Novel [N-Me-4-hydroxyleucine]-9-Cyclosporin Analogues for Treatment and Prevention of Hepatitis C Infection

A compound represented by the formula (I) or (II):

• or a pharmaceutically acceptable salt, ester or prodrug thereof,
• wherein R1 is selected from:
• a) R11, wherein R11 is selected from:
• 1) Hydrogen;
• 2) Deuterium;
• 3) C1-C8 alkyl;
• 4) Substituted C1-C8 alkyl;
• 5) C2-C8 alkenyl;
• 6) Substituted C2-C8 alkenyl;
• 7) C2-C8 alkynyl;
• 8) Substituted C2-C8 alkynyl;
• 9) C3-C12 cycloalkyl;
• 10) Substituted C3-C12 cycloalkyl;
• 11) Aryl;
• 12) Substituted aryl;
• 13) Heterocycloalkyl;
• 14) Substituted heterocycloalkyl;
• 15) Heteroaryl;
• and
• 16) Substituted heteroaryl;
• b) —C(O)N(R12)(R13), wherein R12 and R13 are independently selected from R11 and R11 is as previously defined or R12 and R13 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocycloalkyl;
• c) R14, wherein R14 is selected from:
• 1)-M-R11, wherein R11 is as previously defined and M is selected from:
• i. C1-C8 alkylene;
• ii. Substituted C1-C8 alkylene;
• iii. C2-C8 alkenylene;
• iv. Substituted C2-C8 alkenylene;
• v. C2-C8 alkynylene;
• vi. Substituted C2-C8 alkynylene;
• vii. C3-C12 cycloalkylene;
• viii. Substituted C3-C12 cycloalkylene;
• 2) -M-NR15R18, wherein R15 and R18 are each independently R11;
• or R15 and R18 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocycloalkyl, and M is as previously defined;
• 3) -M-S(O)mRii, wherein m=0, 1, or 2;
• M and R11 are as previously defined;
• 4) -M-OR11, wherein M and R11 are as previously defined;
• 5) -M-C(O)R16, wherein M is as previously defined and R16 is selected from
• i. C1-C8 alkyl;
• ii. Substituted C1-C8 alkyl;
• iii. C2-C8 alkenyl;
• iv. Substituted C2-C8 alkenyl;
• v. C2-C8 alkynyl;
• vi. Substituted C2-C8 alkynyl;
• vii. C3-C12 cycloalkyl;
• and
• viii. Substituted C3-C12 cycloalkyl;
• 6) -M-OC(O)R16, wherein M and R16 are as previously defined;
• 7) -M-OC(O)OR16, wherein M and R16 are as previously defined;
• 8) -M-NR17C(O)R16, wherein R17 is R11, M and R16 are as previously defined;
• 9) -MNR17C(O)OR16, wherein R17, M and R16 are as previously defined;
• 10) -M-C(O)NR17R11, wherein R17, M and R11 are as previously defined;
• 11) -M-C(O)N(R17)—OR11, wherein R17, M and R11 are as previously defined;
• 12) -M-OC(O)NR17R11, wherein R17, M and R11 are as previously defined;
• 13) -M-NR17C(O)NR16R18, wherein M, R16, R17 and R18 are as previously defined or R16 and R17 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocycloalkyl;
• 14) -M-C(S)SR11, wherein M and R11 are as previously defined;
• 15) -M-OC(S)SR16, wherein M and R16 are as previously defined;
• 16) -M-NR17C(O)SR16, wherein M, R17 and R16 are as previously defined;
• 17) -M-SC(O)NR17R18, wherein M, R18 and R17 are as previously defined or R17 and R18 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocycloalkyl;
• 18) -M-CH═N—OR11, wherein M and R11 are as previously defined;
• 19) -M-CH═N—NR17R18, wherein M, R18 and R17 are as previously defined or R17 and R18 are taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocycloalkyl;
• W is absent, or —O—, or —S(O)m—, where m=0, or 1, or 2;
• R2, R3 and R4 are independently selected from:
• hydrogen or methyl.