Heterocyclic aromatic compounds useful as growth hormone secretagogues

1. A compound according to Formula I, including pharmaceutically acceptable salts thereof, prodrug esters thereof and all stereoisomers thereof:

wherein,

R 1 is selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, arylalkoxyalkyl, aryloxyalkyl and cycloalkylalkoxyalkyl, wherein these groups may optionally be substituted by 1-3 substituents selected from the group consisting of halogen, —OR 8 , —OC(O)R 8 , alkyl, phenyl, phenoxy, halophenyl, —CF 3 , —OCF 3 , —N(R 8a )C(O)(R 8 ) and —N(R 8 )(R 8a );

R 1a is selected from the group consisting of hydrogen, alkyl and cycloalkyl;

Z is selected from the group consisting of a direct bond and —S—;

R 5 is selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxyalkyl, cycloalkylalkoxyalkyl, —SO 2 T 1 , —SO 2 (T 1a )T 1 ,

wherein, alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxyalkyl and cycloalkylalkoxyalkyl may be substituted with 1-3 J 1 ;

R 5a is selected from the group consisting of hydrogen, alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxyalkyl, cycloalkylalkoxyalkyl, J 1 ,

wherein, alkyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkyl, arylalkynyl, cycloalkylalkyl, alkoxyalkyl, aryloxyalkyl, arylalkyloxyalkyl and cycloalkylalkoxyalkyl may be substituted with 1-3 J 1 ;

Y is selected from the group consisting of

where x and y are 0-3 and z is 1-3;

X c is selected from the group consisting of a direct bond, —N(R 6a ) and —O—;

R 7 and R 7a are selected from the group consisting of hydrogen, alkyl, —CF 3 , phenyl, aryl, arylalkyl and cycloalkyl, wherein one or both of R 7 and R 7a can be independently joined to one or both of R 9 and R 10 to form an alkylene bridge of 1 to 5 carbon atoms or R 7 and R 7a may be taken together to form a ring of 3-7 carbon atoms;

R 6 , R 6a , R 8 , R 8a , R 8d , R 8e , R 8f , R 8g and R 8i are selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl and aryl;

R 9 and R 10 are selected from the group consisting of hydrogen, alkyl and substituted alkyl, wherein the substitutents are selected from the group consisting of 1-3 hydroxyls, 1-3 C 1 -C 10 -alkanoyloxy, 1-3 C 1 -C 6 -alkoxy, phenyl, phenoxy and C 1 -C 6 -alkoxycarbonyl;

J 1 is selected from the group consisting of nitro, —(CH 2 ) v N(T 1a )C(O)T 1 , —(CH 2 ) v CN, —(CH 2 ) v N(T 1a )C(O)OT 1 , —(CH 2 ) v N(T 1a )C(O)N(T 1b )T 1 , —(CH 2 ) v N(T 1a )SO 2 T 1 , —(CH 2 ) v C(O)N(T 1a )T 1 , —(CH 2 ) v C(O)OT 1 , —(CH 2 ) v OC(O)OT 1 , —(CH 2 ) v OC(O)T 1 , —(CH 2 ) v OC(O)N(T 1a )T 1 , —(CH 2 ) v N(T 1a )SO 2 N(T 1b )T 1 , —(CH 2 ) v OT 1 , —(CH 2 ) v SO 2 T 1 , —(CH 2 ) v SO 2 N(T 1a )T 1 , —(CH 2 ) v C(O)T 1 and —(CH 2 ) v CH(OH)T 1 wherein v is 0-5;

T 1 , T 1a and T 1b are selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, lower alkylthioalkyl, alkoxyalkyl, aryl, arylalkyl, cycloheteroalkyl and cycloalkyl, each of which may be substituted with 1-3 substitutents selected from the group consisting of halogen, hydroxyl, —NR 8f C(O)NR 8g R 8i , —C(O)NR 8f R 8g , —NR 8f C(O)R 8g , —CN, —N(R 8f )SO 2 R 14 , —OC(O)R 8f , SO 2 NR 8f R 8g , —SOR 14 , —SO 2 R 14 , alkoxy, —CO 2 H, cycloheteroalkyl and —C(O)OR 14 , with the proviso that T 1 can not be hydrogen when it is connected to carbonyl or sulfur, as in —C(O)T 1 or —SO 2 T 1 ; and

R 14 is selected from the group consisting of C 1 -C 6 -alkyl, and aryl, wherein each may be substituted with —(CH 2 ) s OH wherein s is 0-5.

2. The compound according to claim 1 , wherein:

R 1 is selected from the group consisting of arylalkyl, arylalkyloxyalkyl and aryloxyalkyl.

3. The compound according to claim 1 , wherein:

R 1a is selected from the group consisting of hydrogen and alkyl.

4. The compound according to claim 1 , wherein:

R 1 is arylalkyloxyalkyl and R 1a is hydrogen.

5. The compound according to claim 1 , wherein:

R 6 is hydrogen.

6. The compound according to claim 4 , wherein:

R 5 is alkyl optionally substituted with 1-3 J 1 ;

R 5a is hydrogen; and

R 6 is selected from the group consisting of alkyl and arylalkyl, wherein the arylalkyl is substituted with 1-3 J 1 .

7. The compound according to claim 1 , wherein:

Y is

wherein,

x and y are 0;

X c is a direct bond; and

R 7 and R 7a are independently alkyl.

8. The compound according to claim 1 , wherein:

R 9 R 10 are independently selected from the group consisting of hydrogen and substituted alkyl, wherein the alkyl is substituted with 1-2 hydroxyls.

9. The compound according to claim 1 , wherein:

J 1 is selected from the group consisting of —(CH 2 ) v CN, —(CH 2 ) v C(O)N(T 1a )T 1 , —(CH 2 ) v N(T 1a )C(O)OT 1 , —(CH 2 ) v OC(O)N(T 1a )T 1 , —(CH 2 ) v N(T 1a )C(O)N(T 1b )T 1 , wherein v is 0-4;

T 1 , T 1a and T 1b are selected from the group consisting of alkyl, lower alkylthioalkyl, alkoxyalkyl, aryl, arylalkyl heteroarylalkyl ande cycloheteroalkyl, each of which may be substituted with —OC(O)R 8f , —C(O)NR 8f R 8g , —SOR 14 and —(CH 2 ) s OH, wherein s is 0-2.

10. The compound according to claim 1 , wherein the compound is selected from the group consisting of:

11. The compound according to claim 1 according to the formula:

X 1 —R

wherein,

X 1 is

and

R is selected from the group consisting of:

12. The compound according to claim 1 having the structure

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition, comprising:

at least one compound according to claim 1 ; and

at least one pharmaceutically acceptable carrier.