Novel GLP-1 Analogues

Patent metadata

Field	Value
Publication number	US-2020362007-A1
Application number	US-202016985207-A
Country	US
Kind code	A1
Filing date	Aug 4, 2020
Priority date	Apr 5, 2018
Publication date	Nov 19, 2020
Grant date	—

Abstract

The present disclosure pertains to novel Glucagon like Peptide-1 (GLP-1) (7-37) analogs having an amino acid sequence with Leu or Ile at the C-terminal. The new analogs are potent GLP-1 agonists with reduced adverse effect and improved duration of action. The present disclosure further relates to acylated derivatives of the new analogs which have further improved potency and duration of action and are suitable for oral administration. The analogs of present disclosure may be useful in treatment of diabetes and obesity.

First claim

We claim:

1 . A polypeptide comprising the amino acid sequence:

wherein DSer is a serine residue having a D-configuration and DLeu is a leucine residue having a D-configuration;
wherein Ser(OMe) is a serine residue having the structure:

wherein Moiety A has the structure:

wherein Moiety B has the structure:

wherein Moiety C has the structure:

wherein Moiety D has the structure:

wherein Moiety E has the structure:

and
wherein Moiety F has the structure:

2 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety A has the structure:

3 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Ser(OMe) is a serine residue having the structure:

and
wherein Moiety A has the structure:

4 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety A has the structure:

5 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein DLeu is a leucine residue having a D-configuration; and
wherein Moiety A has the structure:

6 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety A has the structure:

7 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety B has the structure:

8 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety B has the structure:

9 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety A has the structure:

10 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein DSer is a serine residue having a D-configuration and DLeu is a leucine residue having a D-configuration;
wherein Ser(OMe) is a serine residue having the structure:

and
wherein Moiety A has the structure:

11 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein DSer is a serine residue having a D-configuration; and
wherein Moiety A has the structure:

12 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein DLeu is a leucine residue having a D-configuration; and
wherein Moiety A has the structure:

13 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety A has the structure:

14 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety C has the structure:

15 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety C has the structure:

16 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety C has the structure:

17 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence:

wherein Moiety D has the structure:

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Thennati Rajamannar
• Chaturvedi Nishith
• Burade Vinod Sampatrao
• Shahi Pradeep Dinesh
• Natarajan Muthukumaran
• Nagaraja Ravishankara Madavati
• Zalawadia Rishit Mansukhlal
• Patel Vipulkumar Shankarbhai
• Pandya Kunal
• Patel Brijeshkumar
• Joshi Dhiren Rameshchandra
• Soni Krunal Harishbhai
• Tiwari Abhishek

Classifications

• A61K38/26

  Glucagons · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07K14/605 Primary

  Glucagons · CPC title