Selective Opioid Compounds

A method of preventing or treating a condition or disease associated with binding opioid receptors in a patient in need thereof, comprising the step of:

• administering to said patient a composition comprising an effective amount of a compound of Formula I or II:
• or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein:
• R1 is selected from the group consisting of:
• hydrogen, halogen, ORa, SRa, S(O)Ra, SO2Ra, S(O)NRbRc, SO2NRbRc, NRb-Q-Rc, CN, (C═W)NRbRc, C(O)ORa, CH2ORa, CH2NRbRc, heteroaryl, and substituted heteroaryl;
• Ra, Rb, Rc are each independently selected from:
• (i) hydrogen;
• (ii) aryl;
• substituted aryl;
• heteroaryl;
• substituted heteroaryl;
• (iii) heterocyclic or substituted heterocyclic;
• and
• (iv) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;
• —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkyl;
• —C3-C12 cycloalkenyl, or substituted —C3-C12 cycloalkenyl;
• alternatively, Rb and Rc are taken together to form a heterocyclic or substituted heterocyclic;
• Q is absent or selected from (C═O), (SO2), (C═NH), (C═S), or (CONRa);
• W is O, S, NORa or NRa;
• R2 is independently selected from the group consisting of hydrogen, halogen, ORa, SRa, NRbRc;
• alternatively, R1 and R2 are taken together to form a heteroaryl, substituted heteroaryl, heterocyclic or substituted heterocylic;
• R3 is independently selected from the group consisting of:
• (v) hydrogen;
• (vi) aryl;
• substituted aryl;
• heteroaryl;
• substituted heteroaryl;
• (vii) heterocyclic or substituted heterocyclic;
• and
• (viii) —C1-C8 alkyl, —C2-C8 alkenyl, or —C2-C8 alkynyl each containing 0, 1, 2, or 3 or more heteroatoms selected from O, S, or N;
• substituted —C1-C8 alkyl, substituted —C2-C8 alkenyl, or substituted —C2-C8 alkynyl each containing 0, 1, 2, or 3 or more heteroatoms selected from O, S or N;
• —C3-C12 cycloalkyl, or substituted —C3-C12 cycloalkyl;
• —C3-C12 cycloalkenyl, or substituted —C3-C12 cycloalkenyl;
• R4 is hydrogen, ORa, or NRb-Q1-Rc, where Q1 is absent or selected from (C═O) or (SO2);
• R5 is selected from the group consisting of:
• hydrogen, halogen, SRa, S(O)Ra, SO2Ra, S(O)NRbRc, SO2NRbRc, NRb-Q-Rc, CN, (C═W)NRbRc, C(O)ORa, CH2ORa, CH2NRbRc, heteroaryl, and substituted heteroaryl;
• Y is hydrogen, lower alkyl, or lower alkoxy;
• V1 is C═O, SO2, C1-C6 alkylene, substituted alkylene, C2-C6 alkenylene, C2-C6 alkynylene;
• V2 is absent, alkylene, substituted alkylene, C2-C6 alkenylene, C2-C6 alkynylene;
• heterocyclic, heteroaryl, aryl or C═O;
• V3 is absent, alkylene, substituted alkylene, C2-C6 alkenylene, C2-C6 alkynylene;
• heterocyclic, heteroaryl, aryl or C═O;
• V4 is absent, alkylene, substituted alkylene, C2-C6 alkenylene, C2-C6 alkynylene;
• heterocyclic, heteroaryl, aryl or C═O;
• n is 1, 2, 3 or 4;
• wherein each repeating unit can be the same or different;
• Z is hydrogen, NRbRc, (C═W)NRbRc, NRa(C═W)NRbRc, (C═W)OH, C(O)NHOH, heteroaryl, or substituted heteroaryl;
• alternatively,
• can be selected from the group consisting of natural or unnatural amino acids and peptidomimetics;
• and
• denotes a carbon-carbon single or double bond.