US 11,814,444 B2
Cyclic polypeptides for PCSK9 inhibition
Alonso Ricardo, Cambridge, MA (US); Nicolas Cedric Boyer, Somerville, MA (US); Joseph R. Stringer, Somerville, MA (US); Derek M. LaPlaca, Somerville, MA (US); Ketki Ashok Dhamnaskar, Cambridge, MA (US); Zhong Ma, Lexington, MA (US); Jonathan C. Blain, Melrose, MA (US); and Rohit Vyasamneni, Billerica, MA (US)
Assigned to Ra Pharmaceuticals, Inc., Cambridge, MA (US)
Appl. No. 17/253,764
Filed by Ra Pharmaceuticals, Inc., Cambridge, MA (US)
PCT Filed Jun. 20, 2019, PCT No. PCT/US2019/038220
§ 371(c)(1), (2) Date Dec. 18, 2020,
PCT Pub. No. WO2019/246386, PCT Pub. Date Dec. 26, 2019.
Claims priority of provisional application 62/688,034, filed on Jun. 21, 2018.
Prior Publication US 2022/0348610 A1, Nov. 3, 2022
Int. Cl. A61K 38/00 (2006.01); C07K 7/02 (2006.01)
CPC C07K 7/02 (2013.01) [A61K 38/00 (2013.01)] 25 Claims
 
1. A cyclic peptide having the structure of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof;
wherein:
A1 is an acyl or sulfonyl protected amino acid selected from the group consisting of

OG Complex Work Unit Chemistry
or is an acyl protected amine;
R4 is selected from the group consisting of the amino acid side chains of ALA, THR,

OG Complex Work Unit Chemistry
R5 is selected from the group consisting of the amino acid side chains of

OG Complex Work Unit Chemistry
R6 is selected from the group consisting of the amino acid side chains of

OG Complex Work Unit Chemistry
R7 is selected from the group consisting of the amino acid side chains of GLU,

OG Complex Work Unit Chemistry
R8 is selected from the group consisting of the amino acid side chains of HIS, GLU, TYR,

OG Complex Work Unit Chemistry
ALA;
R9 is selected from the group consisting of the amino acid side chains of

OG Complex Work Unit Chemistry
ALA, and GLU;
R10 is selected from the group consisting of the amino acid side chains of

OG Complex Work Unit Chemistry
P1 is H, methyl, an acetyl group, or

OG Complex Work Unit Chemistry
n is 0 or 1;
p is 2, 3, or 4;
wherein each amino acid residue is optionally an N-methylated amino acid; and
wherein each amino acid residue can be in the R or S configuration.