Triazine-aryl-bis-indoles and process for preparation thereof

Patent metadata

Field	Value
Publication number	US-9085559-B2
Application number	US-201013321445-A
Country	US
Kind code	B2
Filing date	Dec 31, 2010
Priority date	Jan 29, 2010
Publication date	Jul 21, 2015
Grant date	Jul 21, 2015

Abstract

A novel heterocyclic compound belonging to ‘triazine-aryl-bis-indoles’, useful for the treatment of asthma. The pathway by which this compound inhibits asthma is also demonstrated. The present invention also provides a process for the preparation of above compounds and their derivatives are presented.

First claim

We claim:

1. A triazine-aryl-bis-indole compound selected from one of:

2. The triazine-aryl-bis-indole compound of claim 1 , for the treatment of bronchial asthma comprising oral, mucosal or any other administration to a subject in need, said compound administered at a dose of about 1-20 μg/ml.

3. The triazine-aryl-bis-indole compound of claim 2 , wherein the compound inhibits PDE 4 activity in vitro and thereby shows inhibition of PDE-4 enzyme up to 73% taking rolipram as standard.

4. A process for preparation of a triazine-aryl-bis-indole compound of claim 1 wherein the process steps comprise:
a. reacting 2,4,6-trichloro-1,3,5-triazine (compound 9) with an amine in presence of a base at a temperature ranging between 0 to 40° C. for a period ranging between 1 to 2 hr to give the disubstituted chloro 1,3,5-triazine of formula A as shown below:

b. reacting the above disubstituted chloro 1,3,5-triazine with aromatic aldehyde in presence of a base at a temperature ranging between 50 to 70° C. for a period ranging between 4 to 6 hr to give the aryl ether of formula B as shown below:

reacting the triazine-aryl ethers with indole or indole-3-acetic acid in the presence of an acid at a temperature ranging between 50 to 60° C. for a period ranging between 6 to 8 hr to give the triazine-aryl-bis-indole of claim 1 .

5. The process for preparation of triazine-aryl-bis-indole compound of claim 4 wherein the amine is selected from an aliphatic amine or an aromatic amine.

6. The process for preparation of triazine-aryl-bis-indole compound of claim 4 , wherein the aromatic aldehydes is selected from vaniline or isovaniline.

7. A pharmaceutical composition comprising one or more Triazine-aryl-bis-indole compounds of claim 1 along with the pharmaceutically acceptable additives, carriers or diluents.

8. Method of treatment of bronchial asthma comprising administering one or more Triazine-aryl-bis-indole compounds of claim 1 by oral, mucosal and any other route to a subject in need at a dose ranging between 0.1 to 1 mg/kg BW.

9. The process of claim 5 wherein the aliphatic amine is cyclopropyl amine.

10. The process of claim 5 wherein the aromatic amine is aniline.

11. Method of treatment of bronchial asthma comprising administering to a subject in need by oral, mucosal, or any other route a Triazine-aryl-bis-indole compound of claim 1 at a concentration ranging from 10 μg/mL to 20 μg/mL, thereby showing PDE4 inhibition ranging from 16-73%.

Assignees

• Gangavaram Vasanta Madhava Sharma
• Yadav Jhillu Singh
• Palakodety Radha Krishna
• Bandyopadhyay Arun
• Roy Siddhartha
• Bandyopadhyay Santu
• Johri Rakesh Kamal
• Sharma Subhash Chander
• Ghosh Balaram
• Ulaganathan Mabalirajan
• Balwani Sakshi
• Paul Bholanath
• Saxena Ashok Kumar
• Council Scient Ind Res

Inventors

• Gangavaram Vasanta Madhava Sharma
• Yadav Jhillu Singh
• Palakodety Radha Krishna
• Bandyopadhyay Arun
• Roy Siddhartha
• Bandyopadhyay Santu
• Johri Rakesh Kamal
• Sharma Subhash Chander
• Ghosh Balaram
• Ulaganathan Mabalirajan
• Balwani Sakshi
• Paul Bholanath
• Saxena Ashok Kumar

Classifications

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• C07D251/50

  with a halogen atom attached to the third ring carbon atom · CPC title

• C07D251/52

  with an oxygen or sulfur atom attached to the third ring carbon atom · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title