Heterocyclic analgesic compounds and methods of use thereof

A composition, comprising:

• an excipient selected from the group consisting of cyclodextrins, liposomes, micelle forming agents, and polymeric carriers;
• and a compound selected from the group consisting of:
• a compound represented by A:
• wherein
• m is 1, 2, 3 or 4;
• n is 1;
• y is 1 or 2;
• R1 represents alkyl;
• monocyclic or polycyclic aryl;
• or cycloalkyl;
• R2 represents independently for each occurrence H;
• alkyl;
• fluoroalkyl;
• aryl;
• or cycloalkyl;
• R1 and R2 may be connected through a covalent bond;
• R3 represents independently for each occurrence H;
• alkyl;
• monocyclic or polycyclic aryl;
• OR2;
• OC(O)R2;
• CH2OR2;
• or CO2R2;
• wherein any two instances of R3 may be connected by a covalent tether whose backbone consists of 1, 2, 3, or 4 carbon atoms;
• R4 represents H;
• alkyl;
• monocyclic or polycyclic aryl;
• alkenyl;
• or cycloalkyl;
• R5 represents independently for each occurrence H;
• alkyl;
• CH2Y;
• monocyclic or polycyclic aryl;
• F;
• OR2;
• or OC(O)R2;
• R6 represents independently for each occurrence H;
• alkyl;
• CH2Y;
• monocyclic or polycyclic aryl;
• F;
• OR2;
• or OC(O)R2;
• Y represents independently for each occurrence OR2, N(R2)2, SR2, S(O)R2, S(O)2R2, or P(O)(OR2)2;
• a covalent bond may connect R4 and an instance of R5 or R6 that is attached to the carbon chain between R4 and the ring nitrogen explicitly shown in A;
• any two geminal or vicinal instances of R5 and R6 may be connected through a covalent bond;
• X represents C(R3)2;
• and
• the stereochemical configuration at any stereocenter of a compound represented by A is R, S, or a mixture of these configurations;
• a compound represented by B:
• wherein
• m is 1, 2, 3 or 4;
• n is 1;
• R1 represents H;
• alkyl;
• monocyclic or polycyclic aryl;
• or cycloalkyl;
• R2 represents independently for each occurrence H;
• alkyl;
• fluoroalkyl;
• monocyclic or polycyclic aryl;
• or cycloalkyl;
• R1 and R2 may be connected through a covalent bond;
• R3 represents independently for each occurrence H;
• alkyl;
• monocyclic or polycyclic aryl;
• OR2;
• OC(O)R2;
• CH2OR2;
• or CO2R2;
• wherein any two instances of R3 may be connected by a covalent tether whose backbone consists of 1, 2, 3, or 4 carbon atoms;
• R4 represents H;
• alkyl;
• monocyclic or polycyclic aryl;
• alkenyl;
• or cycloalkyl;
• R5 represents independently for each occurrence H;
• alkyl;
• CH2Y;
• monocyclic or polycyclic aryl;
• F;
• OR2;
• or OC(O)R2;
• R6 represents independently for each occurrence H;
• alkyl;
• CH2Y;
• monocyclic or polycyclic aryl;
• F;
• OR2;
• or OC(O)R2;
• Y represents independently for each occurrence OR2, N(R2)2, SR2, S(O)R2, S(O)2R2, or P(O)(OR2)2;
• a covalent bond may connect R4 and an instance of R5 or R6 that is attached to the carbon chain between R4 and the ring nitrogen explicitly shown in B;
• any two geminal or vicinal instances of R5 and R6 may be connected through a covalent bond;
• X represents C(R3)2;
• and
• the stereochemical configuration at any stereocenter of a compound represented by B is R or S;
• and
• a compound represented by E:
• wherein
• m is 1, 2, 3 or 4;
• n is 1;
• R1 represents H;
• alkyl;
• monocyclic or polycyclic aryl;
• or cycloalkyl;
• R2 represents independently for each occurrence H;
• alkyl;
• fluoroalkyl;
• monocyclic or polycyclic aryl;
• or cycloalkyl;
• R1 and R2 may be connected through a covalent bond;
• R3 represents independently for each occurrence H;
• alkyl;
• monocyclic or polycyclic aryl;
• OR2;
• OC(O)R2;
• CH2OR2;
• or CO2R2;
• wherein any two instances of R3 may be connected by a covalent tether whose backbone consists of 1, 2, 3, or 4 carbon atoms;
• R4 represents H;
• alkyl;
• monocyclic or polycyclic aryl;
• alkenyl;
• or cycloalkyl;
• R5 represents independently for each occurrence H;
• alkyl;
• CH2Y;
• monocyclic or polycyclic aryl;
• F;
• OR2;
• or OC(O)R2;
• R6 represents independently for each occurrence H;
• alkyl;
• CH2Y;
• monocyclic or polycyclic aryl;
• F;
• OR2;
• or OC(O)R2;
• Y represents independently for each occurrence OR2, N(R2)2, SR2, S(O)R2, S(O)2R2, or P(O)(OR2)2;
• a covalent bond may connect R4 and an instance of R5 or R6 that is attached to the carbon chain between R4 and the ring nitrogen explicitly shown in E;
• any two geminal or vicinal instances of R5 and R6 may be connected through a covalent bond;
• X represents C(R3)2;
• and
• the stereochemical configuration at any stereocenter of a compound represented by E is R, S, or a mixture of these configurations.