Supercharge Your Innovation With Domain-Expert AI Agents!

4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxamide compounds

A compound, formamide technology, applied in the field of thrombin inhibitors, can solve problems such as inactivity

Inactive Publication Date: 2005-10-12
SERVIER LAB
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, there are direct inhibitors of thrombin, however, these peptide substances have the disadvantage that they are inactive when administered orally

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-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxamide compounds
  • 4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxamide compounds
  • 4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxamide compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0110] Example 1: 3-{[2,2-difluoro-2-(1-oxo-2-pyridyl)ethyl]amino}-N-(2-fluoro-benzyl)-4-oxo-4 , 6,7,8-Tetrahydropyrrolo[1,2-a]pyrazine-6-carboxamide

[0111] Step A: N-tert-butoxycarbonyl-5-oxoproline benzyl ester

[0112] At 0° C., 11 mmol of dimethylaminopyridine and 11 mmol of di-tert-butyl dicarbonate were added to 10 mmol of 5-oxoproline benzyl ester (its preparation method is described in the following literature: E.Campaigne et al. ( J.Heterocyd.Chem.1975,12,391)) in dichloromethane solution. After stirring at room temperature for 24 hours, the reaction mixture was washed, then dried and evaporated to give the desired product as a viscous oil.

[0113] Step B: N-tert-butoxycarbonyl-5-hydroxyproline benzyl ester

[0114]Under an argon atmosphere at -78°C, 18 mmol of a 1M hexane solution of diisobutylaluminum hydride was added to 10 mmol of the compound obtained in the above step in tetrahydrofuran. After stirring at -78°C for 20 minutes, saturated aqueous ammonium c...

Embodiment 2

[0140] Example 2: (6R)-3-{[2,2-difluoro-2-(1-oxo-2-pyridyl)ethyl]amino}-N-(2-fluoro-benzyl)-4- Oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrazine-6-carboxamide

[0141] The racemic mixture of Example 1 was separated by chiral phase preparative HPLC chromatography (Chiralpak AD column, eluent: acetonitrile / isopropanol / diethylamine 500 / 500 / 1).

[0142] The desired product is the first enantiomer obtained.

Embodiment 3

[0143] Example 3: (6S)-3-{[2,2-difluoro-2-(1-oxo-2-pyridyl)ethyl]amino}-N-(2-fluoro-benzyl)-4- Oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrazine-6-carboxamide

[0144] The racemic mixture of Example 1 was separated by chiral phase preparative HPLC chromatography (Chiralpak AD column, eluent: acetonitrile / isopropanol / diethylamine 500 / 500 / 1).

[0145] The desired product is the second enantiomer obtained.

[0146] Optical rotation index: α D =-116.07° (methanol, 20°C, c=1.4)

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

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Login to View More

Abstract

Compound of formula (I): wherein: (a) represents 1-oxidopyridyl substituted by the remainder of the molecule in any one of the positions 2, 3 and 4, m and n, which may be identical or different, each represent an integer of from 1 to 3, R1 represents hydrogen or alkyl, R2 and R3, which may be identical or different, each represent an atom or group selected from hydrogen, halogen, alkyl, hydroxy, acyloxy and alkoxy, or, together with the carbon atom carrying them, form a cycloalkane having from 3 to 6 carbon atoms, R4 and R5 each represent hydrogen, or are adjacent and, together with the carbon atoms carrying them, form a benzo ring, Ar represents aryl or heteroaryl. Medicinal products containing the same are also provided.

Description

technical field [0001] The present invention relates to novel 4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxamide compounds, processes for their preparation and pharmaceutical compositions containing them, and their use as thrombin inhibitors. Background technique [0002] Thrombin, the key enzyme of blood coagulation, plays an important role in the pathology of venous and arterial thrombosis, and it can significantly cause the automagnification of the coagulation cascade (F.Toti et al., Sang, Thrombose, Vaisseaux 1992, 4, 483-494 and T.M. Reilly et al., Blood Coagulation and Fibrinolysis 1992, 3, 513-517). [0003] Direct and specific inhibition of thrombin appeared to be more effective and associated with a lower risk of bleeding than treatment with heparin. Currently, there are direct inhibitors of thrombin, however, these peptide substances have the disadvantage that they are inactive when administered orally. [0004] Peptidomimetic compounds with oral anti...

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
IPC IPC(8): A61K31/519A61P7/02A61P9/00A61P9/10A61P43/00C07D487/04
CPCC07D487/04A61P43/00A61P7/00A61P7/02A61P9/00A61P9/02A61P9/10A61P9/14A47J27/16A47J36/24A47J27/13
Inventor G·德南特伊P·格洛阿内克J-G·帕尔芒捷A·贝诺斯特A·吕潘M-O·瓦莱T·韦伯朗
Owner SERVIER LAB
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com