Somatostatin-dopamine chimeric analogs

1. A compound of the 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;

each of R2 and R3 is, 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—, —S—, —S(O)—, or —S(O) 2 —;

m is 1;

n is 0-10;

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

p is 1-10; and

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

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 of the formula

wherein:

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

R 5 is H, C 1-6 alkyl, or arylalkyl; and

n is an integer between 0 and 10 inclusive;

or a pharmaceutically acceptable salt thereof.

3. A compound according to one of claim 1 or 2 , wherein said compound is:

(6-N-propyl-8β-ergolinyl)methylthioacetic acid;

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

(6-N-methyl-8β-ergolinyl)methylthioacetic acid; or

Ethyl(6-N-methyl-8β-ergolinyl)methylthioacetate;

or a pharmaceutically acceptable salt thereof.

4. A process for the synthesis of a compound according to claim 2 wherein R 5 is C 1-6 alkyl or arylalkyl, comprising the step of:

treating a compound of the formula

with methanesulfonyl chloride in pyridine, and subsequently with a compound of formula HS(CH 2 ) n —CO 2 —R 5 , wherein R 5 is C 1-6 alkyl or arylalkyl,

in order to yield a compound according to claim 2 in which R 5 is C 1-6 alkyl or arylalkyl.

5. A process for the synthesis of a compound according to claim 2 wherein R 5 is H, comprising the step of:

hydrolyzing the compound of the formula

wherein R 5 is C 1-6 alkyl or arylalkyl as obtained in claim 4 ,

in order to yield a compound according to claim 2 in which R 5 is H.

6. A process for the synthesis of a compound of the formula

wherein:

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

n is an integer between 0 and 10 inclusive,

comprising the steps of:

(a) coupling a compound of the formula

with partially protected somatostatin; and

(b) deprotecting the resulting compound.

7. A process for the synthesis of a compound of the formula

wherein:

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

n is an integer between 0 and 10 inclusive,

comprising the steps of:

(a) coupling a compound of the formula

with an optionally partially protected somatostatin derivative; and

(b) when the somatostatin derivative is partially protected, deprotecting the resulting compound.