Heterocyclic Aromatic Compounds Useful As Growth Hormone Secretagogues

A method for stimulating wound healing and/or the immune system which comprises administering a therapeutically effective amount of a compound according to Formula I to a patient in need thereof

• wherein
• R1 is a substituted or unsubstituted alkyl;
• R2 is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heterocycle, alkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl and heterocycloalkyl;
• R3 and R4 are each independently a substituted or unsubstituted functional group selected from the group consisting of hydrogen and alkyl, or R3 and R4 taken together can form a 4 to 7 membered heterocyclic ring, or one or more of R3 and R4 can be taken together with Y to form a 4 to 7 membered heterocyclic ring;
• R1′ is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle, aryl and heteroaryl;
• Y is a linking group selected from the group consisting of alkylene, alkenylene, alkynylene, arylene and heteroarylene, said linking group may optionally be substituted with one or more functional group selected from the group consisting of alkyl, aryl, cycloalkyl, heterocycle, alkoxyalkyl, heteroaryl, arylalkyl, arylalkyloxyalkyl, aryloxyalkyl, cycloalkylalkoxyalkyl, heteroarylalkyl, —OR5, —OC(O)R5, —CF3, —OCF3, —N(R5)C(O)R5′ and —NR5R5′;
• R5 and R5′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle and aryl, wherein R5 and R5′ for each occurrence may optionally be substituted with one or more Rb;
• Rb for each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, —CN, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, heterocycle, heteroaryl, heteroarylalkyl, —OR2, —NR5R5′, —CF3, —SO2R6, —OC(O)R5, —SO2NR6R6′, —(CH2)mR8 and R9;
• R6 and R6′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylthioalkyl, alkoxyalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl, heterocycloalkyl and cycloalkyl, wherein R6 and R6′ for each occurrence may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —SOR7, —COOH and —C(O)OR7, or R6 and R6′ taken together can be cyclized to form —(CH2)qX(CH2)s—, which may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5, R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —SOR7′, —COOH and —C(O)OR7;
• R7 for each occurrence is independently selected from the group consisting of C1 to C6 alkyl, aryl and heteroaryl, wherein R7 may optionally be substituted with —(CH2)wOH;
• R8 is selected from the group consisting of alkoxy, alkoxycarbonyl, —C(O)NR6R6′, —NR5R5′, —C(O)R6, —NR5C(O)NR5R5′ and —N-heteroaryl;
• R9 is selected from the group consisting of heterocycloalkyl, heteroaryl, —CN, —(CH2)pN(R6)C(O)R6′, —(CH2)pCN, —(CH2)pN(R6)C(O)OR6′, —(CH2)pN(R6)C(O)NR6R6′, —(CH2)pN(R6)SO2R6, —(CH2)pC(O)NR6R6′, —(CH2)pC(O)OR6, —(CH2)pOC(O)OR6, —(CH2)pOC(O)R6, —(CH2)pOC(O)NR6R6′, —(CH2)pN(R6)SO2NR6R6′, —(CH2)pOR6, —(CH2)pOC(O)N(R6)(CH2)mOH, —(CH2)pSOR6 and —(CH2)pOCH2C(O)N(R6)(CH2)mOH;
• X is selected from the group consisting of —CR5R5′—, —O—, —S—, —SO—, —SO2—, —NC(O)OR7—, —NC(O)NR5— and —NR5—;
• m is an integer between 1 and 6;
• p is an integer from 0 to 5;
• w is an integer between 0 and 5;
• and
• q and s are each independently an integer between 1 and 3,
• with the proviso that R5, R5′, R6 or R6′ cannot be hydrogen when either is connected to a carbonyl group or sulfone group.

A method for increasing muscle mass and/or strength or maintaining muscle strength and function in the elderly which comprises administering a therapeutically effective amount of a compound according to Formula I to a patient in need thereof

