We are searching for new anti-inflammatory agents devoid of the limitations and side effects of the classical non steroidal anti-inflammatory drugs. Oxicams, like piroxicam, meloxicam or tenoxicam, represent a newer chemical category of the enolic acids, used in the treatment of chronic rheumatic diseases. In previous communications we reported the synthesis and anti-inflammatory evaluation of their pyridine-analogues. Some of them exhibited, depending on the substituents in position 2 and 3 pyridothiazines ring, anti-inflammatory, analgesic, antitumor and antioxidant action [1-5]. The pronounced biological action of the pyridothiazines stimulated us to continue our search and prepare their analogues, modified at the pyridine ring, in order to evaluate the influence of this structural change on biological activity.

A series of new 4-hydroxy-3-(4-substituted-benzoil)-2-[3-(4-(R₁-substituted-phenyl)-1-piperazinyl)propyl]-2H-benzo-1,2-thiazine 1,1-dioxides was synthesized starting from commercially available saccharine. Saccharine 1 was reacted with 4'-substituted-2-bromoacetophenone in N,N-dimethylformamide (DMF) to provide the N-alkylated product 2. Compound 2 on refluxing in sodium–ethanol resulted in ring expansion and formed cyclic sulfonamide 3. It was further alkylated with 4-(R₁-substituted-phenyl)-1-(3-chloropropyl)piperazine resulting in the corresponding coupled product 4.

The structure of the final products 4 was confirmed by elemental analysis and spectral analytical methods (IR, H¹NMR).

The newly obtained compounds were qualified for pharmacological tests in Jagiellonian University Medical College, Kraków, Poland.

References:

1. Toa Eiyo Kagaku Kogyo, pat. Jap., 8436685 (1984); C.A. 101, 7177a

2. Saito K., Okutani K.: Yakugaku Zasshi, 106 (1986) 1008; C.A. 107, 77727c

3. Zawisza T., Malinka W.: Farmaco 41 (1986) 892

4. Malinka W., Kaczmarz M., Filipek B., Sapa J., Głód B.: Farmaco 57 (2002) 737

5. Malinka W., Kaczmarz M., Redzicka A.: Acta Pol. Pharm. Drug Res. 61 (2004) 100

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/25472 must be provided.

1. Effect of the new derivatives of oxicams on efflux pumps overexpressed in resistant human colorectal adenocarcinoma cell line
2. Synthesis of new piroxicam derivatives and their influence on lipid bilayers
3. The interaction of new Piroxicam analogues with lipid bilayers – a calorimetric and fluorescence spectroscopic study
4. New Mannich bases of N-substituted 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones and their biological properties
5. The interaction of new fluphenazine analogues with lipid membrane
6. New isothiazolopyridines and their in vitro antibacterial activity
7. The influence of fluphenazine and its newly synthesized derivatives on the properties of liposomal membranes
8. PYRIDO-1,2-THIAZINES AND THEIR IN VITRO ANITBACTERIAL EVALUATION
9. A STRUCTURAL AND SAR STUDY OF 2-[4-(SUBSTITUTED-PHENYL)PIPERAZIN-1-YLMETHYL]ISOTHIAZOLO[5,4-b]PYRIDINES WITH ANALGESIC ACTIVITY.