Compounds with growth hormone releasing properties
Compounds of peptide mimetic nature having the general formula I wherein a and b are independently 1 or 2, R 1 and R 2 are independently H or C 1-6 alkyl, G and J are independently, inter alia, aromats, and D and E are independently several different groups are growth hormone secretagogous with improved bioavailability.
1. A compound of Formula I
wherein
R 1 and R 2 are independently hydrogen, or C 1-6 -alkyl;
a and b are independently 1 or 2;
wherein R 27 , R 28 , R 32 , R 33 , R 34 , R 35 and R 36 independently are hydrogen;
wherein R 3 , R 4 , R 5 and R 6 are independently hydrogen or C 1-6 alkyl,
n, m, and q are independently 0, 1, 2, or 3;
when E is
—CONR 12 R 13
wherein R 12 is hydrogen and R 13 C 1-6 -alkyl,
or
wherein
X is —O—,
Z is —N═,
V is —C(R 16 )═
Y is —N═,
R 16 is —(CH 2 ) w R 19 ;
wherein R 19 is C 1-6 alkyl and w is independently, 0, 1, 2 or 3,
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein D is piperidin-4-ylidenyl or 2-methylpiperidin-4-yl.
3. The compound according to claim 1 , wherein E is methycarbamoyl or 3-methyl-1,2,4-oxadiazol-5-yl.
4. The compound according to claim 1 , wherein R 1 and R 2 independently are hydrogen, methyl or ethyl.
5. The compound according to claim 1 , wherein a and b independently are 1.
6. The compound according to claim 1 , wherein said compound is
7. A method of increasing rate and extent of growth, improving milk and/or wool production and/or treating ailments in an animal resulting from a deficiency of growth hormone, the method comprising administering to said animal in need thereof an effective amount of the compound according to claim 1 .
8. A composition comprising a compound according to claim 1 together with a pharmaceutically acceptable carrier or diluent.
9. The composition according to claim 8 in unit dosage form, comprising from about 10 to about 200 mg of said compound.
10. The composition according to claim 8 for oral, nasal, transdermal, pulmonary, or parenteral administration.
11. A method of stimulating the release of growth hormone from the pituitary, the method comprising administering to a subject in need thereof an effective amount of the compound according to claim 1 .
12. The method according to claim 11 , wherein the effective amount of said compound is in the range of from about 0.0001 to about 100 mg/kg body weight per day.
13. The method according to claim 11 , wherein said administration is carried out by the oral, nasal, transdermal, pulmonary, or parenteral route.
14. The method according to claim 11 , wherein the effective amount of said compound is in the range of from about 0.001 to about 50 mg/kg body weight per day.