• wherein
• R1 is a substituted or unsubstituted alkyl;
• R2 is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heterocycle, alkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl and heterocycloalkyl;
• R3 and R4 are each independently a substituted or unsubstituted functional group selected from the group consisting of hydrogen and alkyl, or R3 and R4 taken together can form a 4 to 7 membered heterocyclic ring, or one or more of R3 and R4 can be taken together with Y to form a 4 to 7 membered heterocyclic ring;
• R1′ is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle, aryl and heteroaryl;
• Y is a linking group selected from the group consisting of alkylene, alkenylene, alkynylene, arylene and heteroarylene, said linking group may optionally be substituted with one or more functional group selected from the group consisting of alkyl, aryl, cycloalkyl, heterocycle, alkoxyalkyl, heteroaryl, arylalkyl, arylalkyloxyalkyl, aryloxyalkyl, cycloalkylalkoxyalkyl, heteroarylalkyl, —OR5, —OC(O)R5, —CF3, —OCF3, —N(R5)C(O)R5′ and —NR5R5′;
• R5 and R5′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle and aryl, wherein R5 and R5′ for each occurrence may optionally be substituted with one or more Rb;
• Rb for each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, —CN, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, heterocycle, heteroaryl, heteroarylalkyl, —OR2, —NR5R5′, —CF3, —SO2R6, —OC(O)R5, —SO2NR6R6′, —(CH2)mR8 and R9;
• R6 and R6′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylthioalkyl, alkoxyalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl, heterocycloalkyl and cycloalkyl, wherein R6 and R6′ for each occurrence may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —COOH and —C(O)OR7, or R6 and R6′ taken together can be cyclized to form —(CH2)qX(CH2)5—, which may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5, R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5′, —SO2NR5R5′, —SOR7′, —COOH and —C(O)OR7;
• R7 for each occurrence is independently selected from the group consisting of C1 to C6 alkyl, aryl and heteroaryl, wherein R7 may optionally be substituted with —(CH2)wOH;
• R8 is selected from the group consisting of alkoxy, alkoxycarbonyl, —C(O)NR6R6′, —NR5R5′, —C(O)R6, —NR5C(O)NR5R5′ and —N-heteroaryl;
• R9 is selected from the group consisting of heterocycloalkyl, heteroaryl, —CN, —(CH2)pN(R6)C(O)R6′, —(CH2)pCN, —(CH2)pN(R6)C(O)OR6′, —(CH2)pN(R6)C(O)NR6R6′, —(CH2)pN(R6)SO2R6, —(CH2)pC(O)NR6R6′, —(CH2)pC(O)OR6, —(CH2)pOC(O)OR6, —(CH2)pOC(O)R6, —(CH2)pOC(O)NR6R6′, —(CH2)pN(R6)SO2NR6R6′, —(CH2)pOR6, —(CH2)pOC(O)N(R6)(CH2)mOH, —(CH2)pSOR6 and —(CH2)pOCH2C(O)N(R6)(CH2)mOH;
• X is selected from the group consisting of —CR5R5′—, —O—, —S—, —SO2—, —NC(O)OR7—, —NC(O)NR5— and —NR5—;
• m is an integer between 1 and 6;
• p is an integer from 0 to 5;
• w is an integer between 0 and 5;
• and
• q and s are each independently an integer between 1 and 3,
• with the proviso that R5, R5′, R6 or R6′ cannot be hydrogen when either is connected to a carbonyl group or sulfone group.

A method of increasing lean body mass which comprises administering a therapeutically effective amount of a compound according to Formula Ito a patient in need thereof

