Heterocyclic aromatic compounds useful as growth hormone secretagogues

1. A compound of the formula I

wherein

R 1 is a substituted or unsubstituted;

R 2 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 hetercycloalkyl;

R 3 and R 4 are each independently a substituted or unsubstituted functional group selected from the group consisting of hydrogen and alkyl, or R 3 and R 4 taken together can form a 4 to 7 membered heterocyclic ring, or one or more of R 3 and R 4 can be taken together with Y to form a 4 to 7 heterocyclic ring;

R 1 ′ 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, —OR 5 , —OC(O)R 5 , —CF 3 , —OCF 3 , —N(R 5 )C(O)R 5 ′ and —NR 5 R 5 ′;

R 5 and R 5 ′ for each occurrence are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle and aryl, wherein R 5 and R 5 ′ for each occurrence may optionally be substituted with one or more Rb;

Rb is 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, —OR 2 , —NR 5 R 5 ′, —CF 3 , —SO 2 R 6 , —OC(O)R 5 —SO 2 NR 6 R 6 ′, —(CH 2 ) m R 8 and R 9 ;

R 6 and R 6 ′ 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 R 6 and R 6 ′ for each occurance may optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, OR 2 , alkoxy, heterocycloalkyl, —NR 5 C(O)NR 5 R 5 ′, —C(O)NR 5 R 5 ′, —NR 5 C(O)R 5 ′, —CN, —NR 5 SO 2 R 5 ′, —OC(O)R 5 , —SO 2 NR 5 R 5 ′, —SOR 7 , —COOH and —C(O)OR 7 , or R 6 and R 6 ′ taken together can be cyclized to form —(CH 2 ) q X(CH 2 ) s —;

R 7 for each occurrence is independently selected from the group consisting of C 1 to C 6 alkyl, aryl and heteroaryl, wherein R 7 may optionally be substituted with —(CH 2 ) w OH;

R 8 is selected from the group consisting of alkoxy, alkoxycarbonyl, —C(O)NR 6 R 6 ′, —NR 5 R 5 ′, —C(O)R 6 , —NR 5 C(O)NR 5 R 5 ′ and —N-heteroaryl;

R 9 is selected from the group consisting of heterocycloalkyl, heteroaryl, —CN, —(CH 2 ) p N(R 6 )C(O)R 6 ′, —(CH 2 ) p CN, —(CH 2 ) p N(R 6 )C(O)OR 6 ′, —(CH 2 ) p N(R 6 )C(O)NR 6 R 6 ′, —(CH 2 ) p N(R 6 )SO 2 R 6 , —(CH 2 ) p C(O)NR 6 R 6 ′, —(CH 2 ) p C(O)OR 6 , —(CH 2 ) p OC(O)OR 6 , —(CH 2 ) p OC(O)R 6 , —(CH 2 ) p OC(O)NR 6 R 6 ′, —(CH 2 ) p N(R 6 )SO 2 NR 6 R 6 ′, —(CH 2 ) p OR 6 , —(CH 2 ) p OC(O)N(R 6 )(CH 2 ) m OH, —(CH 2 ) p SOR 6 and —(CH 2 ) p OCH 2 C(O)N(R 6 )(CH 2 ) m OH;

X is selected from the group consisting of —CR 5 R 5 ′—, —O—, —S—, —SO—, —SO 2 —, —NC(O)OR 7 —, —NC(O)NR 5 — and —NR 5 —;

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 R 5 , R 5 ′, R 6 or R 6 ′ cannot be hydrogen when either is connected to a carbonyl group or sulfone group.

2. The compound as defined in claim 1 wherein when Rb is R 9 , R 6 is heterocycle or alkyl, optionally substituted with hydroxyl or halogen.

3. The compound as defined in claim 2 wherein R 9 is (CH 2 ) p C(O)OR 6 , (CH 2 ) p OC(O)R 6 , or (CH 2 ) p OC(O)N(R 6 )(CH 2 ) m OH.

4. The compound as defined in claim 1 wherein when Rb is R 9 , R 6 and R 6 ′ are independently hydrogen, alkyl, or cycloalkyl, where the alkyl or cycloalkyl is optionally substituted with —C(O)OR 7 or —C(O)NR 5 R 5 ′, or R 6 and R 6 ′ taken together can be cyclized to form —(CH 2 ) q X(CH 2 ) s —.

5. The compound as defined in claim 4 wherein R 9 is —(CH 2 ) p N(R 6 )C(O)OR 6 ′, —(CH 2 ) p N(R 6 )C(O)NR 6 R 6 ′, or (CH 2 ) p OC(O)N R 6 R 6 ′, where R 6 and R 6 ′ are independently hydrogen or alkyl, where the alkyl is optionally substituted with —C(O)NR 5 R 5 ′, where R 5 and R 5 ′ are independently hydrogen or alkyl.

6. The compound as defined in claim 1 wherein the compound has the structure:

7. The compound as defined in claim 1 wherein the compound has the structure:

8. A pharmaceutical composition comprising a compound as defined in claim 1 and a pharmaceutically acceptable carrier therefor.

9. The compound according to claim 1 wherein the compound has the structure

10. The compound according to claim 1 wherein the compound has the structure

11. The compound according to claim 1 wherein the compound has the structure

12. The compound according to claim 1 wherein the compound has the structure