GLP-1 receptor agonists and uses thereof

Patent metadata

Field	Value
Publication number	US-12319669-B2
Application number	US-202318477050-A
Country	US
Kind code	B2
Filing date	Sep 28, 2023
Priority date	Dec 16, 2016
Publication date	Jun 3, 2025
Grant date	Jun 3, 2025

Abstract

Provided herein are 6-carboxylic acids of benzimidazoles and 4-aza-, 5-aza-, 7-aza- and 4,7-diaza-benzimidazoles as GLP-1R agonists, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.

First claim

What is claimed is:

1. A method for treating a disease or disorder in a human comprising administering to the human a compound that is 2-[(4-{6-[(4-cyano-2-fluorophenyl)methoxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-{[(2S)-oxetan-2-yl]methyl}-1H-benzimidazole-6-carboxylic acid or 2-[(4-{6-[(4-cyano-2-fluorophenyl)methoxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-{[(2R)-oxetan-2-yl]methyl}-1H-benzimidazole-6-carboxylic acid, or a pharmaceutically acceptable salt thereof, wherein the disease or disorder is selected from the group consisting of Type 1 diabetes (T1D), Type 2 diabetes mellitus (T2DM), pre-diabetes, idiopathic T1D, latent autoimmune diabetes in adults (LADA), early-onset T2DM (EOD), youth-onset atypical diabetes (YOAD), maturity onset diabetes of the young (MODY), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, a kidney disease, and diabetic retinopathy.

2. The method of claim 1 wherein the disease or disorder is T1D or idiopathic T1D.

3. The method of claim 1 wherein the disease or disorder is selected from the group consisting of T2DM, pre-diabetes, LADA, EOD, YOAD, MODY, malnutrition-related diabetes, gestational diabetes, diabetic neuropathy, diabetic nephropathy, and diabetic retinopathy.

4. The method of claim 1 wherein the disease or disorder is T2DM.

5. The method of claim 1 wherein the disease or disorder is selected from the group consisting of hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, and a kidney disease.

6. A method for treating a disease or disorder in a human comprising administering to the human a compound that is 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid, or a pharmaceutically acceptable salt thereof, wherein disease or disorder is selected from the group consisting of T1D, T2DM, pre-diabetes, idiopathic T1D, LADA, EOD, YOAD, MODY, malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease, and diabetic retinopathy.

7. The method of claim 6 wherein the compound is 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid.

8. The method of claim 6 wherein the compound is a pharmaceutically acceptable salt of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid.

9. The method of claim 6 wherein the compound is 2-amino-2-(hydroxymethyl)propane-1,3-diol salt (tris salt) of 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-[(2S)-oxetan-2-ylmethyl]-1H-benzimidazole-6-carboxylic acid.

10. The method of claim 6 wherein the disease or disorder is T1D or idiopathic T1D.

11. The method of claim 6 wherein the disease or disorder is selected from the group consisting of T2DM, pre-diabetes, LADA, EOD, YOAD, MODY, malnutrition-related diabetes, gestational diabetes, diabetic neuropathy, diabetic nephropathy, and diabetic retinopathy.

12. The method of claim 6 wherein the disease or disorder is T2DM.

13. The method of claim 6 wherein the disease or disorder is selected from the group consisting of hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, and a kidney disease.

14. The method of claim 8 wherein the disease or disorder is T1D or idiopathic T1D.

15. The method of claim 8 wherein the disease or disorder is selected from the group consisting of T2DM, pre-diabetes, LADA, EOD, YOAD, MODY, malnutrition-related diabetes, gestational diabetes, diabetic neuropathy, diabetic nephropathy, and diabetic retinopathy.

16. The method of claim 8 wherein the disease or disorder is T2DM.

17. The method of claim 8 wherein the disease or disorder is selected from the group consisting of hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, and a kidney disease.

18. The method of claim 9 wherein the disease or disorder is T1D or idiopathic T1D.

19. The method of claim 9 wherein the disease or disorder is selected from the group consisting of T2DM, pre-diabetes, LADA, EOD, YOAD, MODY, malnutrition-related diabetes, gestational diabetes, diabetic neuropathy, diabetic nephropathy, and diabetic retinopathy.

20. The method of claim 9 wherein the disease or disorder is T2DM.

21. The method of claim 9 wherein the disease or disorder is selected from the group consisting of hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, and a kidney disease.

Assignees

• Pfizer

Inventors

• Aspnes Gary Erik
• Bagley Scott W
• Curto John M
• Dowling Matthew S
• Edmonds David
• Flanagan Mark E
• Futatsugi Kentaro
• Griffith David A
• Huard Kim
• Ingle Gajendra
• Jiao Wenhua
• Limberakis Chris
• Mathiowetz Alan M
• Piotrowski David W
• Ruggeri Roger B

Classifications

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title