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic; n is 0, 1 or 2; x is 1 or 2; and pharmaceutically acceptable salts, stereoisomers and prodrugs thereof; and provided that: (i) when Y is â€”NRcâ€”, Rc is alkyl of 1 to 4 carbon atoms, Z is hydrogen and Rb is alkylene, then Rb contains at least 5 carbon atoms; (ii) when Y is â€”C(O)NRcâ€”, Z is hydrogen and Rb is alkylene, then Rb contains at least 5 carbon atoms; (iii) when Y is sulfur, Z is hydrogen and Rb is alkylene, then Rb contains at least 7 carbon atoms; and (iv) when Y is oxygen, Z is hydrogen and Rb is alkylene, then Rb contains at least 11 carbon atoms.