Novel phenylpiperazine derivatives as dual cytokine regulators with TNF-α suppressing and IL-10 augmenting activity
| Autor: | Hiroshi Morimoto, Yoshiyuki Aoki, Tetsuko Fukuda, Tokushi Hanano, Yoichi Naka, Hiroshi Sumichika, Kunitomo Adachi, Masao Hisadome |
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| Rok vydání: | 2000 |
| Předmět: |
Central Nervous System
Lipopolysaccharides Stereochemistry medicine.medical_treatment Clinical Biochemistry Biological Availability Pharmaceutical Science Phenylpiperazine Pharmacology Biochemistry Piperazines Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Receptors Cytokine Molecular Biology Mice Inbred BALB C Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Drug candidate Septic shock Organic Chemistry medicine.disease Interleukin-10 Rats Interleukin 10 Cytokine chemistry Molecular Medicine Female |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 10:875-879 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(00)00128-1 |
| Popis: | Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-α suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k Scheme 2. Reagents and conditions: (a) Ac2O, NaOH, H2O, rt (87%); (b) cH2SO4, MeOH, reflux (72%); (c) LiAlH4, THF, 0 °C–rt (98%); (d) SOCl2, CHCl3, reflux (91%); (e) arylpiperazines, K2CO3, DMF, 80 °C (49–58%). Figure options Download full-size image Download high-quality image (32 K) Download as PowerPoint slide having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice, suggesting that 5k would be a promising drug candidate for the treatment of TNF-α associated diseases including septic shock. |
| Databáze: | OpenAIRE |
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