Growth hormone secretagogues
The invention relates to compounds of formula I which are useful for elevating the plasma level of growth hormone in a mammal as well as for the treatment of growth hormone secretion deficiency, growth retardation in child and metabolic disorders associated with growth hormone secretion deficiency.
1. Compounds of the formula I
wherein * means a carbon atom which, when a chiral carbon atom, has a R or S configuration, one of R 1 and R 3 is an hydrogen atom and the other is a group of formula II
R 2 is a hydrogen atom, a linear or branched C 1 -C 6 alkyl group, an aryl group, a heterocyclic group, a cycloalkyl group, a (CH 2 ) n -aryl group, a (CH 2 ) n -heterocyclic group, a (CH 2 ) n -cycloalkyl group, a methylsulfonyl group, a phenylsulfonyl group, a C(O)R 8 group or a group according to one of formulas III to VIII:
R 4 is a hydrogen atom or a linear or branched C 1 -C 4 alkyl group, R 5 is a hydrogen atom, a linear or branched C 1 -C 4 alkyl group, a (CH 2 ) n -aryl group, a (CH 2 ) n -heterocyclic group, a (CH 2 ) n -cycloalkyl group or an amino group, R 6 and R 7 are independently from each other a hydrogen atom or a linear or branched C 1 -C 4 -alkyl group, R 8 is a linear or branched C 1 -C 6 -alkyl group, R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 are independently from each other a hydrogen atom or a linear or branched C 1 -C 4 -alkyl group, m is 0, 1 or 2 and n is 1 or 2.
2. Compounds according to claim 1 , wherein R 2 is hydrogen, R 3 is a group of formula II and m is 0.
3. Compounds according to claim 2 , wherein the linear or branched C 1 -C 4 alkyl group is methyl, the linear or branched C 1 -C 6 alkyl group is methyl, ethyl or i-butyl, aryl is phenyl or naphthyl, cycloalkyl is cyclohexyl and the heterocyclic group is a 4-piperidinyl or 3-pyrrolyl group.
4. A compound having the following structure:
5. A pharmaceutical composition, comprising a therapeutically effective amount of the compound of claim 1 .
6. The composition of claim 5 , in combination with a pharmaceutically acceptable carrier.
7. The composition of claim 5 , in combination with an additional growth hormone secretagogue.
8. A method for elevating the plasma level of growth hormone in a mammal comprising administering to a mammal an amount effective of the compound according to claim 1 so as to elevate the plasma level of growth hormone.
9. A method for the treatment of growth hormone secretion deficiency comprising administering to a mammal in need thereof a therapeutically effective amount of the compound according to claim 1 so as to treat the growth hormone secretion deficiency.
10. A method for the treatment of growth retardation in a child in need thereof comprising administering to said child a therapeutically effective amount of the compound according to claim 1 so as to treat the growth retardation.
11. A method for the treatment of metabolic disorders associated with growth hormone secretion deficiency comprising administering to a patient in need thereof a therapeutically effective amount of the compound according to claim 1 so as to treat the metabolic disorder.
12. The method of claim 11 , wherein the patient is elderly.
13. A method for promoting wound healing, or recovery from surgery, which comprises administering a therapeutically effective amount of the compound according to claim 1 so as to promote the healing or recovery.
14. The method of claim 13 , wherein the method comprises promoting wound healing.
15. The method of claim 13 , wherein the method comprises promoting recovery from surgery.
16. The compound of claim 1 , wherein R 5 is the amino group which comprises —NH—CH 2 —CH 3 .
17. The compound of claim 16 , wherein the compound is H-Aib-(D)-Trp-(D)-gTrp-C(O)NHCH 2 —CH 3 or N-Me-Aib-(D)-Trp-(D)-gTrp-C(O)NHCH 2 —CH 3 .