• wherein
• R1 is a substituted or unsubstituted alkyl;
• R2 is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, allynyl, arylalkyl, cycloalkyl, heterocycle, alkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl and heterocycloalkyl;
• R3 and R4 are each independently a substituted or unsubstituted functional group selected from the group consisting of hydrogen and alkyl, or R3 and R4 taken together can form a 4 to 7 membered heterocyclic ring, or one or more of R3 and R4 can be taken together with Y to form a 4 to 7 membered heterocyclic ring;
• R1′ is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle, aryl and heteroaryl;
• Y is a linking group selected from the group consisting of alkylene, alkenylene, alkynylene, arylene and heteroarylene, said linking group may optionally be substituted with one or more functional group selected from the group consisting of alkyl, aryl, cycloalkyl, heterocycle, alkoxyalkyl, heteroaryl, arylalkyl, arylalkyloxyalkyl, aryloxyalkyl, cycloalkylalkoxyalkyl, heteroarylalkyl, —OR5, —OC(O)R5, —CF3, —OCF3, —N(R5)C(O)R5′ and —NR5R5′;
• R5 and R5′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle and aryl, wherein R5 and R5′ for each occurrence may optionally be substituted with one or more Rb;
• Rb for each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, —CN, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, heterocycle, heteroaryl, heteroarylalkyl, —OR2, —NR5R5′, —CF3, —SO2R6, —OC(O)R5, —SO2NR6R6′, —(CH2)mR8 and R9;
• R6 and R6′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylthioalkyl, alkoxyalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl, heterocycloalkyl and cycloalkyl, wherein R6 and R6′ for each occurrence may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —COOH and —C(O)OR7, or R6 and R6′ taken together can be cyclized to form —(CH2)qX(CH2)8—, which may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5, R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5′, —SO2NR5R5′, —SOR7′, —COOH and —C(O)OR7;
• R7 for each occurrence is independently selected from the group consisting of C1 to C6 alkyl, aryl and heteroaryl, wherein R7 may optionally be substituted with —(CH2)wOH;
• R8 is selected from the group consisting of alkoxy, alkoxycarbonyl, —C(O)NR6R6′, —NR5R5′, —C(O)R6, —NR5C(O)NR5R5′ and —N-heteroaryl;
• R9 is selected from the group consisting of heterocycloalkyl, heteroaryl, —CN, —(CH2)pN(R6)C(O)R6′, —(CH2)pCN, —(CH2)pN(R6)C(O)OR6′, —(CH2)pN(R6)C(O)NR6R6′, —(CH2)pN(R6)SO2R6, —(CH2)pC(O)NR6R6′, —(CH2)pC(O)OR6, —(CH2)pOC(O)OR6, —(CH2)pOC(O)R6, —(CH2)pOC(O)NR6R6′, —(CH2)pN(R6)SO2NR6R6′, —(CH2)pOR6, —(CH2)pOC(O)N(R6)(CH2)mOH, —(CH2)pSOR6 and —(CH2)pOCH2C(O)N(R6)(CH2)mOH;
• X is selected from the group consisting of —CR5R5′—, —O—, —S—, —SO—, —SO2—, —NC(O)OR7—, —NC(O)NR5— and —NR5—;
• m is an integer between 1 and 6;
• p is an integer from 0 to 5;
• w is an integer between 0 and 5;
• and
• q and s are each independently an integer between 1 and 3,
• with the proviso that R5, R5′, R6 or R6′ cannot be hydrogen when either is connected to a carbonyl group or sulfone group.

A method for improving cognitive function which comprises administering a therapeutically effective amount of a compound according to Formula Ito a patient in need thereof

• wherein
• R1 is a substituted or unsubstituted alkyl;
• R2 is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heterocycle, alkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl and heterocycloalkyl;
• R3 and R4 are each independently a substituted or unsubstituted functional group selected from the group consisting of hydrogen and alkyl, or R3 and R4 taken together can form a 4 to 7 membered heterocyclic ring, or one or more of R3 and R4 can be taken together with Y to form a 4 to 7 membered heterocyclic ring;
• R1′ is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle, aryl and heteroaryl;
• Y is a linking group selected from the group consisting of alkylene, alkenylene, alkynylene, arylene and heteroarylene, said linking group may optionally be substituted with one or more functional group selected from the group consisting of alkyl, aryl, cycloalkyl, heterocycle, alkoxyalkyl, heteroaryl, arylalkyl, arylalkyloxyalkyl, aryloxyalkyl, cycloalkylalkoxyalkyl, heteroarylalkyl, —OR5, —OC(O)R5, —CF3, —OCF3, —N(R5)C(O)R5′ and —NR5R5′;
• R5 and R5′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle and aryl, wherein R5 and R5′ for each occurrence may optionally be substituted with one or more Rb;
• Rb for each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, —CN, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, heterocycle, heteroaryl, heteroarylalkyl, —OR2, —NR5R5′, —CF3, —SO2R6, —OC(O)R5—(CH2)nR8 and R9;
• R6 and R6′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylthioalkyl, alkoxyalkyl, aryl;
• arylalkyl, heterocycle, heteroaryl, heteroarylalkyl, heterocycloalkyl and cycloalkyl, wherein R6 and R6′ for each occurrence may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —COOH and —C(O)OR7, or R6 and R6′ taken together can be cyclized to form —(CH2)qX(CH2)s—, which may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5, R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —SORT, —COOH and —C(O)OR7;
• R7 for each occurrence is independently selected from the group consisting of C1 to C6 alkyl, aryl and heteroaryl, wherein R7 may optionally be substituted with —(CH2)wOH;
• R8 is selected from the group consisting of alkoxy, alkoxycarbonyl, —C(O)NR6R6′, —NR5R5′, —C(O)R6, —NR5C(O)NR5R5′ and —N-heteroaryl;
• R9 is selected from the group consisting of heterocycloalkyl, heteroaryl, —CN, —(CH2)pN(R6)C(O)R6′, —(CH2)pCN, —(CH2)pN(R6)C(O)OR6′, —(CH2)pN(R6)C(O)NR6R6′, —(CH2)pN(R6)SO2R6, —(CH2)pC(O)NR6R6′, —(CH2)pC(O)OR6, —(CH2)pOC(O)OR6, —(CH2)pOC(O)R6, —(CH2)pOC(O)NR6R6′, —(CH2)pN(R6)SO2NR6R6′, —(CH2)pOR6, —(CH2)pOC(O)N(R6)(CH2)mOH, —(CH2)pSOR6 and —(CH2)pOCH2C(O)N(R6)(CH2)mOH;
• X is selected from the group consisting of —CR5R5′—, —O—, —S—, —SO2—, —NC(O)OR7—, —NC(O)NR5— and —NR5—;
• m is an integer between 1 and 6;
• p is an integer from 0 to 5;
• w is an integer between 0 and 5;
• and
• q and s are each independently an integer between 1 and 3,
• with the proviso that R5, R5′, R6 or R6′ cannot be hydrogen when either is connected to a carbonyl group or sulfone group.

