Indole derivatives

A technology of indole derivatives and indole, which is applied in the field of indole derivatives and can solve problems such as undisclosed compounds

Inactive Publication Date: 2013-07-10
RICHTER GEDEON NYRT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, none of these prior art references disclose any compounds within the scope of compounds of the class described herein below

Method used

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[0146] The foregoing ingredients and various preparation routes are representative only. Other materials and process techniques known in the art can also be used.

[0147] The compounds of the present invention are bradykinin receptor antagonists, in particular selective bradykinin B1 receptor antagonists, and are therefore useful in the treatment or prevention of conditions including pain and inflammation, which include feeding into the breast to be treated An effective amount of the compound of formula (I) of the present invention is administered to the animal as it is or in the form of a medicament.

[0148] The compounds will be effective in the treatment of musculoskeletal pain and disorders of the body, including bone and joint pain and disorders (e.g., arthritis, including rheumatoid and other types of inflammatory arthritis, osteoarthritis , spondylitis and infectious arthritis, arthritis caused by gout or pseudogout, autoimmune and vasculitic joint disorders such as ...

Embodiment 1

[0469] 1-(2,2,2-Trifluoro-acetylamino)-cyclopropanecarboxylic acid 4-[3-chloro-2-(2-methyl-2H- Tetrazol-5-yl)-indol-1-yl]-benzylamide

[0470] To 4.0g (8.7mmol) 1-amino-cyclopropanecarboxylic acid 4-[3-chloro-2-(2-methyl-2H-tetrazol-5-yl)-indol-1-yl]-benzyl In a stirred solution of amide hydrochloride (reference example 4) and 3.6mL (25.8mmol) triethylamine in 180mL dichloromethane, 1.36mL (9.8mmol) trifluoroacetic anhydride was added dropwise below 20°C, and the reaction The mixture was stirred at room temperature for 3 h. Then 100 mL of water was added to the mixture, the organic layer was separated, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was subjected to flash column chromatography using silica gel 60 (0.015-0.040 mm) as adsorbent (Merck) and toluene:acetone = 2:1 as eluent to give after crystallization from 2-propanol 2.2 g (48.7% ) of the title compound. MS(EI)518.2(MH + ).

Embodiment 2

[0472] 3-methoxy-iso Azole-5-carboxylic acid (1-{4-[3-chloro-2-(2-methyl-2H-tetrazol-5-yl)- Indol-1-yl]-benzylcarbamoyl}-cyclopropyl)-amide

[0473] 0.16g (0.42mmol) 4-[3-chloro-2-(2-methyl-2H-tetrazol-5-yl)-indol-1-yl]-benzylamine hydrochloride (reference example 4) , 0.107g (0.47mmol) 1-[3-methoxy-iso Azole-5-carbonyl)-amino]-cyclopropanecarboxylic acid (P.D.O'Shea et al. J.Org.Chem. 2009, 74, 4547-4553), 0.15mL (1.07mmol) triethylamine, 0.192g (0.5 A mixture of mmol) HBTU and 5 mL of N,N-dimethylformamide was stirred at room temperature for 24 h, then concentrated in vacuo. The residue was subjected to flash column chromatography using silica gel 60 (0.015-0.040 mm) as adsorbent (Merck) and toluene:methanol = 4:1 as eluent to give 0.12 g (51.5%) of the title after crystallization from diethyl ether compound. MS(EI)548.1(MH + ).

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Abstract

The present invention relates to the indole derivatives of formula (I), wherein R1- R6 and X are defined in the claims and optical antipodes or racemates and / or salts thereof which are selective antagonists of bradykinin B1 to process for producing these compounds, pharmacological compositions containing them and to their use in therapy or prevention of painful and inflammatory conditions.

Description

field of invention [0001] The present invention relates to novel indole derivatives of formula (I) and their optical enantiomers or racemates and / or salts for use as selective bradykinin 1 antagonists. The invention also relates to methods of preparing such compounds. The invention further relates to pharmaceutical compositions comprising such compounds and the use of such compounds in methods for the treatment or prevention of disorders including pain and inflammation. The invention also provides methods for the manufacture of medicaments useful in the treatment or prevention of such conditions. Background of the invention [0002] Kinins are endogenous peptides formed after proteolytic cleavage of kininogen precursors by kallikrein in plasma and surrounding tissues (Bhoola, Pharmacol. Rev. 1992, 44, 1-80). Their biological effects are mediated through two G protein-coupled membrane receptors denoted B1 and B2. (Regoli and Barabe, Pharmacol. Rev. 1980, 32, 1-46, Marceau ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/04C07D403/14C07D413/12A61K31/404A61P29/00
CPCC07D403/04C07D403/14C07D413/12C07D413/14A61P1/04A61P13/12A61P17/00A61P17/02A61P19/00A61P19/02A61P19/06A61P21/00A61P25/00A61P27/02A61P29/00A61P43/00A61P9/00A61P9/10A61P3/10A61K31/41A61K31/404C07D209/42C07D401/14
Inventor G·贝凯G·A·贝涅伊I·博尔扎E·博佐S·福尔考什K·霍尔诺克A·帕普I·瓦高M·瓦什塔格
Owner RICHTER GEDEON NYRT
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