Design, synthesis and evaluation of novel diaryl pyrrolopyrimidine and pyrrolothiazine derivatives as inhibitors of tumor necrosis factor stimulated gene-14 (TSG-14) production

Khalid M H Hilmy; Dalia H Soliman; Esmat B A Shahin; Hala S El-Deeb; Salah M El-Kousy

doi:10.1016/j.ejmech.2014.03.068

Design, synthesis and evaluation of novel diaryl pyrrolopyrimidine and pyrrolothiazine derivatives as inhibitors of tumor necrosis factor stimulated gene-14 (TSG-14) production

Eur J Med Chem. 2014 May 6:78:419-24. doi: 10.1016/j.ejmech.2014.03.068. Epub 2014 Mar 24.

Authors

Khalid M H Hilmy¹, Dalia H Soliman², Esmat B A Shahin³, Hala S El-Deeb⁴, Salah M El-Kousy⁴

Affiliations

¹ Department of Chemistry, Faculty of Science, Monufyia University, Shebin El-Kom, Egypt. Electronic address: hilmykhaled@yahoo.com.
² Pharmaceutical Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
³ Department of Biochemistry, Faculty of Medicine (Girls), Al-Azhar University, Cairo, Egypt.
⁴ Department of Chemistry, Faculty of Science, Monufyia University, Shebin El-Kom, Egypt.

PMID: 24704614
DOI: 10.1016/j.ejmech.2014.03.068

Abstract

A novel series of pyrrolothiazines 2-4 and pyrrolopyrimidines 5-7 have been synthesized. The structures of these compounds were established by spectroscopic and element microanalytical data. The newly synthesized compounds were evaluated as inhibitors of TSG-14. The most effective results were obtained by the S-sec-butyl derivatives 6e (80%) and the N-ethyl derivatives 4e (70%).

Keywords: Gene-14 (TSG-14); Pyrrolopyrimidines; Pyrrolothiazines; TNF-α.

MeSH terms

Animals
C-Reactive Protein / antagonists & inhibitors*
C-Reactive Protein / biosynthesis
Dose-Response Relationship, Drug
Drug Design*
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Male
Molecular Structure
Pyrimidines / administration & dosage
Pyrimidines / chemical synthesis
Pyrimidines / pharmacology*
Pyrroles / administration & dosage
Pyrroles / chemical synthesis
Pyrroles / chemistry
Pyrroles / pharmacology*
Rats
Serum Amyloid P-Component / antagonists & inhibitors*
Serum Amyloid P-Component / biosynthesis
Structure-Activity Relationship
Thiazines / chemical synthesis
Thiazines / chemistry
Thiazines / pharmacology*

Substances

1H-pyrrolo(1,2-c)(1,3)thiazine
Lipopolysaccharides
Pyrimidines
Pyrroles
Serum Amyloid P-Component
Thiazines
pyrrolopyrimidine
PTX3 protein
C-Reactive Protein