Nonapeptide and decapeptide analogs of LHRH, useful as LHRH agonist
First Claim
1. A compound of the formula
and the pharmaceutically acceptable salts thereof wherein;
A is tryptophyl, phenylalanyl, 3-(1-naphthyl)-L-alanyl or 3-(2-naphthyl)-L-alanine;
B is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl, ;
C is an amino acyl residue selected from the group consisting of the radicals represented by the following structural formulas;
(a) ##STR17## wherein n is 1 to 5;
R1 is alkyl of 1 to 12 carbon atoms, -NRR3 wherein R is hydrogen or alkyl of 1 to 4 carbon atoms, R3 is fluoroalkyl, alkyl of 1 to 12 carbon atoms, cycloalkyl, phenyl, benzyl, --(CH2)n -morpholino or --(CH2)n N(R4)2 wherein n is 1 to 5 and R4 is lower alkyl;
R2 is hydrogen or R3 ;
or R1 and R2 comprise a ring represented by the following structural formulas;
##STR18## wherein n is 1 to 7;
A is hydrogen, alkyl of 1 to 6 carbon atoms or cycloalkyl; and
X is halo or A or(b) ##STR19## wherein R5 is alkyl of 1 to 6 carbon atoms, benzyl, phenylethyl, cyclohexyl, cyclopentyl; and
R6, R7 and R8 are hydrogen or alkyl of 1 to 4 carbon atoms; and
n is the integer 2-5;
or(c) a substituent of the formula ##STR20## wherein R9 is hydrogen, alkyl of 1 to 12 carbon atoms, phenyl or phenylloweralkyl;
E is arginyl or leucyl; and
D is leucyl, isoleucyl, nor-leucyl or N-methylleucyl;
F is glycinamide or -NH-R1, wherein R1 is lower alkyl, cycloalkyl, fluoro lower alkyl or --NH--CO--NH--R2 wherein R2 is hydrogen or lower alkyl.
1 Assignment
0 Petitions
Accused Products
Abstract
Synthetic nonapeptide and decapeptide LHRH agonists analogs having a novel gaunadino-substituted, amidine, tertiary or quatrinary aminoacyl residue at position 6 are disclosed herein.
-
Citations
23 Claims
- 1. A compound of the formula
- space="preserve" listing-type="equation">(pyro)Glu-His-A-Ser-B-C-D-Ed-Pro-F (I)
and the pharmaceutically acceptable salts thereof wherein; A is tryptophyl, phenylalanyl, 3-(1-naphthyl)-L-alanyl or 3-(2-naphthyl)-L-alanine; B is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl, ; C is an amino acyl residue selected from the group consisting of the radicals represented by the following structural formulas; (a) ##STR17## wherein n is 1 to 5; R1 is alkyl of 1 to 12 carbon atoms, -NRR3 wherein R is hydrogen or alkyl of 1 to 4 carbon atoms, R3 is fluoroalkyl, alkyl of 1 to 12 carbon atoms, cycloalkyl, phenyl, benzyl, --(CH2)n -morpholino or --(CH2)n N(R4)2 wherein n is 1 to 5 and R4 is lower alkyl; R2 is hydrogen or R3 ;
or R1 and R2 comprise a ring represented by the following structural formulas;
##STR18## wherein n is 1 to 7;
A is hydrogen, alkyl of 1 to 6 carbon atoms or cycloalkyl; and
X is halo or A or(b) ##STR19## wherein R5 is alkyl of 1 to 6 carbon atoms, benzyl, phenylethyl, cyclohexyl, cyclopentyl; and
R6, R7 and R8 are hydrogen or alkyl of 1 to 4 carbon atoms; and
n is the integer 2-5;
or(c) a substituent of the formula ##STR20## wherein R9 is hydrogen, alkyl of 1 to 12 carbon atoms, phenyl or phenylloweralkyl; E is arginyl or leucyl; and D is leucyl, isoleucyl, nor-leucyl or N-methylleucyl; F is glycinamide or -NH-R1, wherein R1 is lower alkyl, cycloalkyl, fluoro lower alkyl or --NH--CO--NH--R2 wherein R2 is hydrogen or lower alkyl. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23)
Specification