Patent ID: 8178651
Filing Date: 2012-05-15
Classification: A61K,A61P,C07D,C07K

Abstract:
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.