Organic compounds
First Claim
Patent Images
1. A compound of formula I, ##STR53## wherein R1 is (i) H,(ii) NH2,(iii) H--Ala--NH--;
- H--Tyr--NH--;
H--Cys--NH--;
H--Val--NH--;
H--Lys--NH--;
H--(α
-amino-isobutyryl)--NH--;
H--Phe--NH(iv) NH2 --NH--CO--NH--;
(v) C6 H5.NH--CO--Gly--NH--;
H--Ala--Gly--NH--;
H--Val--Gly--NH--;
H--α
--phenyl--Gly--NH--,(vi) R2 --A--CO--NH--, whereinR2 is lower alkyl, phenyl, or phenyl substituted by halogen, hydroxy, amino lower alkyl or lower alkoxy,A is a direct bond, alkylene containing up to 6 carbon atoms or --NH--,(vii) R2 --Ala--NH--;
R2 --Ala--Gly--NH--;
wherein R2 is as defined above,(viii) C6 H5.AI.CO--M--NH--, whereinAI is an alkylene chain of up to 6 carbon atoms, and--M-- is --(mono- or di-Hal)--Phe, --Gly-- or --Ala--,(ix) T--(mono- or di-Hal)--Phe--NH, wherein T-- is H--, H--Val-- or benzoyl--,(x) ##STR54## wherein AI is as defined above, and--L-- is --Val--(mono- or di-Hal)-- Phe--α
--phenyl--Gly--, andn is an integer between 4 and 10,each B is hydrogen or the two radicals B form a direct bond,X is --Lys--, or --Nle--, andY is --Asn--, --Gln-- or --Thr--, andZ signifies the radicals;
(i) --CO--asparaginol;
--CO--leucinol;
--CO--iso-leucinol;
--CO--valinol;
--CO--norleucinol;
--CO--glutaminol;
--CO--threoninol;
(ii) --CO--Leu;
--CO--Ser;
--CO--Iso--Leu;
--CO--Val, and their corresponding amides, wherein the amide portion signifies the radical --CO--NR4 R5 (wherein R4 and R5 independently are hydrogen or lower alkyl) or the radical ##STR55## (wherein n is as defined above);
(iii) --CO--ThrOR3 or --CO--SerOR3 (wherein R3 is lower alkyl);
or(iv) --CO--NH--(CH2)k --OH (wherein k is an integer between 2 and
6), or ##STR56## (wherein 11 and 12 independently signify a whole number from 1 to
6);
wherein in formula I the unit containing radicals R1, X, Y and Z, as well as in the remaining units of the peptide sequence, at least one unit may be present in D form,with the proviso that when R1 is H--Cys--NH or H--(D)--Cys--NH, B--B is other than a direct bond,or a pharmaceutically acceptable acid addition salt or complex thereof.
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Abstract
This invention provides new compounds of formula I, ##STR1## wherein R1, X, Y and Z are amino acid residues and
each B is hyrogen or together are a bond,
useful as growth hormone secretion inhibitors.
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Citations
7 Claims
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1. A compound of formula I, ##STR53## wherein R1 is (i) H,
(ii) NH2, (iii) H--Ala--NH--; - H--Tyr--NH--;
H--Cys--NH--;
H--Val--NH--;
H--Lys--NH--;
H--(α
-amino-isobutyryl)--NH--;
H--Phe--NH(iv) NH2 --NH--CO--NH--; (v) C6 H5.NH--CO--Gly--NH--;
H--Ala--Gly--NH--;
H--Val--Gly--NH--;
H--α
--phenyl--Gly--NH--,(vi) R2 --A--CO--NH--, wherein R2 is lower alkyl, phenyl, or phenyl substituted by halogen, hydroxy, amino lower alkyl or lower alkoxy, A is a direct bond, alkylene containing up to 6 carbon atoms or --NH--, (vii) R2 --Ala--NH--;
R2 --Ala--Gly--NH--;
wherein R2 is as defined above,(viii) C6 H5.AI.CO--M--NH--, wherein AI is an alkylene chain of up to 6 carbon atoms, and --M-- is --(mono- or di-Hal)--Phe, --Gly-- or --Ala--, (ix) T--(mono- or di-Hal)--Phe--NH, wherein T-- is H--, H--Val-- or benzoyl--, (x) ##STR54## wherein AI is as defined above, and --L-- is --Val--(mono- or di-Hal)-- Phe--α
--phenyl--Gly--, andn is an integer between 4 and 10, each B is hydrogen or the two radicals B form a direct bond, X is --Lys--, or --Nle--, and Y is --Asn--, --Gln-- or --Thr--, and Z signifies the radicals; (i) --CO--asparaginol;
--CO--leucinol;
--CO--iso-leucinol;
--CO--valinol;
--CO--norleucinol;
--CO--glutaminol;
--CO--threoninol;(ii) --CO--Leu;
--CO--Ser;
--CO--Iso--Leu;
--CO--Val, and their corresponding amides, wherein the amide portion signifies the radical --CO--NR4 R5 (wherein R4 and R5 independently are hydrogen or lower alkyl) or the radical ##STR55## (wherein n is as defined above);
(iii) --CO--ThrOR3 or --CO--SerOR3 (wherein R3 is lower alkyl);
or(iv) --CO--NH--(CH2)k --OH (wherein k is an integer between 2 and
6), or ##STR56## (wherein 11 and 12 independently signify a whole number from 1 to
6);
wherein in formula I the unit containing radicals R1, X, Y and Z, as well as in the remaining units of the peptide sequence, at least one unit may be present in D form,with the proviso that when R1 is H--Cys--NH or H--(D)--Cys--NH, B--B is other than a direct bond, or a pharmaceutically acceptable acid addition salt or complex thereof. - View Dependent Claims (2, 3, 4, 6, 7)
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6. A pharmaceutical composition useful in inhibiting growth hormone secretion comprising as active ingredient a pharmaceutically effective amount of a compound of formula I as defined in claim 1.
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7. A method of inhibiting growth hormone secretion in a subject in need of such treatment, which method comprises administering an effective amount of a compound of formula I as defined in claim 1.
- H--Tyr--NH--;
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5. A compound of formula ##STR62##
Specification