A method for improving the immune response to vaccination which comprises administering a therapeutically effective amount of a compound according to Formula Ito a patient in need thereof.

• wherein
• R1 is a substituted or unsubstituted alkyl;
• R2 is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heterocycle, alkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl and heterocycloalkyl;
• R3 and R4 are each independently a substituted or unsubstituted functional group selected from the group consisting of hydrogen and alkyl, or R3 and R4 taken together can form a 4 to 7 membered heterocyclic ring, or one or more of R3 and R4 can be taken together with Y to form a 4 to 7 membered heterocyclic ring;
• R1′ is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle, aryl and heteroaryl;
• Y is a linking group selected from the group consisting of alkylene, alkenylene, alkynylene, arylene and heteroarylene, said linking group may optionally be substituted with one or more functional group selected from the group consisting of alkyl, aryl, cycloalkyl, heterocycle, alkoxyalkyl, heteroaryl, arylalkyl, arylalkyloxyalkyl, aryloxyalkyl, cycloalkylalkoxyalkyl, heteroarylalkyl, —OR5, —OC(O)R5, —CF3, —OCF3, —N(R5)C(O)R5′ and —NR5R5′;
• R5 and R5′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle and aryl, wherein R5 and R5′ for each occurrence may optionally be substituted with one or more Rb;
• Rb for each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, —CN, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, heterocycle, heteroaryl, heteroarylalkyl, —OR2, —NR5R5′, —CF3, —SO2R6, —OC(O)R5, —SO2NR6R6′, —(CH2)mR8 and R9;
• R6 and R6′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylthioalkyl, alkoxyalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl, heterocycloalkyl and cycloalkyl, wherein R6 and R6′ for each occurrence may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —SOR7, —COOH and —C(O)OR7, or R6 and R6′ taken together can be cyclized to form —(CH2)qX(CH2)s—, which may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5, R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —SOR7′, —COOH and —C(O)OR7;
• R7 for each occurrence is independently selected from the group consisting of C1 to C6 alkyl, aryl and heteroaryl, wherein R7 may optionally be substituted with —(CH2)wOH;
• R8 is selected from the group consisting of alkoxy, alkoxycarbonyl, —C(O)NR6R6′, —C(O)R6, —NR5C(O)NR5R5′ and —N-heteroaryl;
• R9 is selected from the group consisting of heterocycloalkyl, heteroaryl, —CN, —(CH2)pN(R6)C(O)R6′, —(CH2)pCN, —(CH2)pN(R6)C(O)OR6′, —(CH2)pN(R6)C(O)NR6R6′, —(CH2)pN(R6)SO2R6, —(CH2)pC(O)NR6R6′, —(CH2)pC(O)OR6, —(CH2)pOC(O)OR6, —(CH2)pOC(O)R6, —(CH2)pOC(O)NR6R6′, —(CH2)pN(R6)SO2NR6R6′, —(CH2)pOR6, —(CH2)pOC(O)N(R6)(CH2)mOH, —(CH2)pSOR6 and —(CH2)pOCH2C(O)N(R6)(CH2)mOH;
• X is selected from the group consisting of —CR5R5′—, —O—, —S—, —SO—, —SO2—, —NC(O)OR7—, —NC(O)NR5— and —NR5—;
• m is an integer between 1 and 6;
• p is an integer from 0 to 5;
• w is an integer between 0 and 5;
• and
• q and s are each independently an integer between 1 and 3,
• with the proviso that R5, R5′, R6 or R6′ cannot be hydrogen when either is connected to a carbonyl group or sulfone group.

