Unlock instant, AI-driven research and patent intelligence for your innovation.

4-amino-4-oxobutanoyl peptides as inhibitors of viral replication

An alkyl and phenyl technology, applied in the field of 4-amino-4-oxobutyryl peptides as virus replication inhibitors, can solve problems such as lack of high mutation rate of HCV

Inactive Publication Date: 2013-05-22
ACHILLION PHARMA INC
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the lack of effective therapies for certain HCV strains and due to the high mutation rate of HCV, new therapies are needed

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 4-amino-4-oxobutanoyl peptides as inhibitors of viral replication
  • 4-amino-4-oxobutanoyl peptides as inhibitors of viral replication
  • 4-amino-4-oxobutanoyl peptides as inhibitors of viral replication

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0318] Example 1. 1-((2S,4R)-1-((S)-2-tert-butyl-4-oxo-4-(piperidin-1-yl)butyryl)-4-(7-methoxy Of 2-phenylquinolin-4-yloxy)pyrrolidine-2-carboxamido)-2-vinylcyclopropane carboxylic acid

[0319] Step 1. Preparation of N-(cyclopropylsulfonyl)-1-(BOC-amino)-2-vinylcyclopropane carboxamide

[0320]

[0321] CDI (2.98 g, 18.4 mm, 1.1 eq) was dissolved in ethyl acetate. N-Boc-cyclopropyl vinyl acid (3.8g, 16.7mm, 1.0eq) (prepared by the method given by Beaulieu, PL, etc. (J.Org.Chem.70:5869-79 (2005)) was added to CDI / Ethyl acetate mixture, stirred at room temperature until the starting material was consumed. Cyclopropylsulfonamide (2.2g, 18.4mm, 1.1eq) was added to this mixture, and then DBU (2.1ml, 20.5mm, 1.23eq) ), the mixture was stirred at room temperature for 2 hours. Treatment and purification by silica gel chromatography provided 2 g of compound 2.

[0322] Step 2. Preparation of (2S, 4R)-tert-butyl 2-(1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-(7-methox...

Embodiment 2

[0339] Example 2. Synthesis of macrocyclic compounds

[0340] General operation

[0341] Procedure 1. Deprotection reaction (convert N-Boc to amine or t-butyl ester to carboxylic acid)

[0342] TFA (3-4ml) was added to a solution of Boc-protected starting material (1 mmol) or tert-butyl ester in dry DCM (7ml) at room temperature. The reaction should be monitored by LC / MS and TLC. After 1 to 3 hours, the reaction mixture was evaporated to dryness under reduced pressure. The crude product was used for the next reaction without further purification.

[0343] Procedure 2. Amide formation

[0344] At room temperature, N-methylmorpholine (2 mmol) and HBTU (1.2 mmol) were added to a solution of acid (1 mmol) in dry DMF (10 ml) at once. After stirring for 10 minutes at room temperature, amine (1 mmol) was added in one portion, and then stirred overnight. The reaction mixture was poured into ice water, and extraction was performed with ethyl acetate (100 ml). Use H 2 O. Wash the organic la...

Embodiment 3

[0372] Example 3. Other tertiary amine substituted peptides

[0373]

[0374]

[0375]

[0376]

[0377]

[0378]

[0379]

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides 4-amino-4-oxobutanoyl peptide compounds of Formula I (I) and the pharmaceutically salts and hydrates thereof. The variables R1-R9, R16, R18 R19, n, M,, n, M,, and Z are defined herein. Certain compounds of Formula I are useful as antiviral agents. Certain 4-amino-4-oxobutanoyl peptide compounds disclosed herein are potent and / or selective inhibitors of viral replication, particularly Hepatitis C virus replication. The invention also provides pharmaceutical compositions containing one or more 4-amino-4-oxobutanoyl peptide compounds and one or more pharmaceutically acceptable carriers. Such pharmaceutical compositions may contain 4-amino-4-oxobutanoyl peptide compound as the only active agent or may contain a combination of 4-amino-4-oxobutanoyl peptide containing peptides compound and one or more other pharmaceutically active agents. The invention also provides methods for treating viral infections, including Hepatitis C infections, in mammals.

Description

[0001] Cross references to related applications [0002] This application claims priority for US provisional patent application 60 / 830,488 filed on July 13, 2006 and 60 / 945,786 filed on June 2, 2007, both of which are incorporated herein by reference in their entirety. Technical field [0003] The present invention provides 4-amino-4-oxobutyryl peptides useful as antiviral agents. Certain 4-amino-4-oxobutyryl peptides disclosed herein are strong and / or selective inhibitors of viral replication (particularly hepatitis C virus replication). The invention also provides a pharmaceutical composition containing one or more 4-amino-4-oxobutyryl peptides and one or more pharmaceutically acceptable carriers, excipients or diluents. These pharmaceutical compositions may contain 4-amino-4-oxobutyryl peptide as the sole active agent or may contain 4-amino-4-oxobutyryl peptide or a combination of related compounds and one or more other pharmaceutically active agents . The invention also prov...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/02C07K5/06C07K5/08A61K38/00
Inventor 阿维纳什·帕德克王祥柱张所明阿图尔·阿加瓦尔
Owner ACHILLION PHARMA INC