Cyclic peptides multimers targeting alpha-4-beta-7 integrin
There is described herein, multimers comprising a plurality of compounds covalently linked together, the compounds independently being of formula (I).
1. A homodimer of two moieties covalently linked together by an amide bond to a diphenic acid residue, the moieties both being of formula (I):
wherein
R 1 is H;
R 2 is H;
R 3 is CH 3 ;
R 4 is H;
R 5 is an amide of the formula —C(O)NR**R***, wherein R** is H and R*** is tert-butyl;
R 6 along with R 7 together form the pyrrolidine ring of Pro;
R 8 is H;
n is 1;
wherein Z is an amino terminus of an amino acid; —C═O— adjacent L is the carboxy terminus of an amino acid; and L along with Z and —C═O— is a peptide having the following formula:
X y —X z —X 1 —X 2 —X 3
wherein
X y is 3-aminomethyl-4-[4-(1-piperazinyl)-phenyl]-benzoic acid, in which the piperazinyl amine nitrogen at the 4-position of the piperazinyl ring is covalently bound via the amide bond to the diphenic acid residue to form the homodimer;
X z is absent;
X 1 is Leucine;
X 2 is Asp; and
X 3 is Thr;
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising the homodimer of claim 1 along with a pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2 , formulated for oral delivery, topical delivery or parenteral delivery.