2166-31-6Relevant articles and documents
Synthesis, Characterization and Solubility Determination of 6-Phenyl-pyridazin-3(2H)-one in Different Pharmaceutical Solvents
Shakeel, Faiyaz,Imran, Mohd,Haq, Nazrul,Alshehri, Sultan,Khalid Anwer
, (2019)
The current research work proposed the solubility data and solution thermodynamic properties of the cardiovascular agent 6-phenylpyridazin-3(2H)-one [PPD] in twelve pharmaceutical solvents at “T = 298.2 K to 318.2 K” and “p = 0.1 MPa”. The measured solubilities of PPD were regressed well with “van’t Hoff and Apelblat models”. The solid phases of pure and equilibrated PPD were characterized using differential scanning calorimetry and powder X-ray differactometry, and the results suggested no transformation of PPD into solvates/hydrates/polymorphs after equilibrium. The solubilities of PPD in a mole fraction at “T = 318.2 K” were noted at a maximum in dimethyl sulfoxide (DMSO, 4.73 × 10?1), followed by polyethylene glycol-400 (PEG-400, 4.12 × 10?1), Transcutol (3.46 × 10?1), ethyl acetate (EA, 81 × 10?2), 2-butanol (2.18 × 10?2), 1-butanol (2.11 × 10?2), propylene glycol (PG, 1.50 × 10?2), isopropyl alcohol (IPA, 1.44 × 10?2), ethylene glycol (EG, 1.27 × 10?2), ethanol (8.22 × 10?3), methanol (5.18 × 10?3) and water (1.26 × 10?5). Similar tendencies were also noted at other studied temperatures. The results of the “apparent thermodynamic analysis” showed an endothermic and entropy-driven dissolution of PPD in all pharmaceutical solvents. The results of the activity coefficients suggested a maximum interaction at the molecular level in PPD-DMSO, PPD-PEG-400 and PPD-Transcutol, compared with other combination of the solute and solvents.
Development of pyridazine derivatives as potential EGFR inhibitors and apoptosis inducers: Design, synthesis, anticancer evaluation, and molecular modeling studies
Ahmed, Marwa F.,Santali, Eman Y.,Mohi El-Deen, Eman M.,Naguib, Ibrahim A.,El-Haggar, Radwan
, (2020/11/27)
Novel hybrids of pyridazine-pyrazoline were synthesized aiming to develop new antiproliferative candidates. All compounds were submitted to the National Cancer Institute (NCI), USA, and many were proved to have significant antiproliferative activity. In addition, in vitro studies of the epidermal growth factor receptor (EGFR) inhibition showed that compounds IXn, IXg, IXb and IXl exhibited excellent inhibitory effect (IC50 = 0.65, 0.75, 0.82 and 0.84 μM, respectively) compared to Erlotinib (IC50 = 0.95 μM). The mechanistic effectiveness in cell cycle progression, apoptotic induction and gene regulation were assessed for the promising compounds IXg and IXn due to their significant EGFR inhibition. Flow cytometeric analysis indicated that compounds IXg and IXn result in increased cell numbers in phase G2/M, suggesting cell cycle arrest in phase G2/M in UO-31cells. Furthermore, real time PCR assay illustrated that compounds IXg and IXn elevated Bax/Bcl2 ratio which confirmed the mechanistic pathway of them. Moreover, the apoptotic induction of UO-31 renal cancer cells was enhanced effectively through activation of caspase-3 by compounds IXg and IXn. On the other hand, molecular docking study was performed to investigate binding mode of interaction of compounds with EGFR-PK in the active site with the aim of rationalizing its promising inhibitory activity. Finally, based on the aforementioned findings, compounds IXg and IXn could be considered as effective apoptosis modulators and promising leads for future development of new anti-renal cancer agents.
Synthesis of novel N-substitutedphenyl-6-oxo-3-phenylpyridazine derivatives as cyclooxygenase-2 inhibitors
Khan, Abida,Diwan, Anupama,Thabet, Hamdy K,Imran, Mohd
, p. 573 - 584 (2020/03/23)
Some novel non-ulcerogenic N-substitutedphenyl-6-oxo-3-phenylpyridazines as COX-2 inhibitors have been developed (Supplementary material Appendix 1). The novel aldehyde 3 was prepared by reacting 6-phenylpyridazin-3(2H)-one with 4-fluorobenzaldehyde. The aldehyde 3 was reacted with different hydrazines and thiazolidin-4-ones to obtain the novel N-substitutedphenyl-6-oxo-3-phenylpyridazine derivatives. These were assessed for their anti-inflammatory potential and gastric ulcerogenic effects. The molecular docking investigations were also undertaken. The spectroscopic data were coherent with the allocated structures of the compounds. The compounds 4a (IC50 = 17.45 nm; p 50 = 17.40 nm; p 50 = 16.76 nm; p 50 = 17.15 nm; p 50 = 17.79 nm; p .05). These findings were consistent with the molecular docking investigations of 4a, 4b, 5a, and 10. The in vivo anti-inflammatory profile of 4a, 4b, 5a, and 10 was also superior to celecoxib and indomethacin. The compounds 4b, 5a, and 10 revealed no gastric ulcerogenic effects, wherein the compound 4a produced almost negligible gastric ulcerogenic effects than celecoxib and indomethacin. The compounds 4a, 4b, 5a, and 10 have been postulated as promising non-ulcerogenic COX-2 inhibitors.
