7757-21-3Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel molecules as potent PARP-1 inhibitors
Shen, Hui,Ge, Yiran,Wang, Junwei,Li, Hui,Xu, Yungen,Zhu, Qihua
, (2021/07/10)
Two series of novel compounds with inhibition activity against PARP-1 were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with high PARP-1 inhibition activity were selected to assess for cellular assays in vitro. Among them, compound II-4 displayed impressive results in both PARP-1 enzyme inhibition with IC50 value of 0.51 nM and anti-proliferation activity against HCT116 and HCC1937 cell lines with IC50 values of 6.62 nM and 12.65 nM, respectively. Also, II-4 exhibited good metabolic stability in vitro with t1/2 of 173.25 min and CLint of 0.04 mL/min/mg. Prediction of molecular properties and protein docking were applied to structure design. Our study provides potential lead compounds and design directions for the development of PARP-1 inhibitors.
PARP inhibitors containing phthalazin-1(2H)-one structure, and preparation method and medical application thereof
-
Paragraph 0047; 0048; 0049, (2019/02/04)
The invention relates to the field of medicinal chemistry, specifically to 4-(4-fluoro-3-(1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazinyl-2-carbonyl)benzyl)phthalazin-1(2H)-one derivatives (I). The formula I is as described in the specification, and R in the formula I is as defined in the specification. The invention also discloses a preparation method for the derivatives, and pharmaceutical compositions containing the derivatives. The results of pharmacodynamic tests prove that the derivatives of the invention have PARP inhibitory activity and can be used as a single therapeutic agent fortumors or be used in combination with other antitumor drugs, so the effects of improving the efficacy of conventional antitumor drugs and reducing the dosage and toxicity of conventional antitumor drugs are obtained.
Benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives as well as preparation method and application thereof
-
Paragraph 0057-0060, (2019/05/28)
The invention provides benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives and pharmaceutically acceptable salt, wherein the structure is as shown in a general formula I. The invention also discloses a preparation method of the benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives as well as the application of the benzo[4,5]imidazole[1,2-a]pyrazine ketone derivatives to the preparation of anti-tumor medicines and the preparation of PARP inhibitor medicines.
The systematic influence of tripodal ligands on the catechol cleaving activity of iron(III) containing model compounds for catechol 1,2-dioxygenases
Pascaly, Matthias,Duda, Mark,Schweppe, Florian,Zurlinden, Kristin,Mueller, Felizitas K.,Krebs, Bernt
, p. 828 - 837 (2007/10/03)
A series of mononuclear iron(III) complexes as functional and structural model compounds for intradiol cleaving catechol dioxygenases were synthesized. For all model compounds the iron(III) cores are in a distorted octahedral environment derived from tripodal tetradentate N4-donor ligands and a catechol. Model complexes for enzyme-substrate adducts were characterized by spectroscopic and electrochemical methods, and in four cases by single-crystal X-ray crystallography. The systematic variation of one ligand arm in the structurally characterized complexes yields a different steric shielding of the iron(III) center, significantly influencing the bonding of the catechol substrate and the subsequent reaction with dioxygen. The spectroscopic features and catechol cleaving activities of in situ generated complexes with the above ligands were probed. All complexes are highly reactive towards intradiol cleavage of various catechols in the presence of air. The catechol 1,2-dioxygenase reaction depends on the redox potential of both the iron(III) complex and the catechol derivative as well as the steric demand of the tripodal ligand. Some complexes show high catalytic activities with yields up to 84% with respect to aerial cleavage of catechols. The Royal Society of Chemistry 2001.
A Crown Ether Flavin Mimic: Synthesis and Properties of a Flavin Bearing a Crown Ring as a Recognition Site
Shinkai, Sheiji,Ishikawa, Yuichi,Shinkai, Hiroko,Tsuno, Takaharu,Makishima, Hiroki,et al.
, p. 1801 - 1808 (2007/10/02)
A crown ether flavin mimic (3,10-dimethyl-1',4',7',10',13',16'-hexaoxacyclooctadec-2'-enoisoalloxazine, crFl) which has within a molecule both flavin as a catalytic site and crown ring as a recognition site was synthesized.The absorption band and
