87235-61-8Relevant academic research and scientific papers
Design and synthesis of novel pyrrolo[2,3-b]pyridine derivatives targeting V600EBRAF
Abdel-Maksoud, Mohammed S.,Ali, Eslam M. H.,Ammar, Usama M.,Mersal, Karim I.,Oh, Chang-Hyun,Yoo, Kyung Ho
, (2020/04/28)
Several pyrrolo[2,3-b]pyridine-based B-RAF inhibitors are well known and some of them are currently FDA approved as anticancer agents. Based on the structure of these FDA approved V600EB-RAF inhibitors, two series of pyrrolo[2,3-b]pyridine scaffold were designed and synthesized in attempt to develop new potent V600EB-RAF inhibitors. The 38 synthesized compounds were biologically evaluated for their V600EB-RAF inhibitory effect at single dose (10 μM). Compounds with high percent inhibition were tested to determine their IC50 over V600EB-RAF. Compounds 34e and 35 showed the highest inhibitory effect with IC50 values of 0.085 μM and 0.080 μM, respectively. Headed for excessive biological evaluation, the synthesized derivatives were tested over sixty diverse human cancer cell lines. Only compound 35 emerged as a potent cytotoxic agent against different panel of human cancer cell lines.
Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold
Abdel-Maksoud, Mohammed S.,Ammar, Usama M.,Oh, Chang-Hyun
, p. 2041 - 2051 (2019/04/05)
In this work, a new series of imidazo[2,1-b]thiazole was designed and synthesized. The new compounds are having 3-fluorophenyl at position 6 of imidazo[2,1-b]thiazole and pyrimidine ring at position 5. The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. The final compounds were selected by NCI for in vitro cytotoxicity screening. Most derivatives showed cytotoxic activity against colon cancer and melanoma cell lines. In addition, IC50s of the target compounds were determined over A375 and SK-MEL-28 cell lines using sorafenib as positive control. Compounds12b, 12c, 12e, 12f, 15a, 15d, 15f, 14g and 15h exhibited superior activity when compared to sorafenib. The most potent compounds were tested against wild type BRAF, v600e BRAF, and CRAF. Compound 15h exhibited a potential inhibitory effect againstV600EBRAF (IC50 = 9.3 nM).
Design, synthesis and biological evaluation of lazabemide derivatives as inhibitors of monoamine oxidase
Zhou, Shiyang,Chen, Guangying,Huang, Gangliang
, p. 4863 - 4870 (2018/08/27)
In the studied a series novel of lazabemide derivatives were designed, synthesized and evaluated as inhibitors of monoamine oxidase (MAO-A or MAO-B). These compounds used lazabemide as the lead compound, and the chemistry structures were modified by used the bioisostere and modification of compound with alkyl principle. The two types of inhibitors (inhibition of MAO-A and inhibition of MAO-B) were screened by inhibition activity of MAO. In vitro experiments showed that compounds 3a, 3d and 3f had intensity inhibition the biological activity of MAO-A, while compounds 3i and 3m had intensity inhibition the biological activity of MAO-B. It could be seen from the data of inhibition activity experiments in vitro, that the compound 3d was IC50 = 3.12 ± 0.05 μmol/mL of MAO-A and compound 3m was IC50 = 5.04 ± 0.06 μmol/mL. In vivo inhibition activity experiments were conducted to evaluate the inhibitory activity of compounds 3a, 3d, 3f, 3i and 3m by detecting the contents of 5-HT, NE, DA and activity of MAO-A and MAO-B in plasma and brain tissue. In vivo inhibition activity evaluation results showed that the compounds 3a, 3d, 3f, 3i and 3m had increased the contents of 5-HT, NE and DA in plasma and brain tissues. Meanwhile, the determination results activity of MAO in plasma and brain tissue showed that the compounds 3a, 3d, and 3f had a significant inhibitory effect on the activity of MAO-A, while the compounds 3i and 3m showed inhibitory effect on the activity of MAO-B. This study provided a new inhibitors for inhibiting of MAO activity.
Study of synthesis and cardiovascular activity of some furoxan derivatives as potential NO-donors
Mu, Li,Feng, Si-Shen,Go, Mei Lin
, p. 808 - 816 (2007/10/03)
A series of hybrid molecules incorporating the furoxan and nicorandil moieties were designed as potential NO donors with cardiovascular and cerebrovascular activities. Thirty-six target molecules were successfully synthesized by conventional methods and characterized by infrared spectroscopy, 1H-NMR spectroscopy and high resolution mass spectra. The compounds were tested for their effects on KCl-induced contraction of rabbit thoracic aorta whose endothelium was denuded. Eight compounds were found to reduce KCl-induced contraction by more than 30% at 10 μM. All except one of these compounds are characterized by the presence of electron withdrawing groups in the phenyl ring attached via an amide or ester linkage to the furoxan moiety. The nature of the terminal carbonyl linkage (ester or amide) and the length or type of the alkyl chain bridging the two carbonyl functions have little effect on the activity. One of the active compounds, N-(4- methoxy-benzoyl)-N'-[3-methylfuroxanyl-4-carbonyl)piperazine (17i) was tested for hypotensive effects on anaesthetized rats at 1.5 mg/kg, and found to demonstrate a gradual and sustained hypotensive effect. The results suggest that the furoxannicorandil derivatives are a useful lead in the design of NO- donor compounds for hypertension.
BENZAMIDE DERIVATIVES
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, (2008/06/13)
Benzamides of the formula I wherein R1 and R2 each independently is hydrogen, halogen, lower alkyl, lower alkoxy, cyano, trifluoromethyl, sulfamoyl, mono(lower alkyl)sulfamoyl or di(lower alkyl)sulfamoyl or R1 and R2 on adjacent carbon atoms together are
