Somatostatin-dopamine chimeric analogs

1. A method of treating acromegaly, GH secreting adenomas, or prolactin secreting adenomas in a subject, said method comprising administering to said subject a therapeutically effective amount of:

a) a compound of Formula (I),

wherein:

X is H, Cl, Br, I, F, —CN, or C 1-5 alkyl;

R1 is H, C 1-4 alkyl, allyl, alkenyl or —CN;

R2 and R3, each are, independently H or absent, provided that when R2 and R3 are absent a double bond is present between the carbon atoms to which they are attached;

R4 is H or —CH 3 ;

Y is —O—, —C(O)—, —S—, —S—(CH 2 )s-C(O)—, —S(O)—, —S(O) 2 —, —SC(O)—, —OC(O)—, —N(R5)-C(O)—, or —N(R6)-;

R5, R6, R7 and R8 each is, independently, H or C 1-5 alkyl;

R6 is H or C 1-5 alkyl;

m is 0 or 1;

n is 0-10;

L is —(CH 2 )p-C(O)—, when Y is —S—, —S(O)—, —S(O) 2 —, —O— or —N(R6)-;

L is —C(O)—(CR7R8)q-C(O)—, when Y is —N(R6)-, —O—, or —S—;

L is -(Doc)t-, when Y is —C(O)—, SC(O)—, —OC(O)—, —S—(CH 2 )s-C(O)—, or —N(R5)-C(O)—;

p is 1-10;

q is 2-4;

s is 1-10;

t is 1-10; and

z is a somatostatin analog or a moiety comprising —H, —OH, (C 1 -C 6 )alkoxy, arylalkoxy, —NH 2 , or —NR9R10, wherein R9 and R10 each is, independently, H or C 1-5 alkyl;

or a pharmaceutically acceptable salt thereof; or

b) a compound of Formula (II),

wherein:

X is H, Cl, Br, I, F, —CN, or C 1-5 alkyl;

R1 is C1-4 alkyl, H, allyl, alkenyl or —CN;

R2 and R3, each are, independently H or absent, provided that when R2 and R3 are absent a double bond is present between the carbon atoms to which they are attached;

R4 is H or —CH 3 ;

R5 is C1-5 alkyl group, or a group of the formula of —(CH 2 )rN(CH 3 )q;

Y is —O—, —C(O)—, —S—, —SC(O)—, —OC(O)—, —N(R6)-C(O)—, —N(R7)-, or —N(R8)-(CH 2 )s-C(O)—;

R6, R7, R8, R9 and R10 each is, independently, H or C 1-5 alkyl;

L is —(CH 2 )p-C(O)—, when Y is —S—, —O— or —N(R7)-;

L is —C(O)—(CR9R10)q—C(O)—, when Y is —N(R7)-, —O—, or —S—;

L is -(Doc)t-, when Y is —C(O)—, SC(O)—, —OC(O)—, —N(R8)-(CH 2 )s-C(O)—, or —N(R6)-C(O)—;

m is 0 or 1;

n is 2-10;

r is 1-8;

q is 2-4;

p is 1-10;

s is 1-10;

t is 1-10; and

z is a somatostatin analog or a moiety comprising —H, —OH, (C 1 -C 6 )alkoxy, arylalkoxy, —NH 2 , or —NR9R10;

or a pharmaceutically acceptable salt thereof; or

c) a compound of formulae:

or a pharmaceutically acceptable salt thereof; or

d) a compound according to formulae:

or a pharmaceutically acceptable salt thereof; or

e) a compound according to formulae:

Ethyl-[6-methyl-8β-ergolinylmethyl]thioacetate;

6-Methyl-8β-ergolinylmethylthioacetyl-D-Phe-c(Cys-Tyr-D-Trp-Lys-Abu-Cys)-Thr-NH 2 ;

Ethyl-(6-n-propyl-8β-ergolinyl)methylthioacetate;

6-n-propyl-8β-ergolinylmethylthioacetyl-D-Phe-c(Cys-Tyr-D-Trp-Lys-Abu-Cys)-Thr-NH 2 ;

6-D-Methyl-8β-ergolinylmethylthlaminosuccinoyl-D-Phe-c(Cys-Tyr-D-Trp-Lys-Abu-Cys)-Thr-NH 2 ;

or a pharmaceutically acceptable salt thereof; or

f) a compound according to formulae:

or a pharmaceutically acceptable salt thereof,

wherein said therapeutically effective amount of said compound or pharmaceutically acceptable salt thereof treats acromegaly, GH secreting adenomas, or prolactin secreting adenomas in said subject in need thereof.

2. A method according to claim 1 , wherein said disease is acromegaly.

3. A method according to claim 1 , wherein said disease is a GH secreting adenoma.

4. A method according to claim 1 , wherein said disease is a prolactin secreting adenoma.

5. A method of treating, acromegaly, GH secreting adenomas, or prolactin secreting adenomas in a subject, said method comprising administering to said subject a therapeutically effective amount of

or a pharmaceutically acceptable salt thereof;

wherein said therapeutically effective amount of said compound or pharmaceutically acceptable salt thereof treats, acromegaly, GH secreting adenomas, or prolactin secreting adenomas in said subject in need thereof.

6. A method according to claim 5 , wherein said disease is selected from the group consisting of acromegaly, GH secreting adenomas and prolactin secreting adenomas.

7. A method according to claim 6 , wherein said disease is acromegaly.

8. A method according to claim 6 , wherein said disease is a GH secreting adenoma.

9. A method according to claim 6 , wherein said disease is a prolactin secreting adenoma.

10. A method of treating acromegaly, GH secreting adenomas, or prolactin secreting adenomas in a subject, said method comprising administering to said subject a therapeutically effective amount of

or a pharmaceutically acceptable salt thereof;

wherein said therapeutically effective amount of said compound or pharmaceutically acceptable salt thereof treats acromegaly, GH secreting adenomas, or prolactin secreting adenomas in said subject in need thereof.

11. A method according to claim 10 , wherein said disease is selected from the group consisting of acromegaly, GH secreting adenomas and prolactin secreting adenomas.

12. A method according to claim 11 , wherein said disease is acromegaly.

13. A method according to claim 11 , wherein said disease is a GH secreting adenoma.

14. A method according to claim 11 , wherein said disease is a prolactin secreting adenoma.