Synthesis and antiviral activity of some new bis-1,3-thiazole derivatives.
Treatment of 3-phenyl-1,3-thiazolidin-4-one derivative 1 with phenylisothiocyanate in DMF, in the presence of potassium hydroxide, at room temperature gave the non-isolable potassium salt 2. The in-situ reaction of 2 with differently substituted N-aryl hydrazonoyl chlorides 3, 7a-d and 14a-d afforded the corresponding 2-(pyrazolyl)thiazolylimino-5-(thiadiazolylidene)thiazolidin-4-one derivatives 6, 10a-d and 17a-d, respectively. Reaction of 2 with further α-haloketones yielded the 4-(pyrazolyl)thiazolylimino-bis-thiazolidine derivatives 22, 25 and 26. Single crystal X-ray analysis was used in structure elucidation of the products. The in-vitro antiviral screening against four viruses (Poliovirus, Influenza A (H1N1) virus, Hepatitis B virus and Hepatitis C virus) for the obtained compounds was examined. Structure activity relationship (SAR) was also studied. The goal of the work was achieved in discovering a very active compound 10a as anti HCV agent (EC50 0.56 μM).
Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt. Electronic address: dr_dawood@yahoo.com.
Kamal M
KM
Dawood
Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt.
Taha M A
TM
Eldebss
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
Heba S A
HS
El-Zahabi
Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt.
Mahmoud H
MH
Yousef
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D017955:Poliovirus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C000608196:5-(2-acetyl-4-phenyl-1,3,4-thiadiazol-5-ylidene)-2-(4-(2,3-dimethyl-1-phenyl-5-oxopyrazol-4-yl)thiazol-2-ylimino)-3-phenyl-1,3-thiazolidin-4-one; D000998:Antiviral Agents; D013830:Thiadiazoles; D013844:Thiazoles
1,3,4-Thiadiazole; 1,3-Thiazole; Antiviral activity; Pyrazole; SAR