A method for accelerating the recovery of hip fracture which comprises administering a therapeutically effective amount of a compound according to Formula Ito a patient in need thereof

• wherein
• R1 is a substituted or unsubstituted alkyl;
• R2 is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heterocycle, alkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, heteroaryl, cycloalkylalkoxyalkyl, heteroarylalkyl and heterocycloalkyl;
• R3 and R4 are each independently a substituted or unsubstituted functional group selected from the group consisting of hydrogen and alkyl, or R3 and R4 taken together can form a 4 to 7 membered heterocyclic ring, or one or more of R3 and R4 can be taken together with Y to form a 4 to 7 membered heterocyclic ring;
• R1′ is a substituted or unsubstituted functional group selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle, aryl and heteroaryl;
• Y is a linking group selected from the group consisting of alkylene, alkenylene, alkynylene, arylene and heteroarylene, said linking group may optionally be substituted with one or more functional group selected from the group consisting of alkyl, aryl, cycloalkyl, heterocycle, alkoxyalkyl, heteroaryl, arylalkyl, arylalkyloxyalkyl, aryloxyalkyl, cycloalkylalkoxyalkyl, heteroarylalkyl, —OR5, —OC(O)R5, —CF3, —OCF3, —N(R5)C(O)R5′ and —NR5R5′;
• R5 and R5′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle and aryl, wherein R5 and R5′ for each occurrence may optionally be substituted with one or more Rb;
• Rb for each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, —CN, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, heterocycle, heteroaryl, heteroarylalkyl, —OR2, —NR5R5′, —CF3, —SO2R6, —OC(O)R5, —SO2NR6R6′, —(CH2)mR8 and R9;
• R6 and R6 for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylthioalkyl, alkoxyalkyl, aryl, arylalkyl, heterocycle, heteroaryl, heteroarylalkyl, heterocycloalkyl and cycloalkyl, wherein R6 and R6′ for each occurrence may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5, —SO2NR5R5′, —SOR7, —COOH and —C(O)OR7, or R6 and R6′ taken together can be cyclized to form —(CH2)qX(CH2)s—, which may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR2, alkoxy, heterocycloalkyl, —NR5C(O)NR5R5′, —C(O)NR5, R5′, —NR5C(O)R5′, —CN, —NR5SO2R5′, —OC(O)R5′, —SO2NR5R5′, —SOR7′, —COOH and —C(O)OR2;
• R7 for each occurrence is independently selected from the group consisting of C1 to C6 alkyl, aryl and heteroaryl, wherein R7 may optionally be substituted with —(CH2)wOH;
• R8 is selected from the group consisting of alkoxy, alkoxycarbonyl, —C(O)NR6R6′, —NR5R5′, —C(O)R6, —NR5C(O)NR5R5′ and —N-heteroaryl;
• R9 is selected from the group consisting of heterocycloalkyl, heteroaryl, —CN, —(CH2)pN(R6)C(O)R6′, —(CH2)pCN, —(CH2)pN(R6)C(O)OR6′, —(CH2)pN(R6)C(O)NR6R6′, —(CH2)pN(R6)SO2R6, —(CH2)pC(O)NR6R6′, —(CH2)pC(O)OR6, —(CH2)pOC(O)OR6, —(CH2)pOC(O)R6, —(CH2)pOC(O)NR6R6′, —(CH2)pN(R5)SO2NR6R6′, —(CH2)pOR6, —(CH2)pOC(O)N(R6)(CH2)mOH, —(CHOpSOR6 and —(CH2)pOCH2C(O)N(R6)(CH2)mOH;
• X is selected from the group consisting of —CR5R5′—, —O—, —S—, —SO—, —SO2—, —NC(O)OR7—, —NC(O)NR5— and —NR5—;
• m is an integer between 1 and 6;
• p is an integer from 0 to 5;
• w is an integer between 0 and 5;
• and
• q and s are each independently an integer between 1 and 3,
• with the proviso that R5, R5′, R6 or R6′ cannot be hydrogen when either is connected to a carbonyl group or sulfone group.